Malaysian Statistics on Medicines 2015-2016

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MALAYSIAN STATISTICS ON MEDICINES 2015-2016

Edited by

Mary Chok Chiew Fong, Azzy Iyzati Ahmad Shanizza

A publication of the

Pharmaceutical Services Programme Ministry of Health Malaysia

February 2020 Ministry of Health Malaysia

Published by Pharmaceutical Services Programme Ministry of Health Malaysia Lot 36, Jalan Universiti, 46200 Petaling Jaya, Selangor, Malaysia.

Telephone (603) 7841 3200 Fax (603) 7968 2222 Website www.pharmacy.gov.my

This report is copyrighted. Reproduction and dissemination of this report in part or in whole for research, educational or other non-commercial purposes are authorised without any prior written permission from the copyright holders provided the source is fully acknowledged.

Suggested citation: Malaysian Statistics on Medicines 2015-2016; Pharmaceutical Services Programme, Ministry of Health Malaysia: Kuala Lumpur, 2020.

Funding : The study on medicines utilisation and publication of Malaysian Statistics on Medicines were funded by Pharmaceutical Services Programme, Ministry of Health Malaysia.

PREFACE

Enhance the accessibility of affordable and equitable medicines, and promote rational use of safe and effective medicines in Malaysia are integral of the implementation of Malaysian National Medicines Policy (NMP). Govern by the policy, it is therefore essential to deliver pharmaceutical services of high quality and efficiency to the nation as a single entity by all stakeholders, irrespective of either in public or private sector to improve health status and quality of life of Malaysian population. Thus, Pharmaceutical Services Programme has been the pioneer in conducting several initiatives to achieve the ultimate goals of NMP. National medicines utilisation study and publication of Malaysian Statistics on Medicines (MSOM) are example of these initiatives to support NMP. Most current, up-to-date findings in MSOM may serve as valuable resources for better decision making in areas of higher priority or unmet needs and financial concerns in healthcare system.

Since the release of MSOM 2011-2014 in 2018, considerable effort has been taken in improving the methodology of medicines utilisation study in the subsequent years of study. This including the formation of a technical advisory committee, a platform designated for discussion and sharing of information and experiences. In addition, methods on data collection and processing has been revised and improved further to acquire high quality data. This is crucial for the publication of current, accurate and reliable statistics on time for use by health professionals. In this report, the tabulation of findings was further refined by including groups of medicines which was not previously included in MSOM 2011-2014. For the purpose of enabling meaningful comparison with statistics published in the past, same analysis method was applied.

We sincerely hope that MSOM 2015-2016 would provide valuable information to all fields of healthcare professionals, and could serve as a source of reference and baseline for embarking in future research or clinical audits towards promoting rational prescribing and effective medicines use.

We are grateful to all colleagues and collaborators who had worked very hard in ensuring the success of this report. These including all agencies, institutions, expert panel members and all individuals who had contributed invaluable input. In the spirit of true cooperation and partnership in research and development, the value of rational use of medicines and attaining high quality healthcare status of the nation can be uphold.

Pharmaceutical Services Programme Ministry of Health Malaysia

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ACKNOWLEDGEMENTS

Team members of national medicines utilisation study would like to express highest gratitude to all the individuals involved, directly or indirectly in making the study on medicines utilisation and publication of MSOM 2015-2016 a success. This gratitude would go to

. Senior Director of Pharmaceutical Services Programme, Ministry of Health Malaysia for the invaluable support in conducting research,

. Director of Pharmacy Policy and Strategic Planning Division, Ministry of Health Malaysia for the support in providing resources and advice on implementing medicines utilisation study and publication of this report,

. Deputy Director and pharmacists at Medicines Pricing Branch, Pharmacy Practice and Development Division, Ministry of Health Malaysia, of their generosity in data sharing required for this project,

. Deputy Director and pharmacists at Pharmacy Logistics Branch, Pharmacy Practice and Development Division, Ministry of Health Malaysia, of the precious,

. Personnel at Pharmaniaga Logistics Sdn Bhd, who had contributed diligently to the study,

. IQVIA Solution Malaysia Sdn Bhd, for the valuable inputs,

. All the members of the expert panel who had contributed to the review and writing of this report,

. All participating pharmacist personnel at Pharmacy Departments in Ministry of Health Malaysia, and at three university hospitals in the Ministry of Education Malaysia,

. Reviewers and members of Technical Advisory Committee for their extensive review and valuable comments on the project and report,

. All individuals who had in one way or another contributed enthusiastically to the success of this project.

Lastly, the team would like to thank the Director General of Health Malaysia for the permission to publish this report.

Project Team of National Medicines Utilisation Study

Leader Dr. Azuana Ramli Deputy Director Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Coordinator Mr. Tineshwaran Velvanathan Pharmacist Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Mdm Azzy Iyzati Ahmad Shanizza Research Officer Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Mdm Chan Lai Yue Pharmacist Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Statistician Ms. Mary Chok Chiew Fong Pharmacist Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Research Assistant Ms. Safura Sa’ad Research Officer Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Ms. Noor Atiqah Mat Yusoff Research Officer Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Mr. Mohd Faiz Abdul Manan Research Officer Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Reviewers of Malaysian Statistics on Medicines 2015-2016

Mdm Norazlin A. Kadir Pharmacist Pharmacy Practice and Development Division Ministry of Health Malaysia

Mdm Hazimah Hashim Pharmacist Pharmacy Practice and Development Division Ministry of Health Malaysia

Mdm. Haarathi Chandriah Pharmacist Pharmacy Practice and Development Division Ministry of Health Malaysia

Technical Advisory Committee of National Medicines Utilisation Study

Chairperson Dr. Hasenah Ali Director Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Co-chairperson Dr. Roshayati Mohamad Sani Director Pharmacy Practice and Development Division Ministry of Health Malaysia

Secretary Dr. Azuana Ramli Deputy Director Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Member Mdm Nur’Ain Shuhaila Shohaimi Deputy Director Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Mdm Wan Utma Sapini Wan Abdul Samad Pharmacist Pharmacy Practice and Development Division Ministry of Health Malaysia

Mdm Norazlin A. Kadir Pharmacist Pharmacy Practice and Development Division Ministry of Health Malaysia

Mdm Rosliza Lajis Pharmacist Pharmacy Practice and Development Division Ministry of Health Malaysia

Ms. Nor Hasni Haron Pharmacist Pharmacy Practice and Development Division Ministry of Health Malaysia

Ms. Teoh Iyinh Theng Pharmacist Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

Members of Expert Panel

CARDIOLOGY

Dr. Abd Kahar Abd Ghapar Dr. Amin Ariff Nuruddin Head of Department & Senior Consultant Senior Consultant Cardiologist Cardiologist National Heart Institute Serdang Hospital

Dr. Azhari Rosman Prof Dr. Omar Ismail Senior Consultant Cardiologist Consultant Cardiologist National Heart Institute Universiti Islam Antarabangsa Sultan Abdul Halim Mu’adzam Shah

Prof Dr. Wan Azman Wan Ahmad Dr. Wardati Mazlan Kepli Consultant Cardiologist Pharmacist University Malaya Medical Centre Serdang Hospital

Mdm Nirmala Jagan Mr. Jivanraj Nagarajah Pharmacist Pharmacist Kuala Lumpur Hospital Kuala Lumpur Hospital

DERMATOLOGY

Dr. Suganthi Thevarajah Dr. Preamala Gunabalasingam Head of Department & Senior Consultant Head of Department & Consultant Dermatologist Dermatologist Kuala Lumpur Hospital Melaka Hospital

Dr. Tang Min Moon Consultant Dermatologist Kuala Lumpur Hospital

ENDOCRINOLOGY

Dr. Zanariah Hussein Dr. Nor Afidah Karim Senior Consultant Endocrinologist & Physician Endocrinologist & Physician Putrajaya Hospital Tuanku Ja’afar Hospital, Seremban

Dr. Vijiya Mala Valayatham Dr. Danish Ng Ooi Yee Endocrinologist & Physician Endocrinologist & Physician Putrajaya Hospital Selayang Hospital

Dr. Wong Hui Chin Dr. Navin Kumar Loganadan Endocrinologist & Physician Pharmacist Tengku Ampuan Rahimah Hospital, Klang Putrajaya Hospital

Mdm Daphne Gima Pharmacist Putrajaya Hospital

GASTROENTEROLOGY AND HEPATOLOGY

Dr. Rosaida Md Said Dr. Tan Soek Siam Senior Consultant Gastroenterologist & Senior Consultant Gastroenterologist & Hepatologist Hepatologist Ampang Hospital Selayang Hospital

Dr. Muhammad Radzi Abu Hassan Dr. Zalwani Zainuddin Senior Consultant Gastroenterologist & Consultant Gastroenterologist & Hepatologist Hepatologist Sultanah Bahiyah Hospital, Alor Setar Sultanah Bahiyah Hospital, Alor Setar

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Dr. Norasiah Abu Bakar Consultant Gastroenterologist & Hepatologist Raja Perempuan Zainab II Hospital, Kota Bharu

HAEMATOLOGY

Dr. Jameela Sathar Head of Department & Consultant Haematologist Ampang Hospital

IMMUNIZATION/VACCINE

Dr. Rohani Jahis Dr. Jamiatul Aida Md Sani Head of Section (Zoonosis Control) Public Health Specialist Disease Control Division Disease Control Division Ministry of Health Malaysia Ministry of Health Malaysia

Mdm Najwa Ahmad Hamdi Pharmacist Public Health Development Division Ministry of Health Malaysia

INFECTIOUS DISEASES

Dr. Leong Chee Loon Dr. Steven Lim Chee Loon Infectious Disease Consultant Physician Infectious Disease Specialist Kuala Lumpur Hospital Raja Permaisuri Bainun Hospital, Ipoh

Dr. Rahela Ambaras Khan Mdm Hannah Md Mahir Pharmacist Pharmacist Kuala Lumpur Hospital Sungai Buloh Hospital

Mdm Mak Woh Yon Mdm Preethi Raghavan Pharmacist Pharmacist Kuala Lumpur Hospital Sungai Buloh Hospital

NEUROLOGY

Dr. Zariah Abdul Aziz Dr. Sapiah Sapuan Senior Consultant Neurologist Consultant Neurologist Sultanah Nur Zahirah Hospital, Kuala Sungai Buloh Hospital Terengganu

Dr. Tee Sow Kuan Dr. Puvanarajah Santhi Neurologist Neurologist Kuala Lumpur Hospital Kuala Lumpur Hospital

Mdm Norsima Nazifah Sidek Mdm Tan Ai Leen Pharmacist Pharmacist Sultanah Nur Zahirah Hospital, Kuala Kuala Lumpur Hospital Terengganu

OBSTETRIC AND GYNECOLOGY

Dr. Norashikin Abdul Fuad Dr. Nasuha Yaacob Head of Department & Obstetrician & Obstetrician & Gynaecologist Gynaecologist Sultanah Nur Zahirah Hospital, Kuala Sungai Buloh Hospital Terengganu

Dr. Haliza Kamarudin Mdm Vanessa Liang Lu Wen Obstetrician & Gynaecologist Pharmacist Women and Children Hospital, Kuala Lumpur Women and Children Hospital, Kuala Lumpur

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ONCOLOGY

Dr. Ros Suzanna Ahmad Bustaman Dr. Tan Chih Kiang Head of Department & Consultant in Clinical Oncologist Radiotherapy & Oncology National Cancer Institute Kuala Lumpur Hospital

Dr. Prathepamalar Yehgambaram Ms. Nik Nuradlina Nik Adnan Clinical Oncologist Pharmacist Kuala Lumpur Hospital National Cancer Institute

Ms. Lee Mei Wah Pharmacist Kuala Lumpur Hospital

OPHTHALMOLOGY

Dr. Shamala Retnasabapathy Dr. Jamalia Rahmat Head of Department & Consultant Head of Department & Consultant Ophthalmologist Ophthalmologist Sungai Buloh Hospital Kuala Lumpur Hospital

Dr. Vanitha Ratnalingan Consultant Ophthalmologist Sungai Buloh Hospital

ORTHOPAEDIC

Dr. Fazir Mohamad Head of Department & Consultant in Orthopaedic Surgery Kuala Lumpur Hospital

OTORHINOLARYNGOLOGY

Dr. Siti Sabzah Mohd Hashim Dr. Abd Razak Ahmad National Head of Otorhinolaryngology Services National Head and Neck Sub-Specialist Advisor, & Senior Consultant in Otorhinolaryngology Head of Department & Senior Consultant in Sultanah Bahiyah Hospital, Alor Setar Otorhinolaryngology Melaka Hospital

Dr. Zulkiflee Salahuddin Dr. Iskandar Hailani Deputy National Head of Otorhinolaryngology Head of Department & Senior Consultant in Services & Senior Consultant in Otorhinolaryngology Otorhinolaryngology Kuala Lumpur Hospital Raja Perempuan Zainab II Hospital, Kota Bharu

Dr. Jothi Shanmuganathan Dr. Amran Mohamad Head of Department & Senior Consultant in Senior Consultant in Otorhinolaryngology Otorhinolaryngology Sultanah Nur Zahirah Hospital, Kuala Sultanah Aminah Hospital, Johor Bahru Terengganu

Dr. Halimuddin Sawali Mr. Leow Wooi Leong Head of Department & Consultant in Pharmacist Otorhinolaryngology Kuala Lumpur Hospital Queen Elizabeth Hospital, Kota Kinabalu

PHARMACOECONOMIC

Mdm Wan Utma Sapini Wan Abdul Samad Mdm Rosliza Lajis Pharmacist Pharmacist Pharmacy Practice and Development Division Pharmacy Practice and Development Division Ministry of Health Malaysia Ministry of Health Malaysia

Mdm Nazatul Syima Idrus Mr. Muhammad Md Zain Pharmacist Pharmacist Pharmacy Practice and Development Division Pharmacy Practice and Development Division Ministry of Health Malaysia Ministry of Health Malaysia

Mr. Tineshwaran Velvanathan Pharmacist Pharmacy Policy and Strategic Planning Division Ministry of Health Malaysia

PSYCHIATRY

Dr. Norharlina Bahar Dr. Chin Loi Fei Consultant Psychiatrist Consultant Psychiatrist Selayang Hospital Sungai Buloh Hospital

Dr. Azizul Awaluddin Dr. Noormazita Mislan Consultant Psychiatrist Consultant Psychiatrist Putrajaya Hospital Tuanku Ja’afar Hospital, Seremban

RESPIRATORY

Dr. Nabilah Salman Parasi @ Sulaiman Dr. Mona Zaria Nasaruddin Consultant Pulmonologist Consultant Pulmonologist Institute of Respiratory Medicine Serdang Hospital

Mdm Liew Mei Yao Pharmacist Serdang Hospital

RHEUMATOLOGY

Dr. Gun Suk Chyn Dr. Mollyza Mohd Zain Head of Department & Medical Consultant in Medical Consultant in Rheumatology Rheumatology Selayang Hospital Tuanku Ja’afar Hospital, Seremban

Dr. Liza Mohd Isa Dr. Chong Hwee Cheng Medical Consultant in Rheumatology Medical Consultant in Rheumatology Putrajaya Hospital Melaka Hospital

Mdm Siti Rabiatul Adawiyah Pharmacist Tuanku Ja’afar Hospital, Seremban

UTILISATION OF MEDICINES

Mdm Rozita Mohamad Dr. Rosliana Rosli Deputy Director Pharmacist Pharmacy Practice and Development Division Pharmacy Practice and Development Division Ministry of Health Malaysia Ministry of Health Malaysia

Mdm Yusmiza Azmi Ms. Sarahfarina Abdul Rahim Pharmacist Pharmacist Pharmacy Practice and Development Division Pharmacy Practice and Development Division Ministry of Health Malaysia Ministry of Health Malaysia

Mdm Azzy Iyzati Ahmad Shanizza Ms. Mary Chok Chiew Fong Research Officer Pharmacist Pharmacy Policy and Strategic Planning Pharmacy Policy and Strategic Planning Division Division Ministry of Health Malaysia Ministry of Health Malaysia

ABBREVIATIONS

ACE angiotensin converting enzyme LARC long-acting reversible contraceptive ACIP Advisory Committee on LDL-c low density lipoprotein cholesterol Immunisation Practice MDR multidrug resistant ACTH adrenocorticotropic hormone MMR measles-mumps-rubella ADHD attention deficit hyperactive MNHA Malaysia National Health Accounts disorder MoE Ministry of Education Malaysia AED antiepileptic drug MoH Ministry of Health Malaysia AMS antimicrobial stewardship MoHMF Ministry of Health Medicines ARB angiotensin II receptor blocker Formulary ART assisted reproductive technology MRSA methicillin-resistant Staphylococcus ATC anatomical therapeutic chemical aureus BCG bacille Calmette-Guerin MSOM Malaysian Statistics on Medicines CNS central nervous system NCD non-communicable disease COPD chronic obstructive pulmonary NHMS National Health and Morbidity disease Survey CRE carbapenem-resistant NIP National Immunisation Programme enterobacteriaceae NMP National Medicines Policy CVD cardiovascular disease NMUS National Medicines Use Survey DAA direct-acting antiviral OECD Organisation of Economic DALY disability-adjusted life year Cooperation and Development DDD defined daily dose OHSS ovarian hyperstimulation syndrome DG Director General OPV oral polio vaccine DOAC direct oral anticoagulant OSCC one stop crisis centre DPP-4 dipeptidyl peptidase-4 OTC over-the-counter EGFR epidermal growth factor receptor PBS Pharmaceutical Benefits Scheme ESBL extended-spectrum beta- PCI percutaneous coronary intervention lactamases PCV pneumococcal conjugated FDA Food and Drug Administration vaccine FDC fixed-dose combination PPH postpartum haemorrhage FET frozen-thaw embryo transfer PPI proton-pump inhibitor GDP gross domestic product PSP Pharmaceutical Services GLP-1 glucagon-like peptide-1 Programme GORD gastro-oesophageal reflux disease PUD peptic ulcer disease GVAP Global Vaccine Action Plan SABA short-acting β2 adrenoreceptor H2RA H2-receptor antagonist agonists HIV human immunodeficiency virus SGLT-2 sodium-glucose co-transporter 2 HMG CoA β-hydroxy β-methylglutaryl- SIA supplementary immunisation coenzyme A activities HPV human papilloma virus SSRI selective serotonin reuptake ICS inhaled corticosteroid inhibitor IVF in-vitro fertilization TB tuberculosis JE Japanese encephalitis TEH total expenditure on health LABA long-acting β2 adrenoreceptor TNF-α tumour necrosis factor alpha agonists WHO World Health Organisation

CONTENTS

Preface iii Acknowledgements iv Project Team of National Medicines Utilisation Study v Reviewers of Malaysian Statistics on Medicines 2015-2016 v Technical Advisory Committee of National Medicines Utilisation Study vi Members of Expert Panel vii Abbreviations xi

1 Study on Medicines Utilisation in Malaysia 1

2 Utilisation of Medicines in Malaysia 5

3 Expenditures on Medicines in Malaysia 13

4 Alimentary Tract and Metabolism 18 4.1 Statistics on medicines for alimentary tract and metabolism 18 4.2 Utilisation of drugs for alimentary disorders 27 4.3 Utilisation of antiobesity drugs 28 4.4 Utilisation of antidiabetic drugs 28

5 Medicines for Blood and Blood Forming Organs 30 5.1 Statistics on medicines for blood and blood forming organs 30

6 Cardiovascular System 33 6.1 Statistics on medicines for cardiovascular system 33 6.2 Utilisation of drugs for cardiovascular disorders 40 6.3 Utilisation of drugs for hypertension 41 6.4 Utilisation of lipid modifying drugs 42

7 Dermatologicals 44 7.1 Statistics on dermatological preparations 44 7.2 Utilisation of dermatological preparations 48

8 Genito Urinary System and Sex Hormones 50 8.1 Statistics on medicines for genito urinary system and sex hormones 50 8.2 Utilisation of gynecologicals, sex hormones and hormonal contraception 54

9 Systemic Hormonal Preparations, excluding Sex Hormones and Insulins 56 9.1 Statistics on systemic hormonal preparations, excluding sex hormones and 56 insulins 9.2 Utilisation of systemic hormonal preparations 59 9.3 Utilisation of systemic glucocorticoids in rheumatology 60

10 Antiinfectives for Systemic Use 61 10.1 Statistics on antiinfectives for systemic use 61 10.2 Utilisation of systemic antiinfectives 76 10.3 Utilisation of drugs for viral hepatitis C 77 10.4 Utilisation of vaccines 77

11 Antineoplastic and Immunomodulating Agents 80 11.1 Statistics on antineoplastic and immunomodulating agents 80 11.2 Utilisation of antineoplastic agents, targeted therapy and endocrine therapy 89 11.3 Utilisation of immunosuppressive agents in rheumatology 90

12 Musculo-Skeletal System 91 12.1 Statistics on medicines for musculo-skeletal system 91

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13 Nervous System 96 13.1 Statistics on medicines for nervous system 96 13.2 Utilisation of drugs for neurological disorders 102 13.3 Utilisation of drugs for psychiatric disorders 104

14 Antiparasitic Products 106 14.1 Statistics on antiparasitic products 106 14.2 Utilisation of antimalarials 110

15 Respiratory System 111 15.1 Statistics on medicines for respiratory system 111 15.2 Utilisation of antihistamines and nasal decongestants 118 15.3 Utilisation of drugs for obstructive airway diseases 118

16 Sensory Organs 120 16.1 Statistics on medicines for sensory organs 120 16.2 Utilisation of ophthalmological agents 125 16.3 Utilisation of otological agents 126

17 Various Therapeutic Products 127 17.1 Statistics on other therapeutic products 127

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Study on Medicines Utilisation In Malaysia Mary Chok Chiew Fong, Azzy Iyzati Ahmad Shanizza, Tineshwaran Velvanathan, Azuana Ramli 1

AN OVERVIEW

Study on Medicines Utilisation and National Medicines Policy

Study on medicines utilisation in Malaysia is an initiative by Pharmaceutical Services Programme (PSP) at the Ministry of Health Malaysia (MoH). This initiative is fundamental to support and augment the implementation of National Medicines Policy (NMP), in which the aim is to promote equitable access and rational use of safe, effective and affordable medicines, and ultimately lead to the improvement in quality of health for all Malaysians.

Study on Medicines Utilisation, National Medicines Use Survey and Malaysian Statistics on Medicines

Malaysian Statistics on Medicines (MSOM) is a publication reporting the findings of a nationwide study on medicines utilisation. Since the first publication for the year 2004, study methodology had progressively advanced and improved. When it was first started, it was named National Medicines Use Survey (NMUS) and the study relied heavily on nationwide survey to project medicines utilisation for Malaysian population, particularly in the private sector. Over the years, through partnership with a private company, data on procurement and sales of medicines by public and private sector were vastly available and acquired. Subsequently, methods of the study had been modified to produce more reliable estimates of national statistics on utilisation of medicines.

The aim of medicines utilisation study

Medicines utilisation study was conducted with the aim to produce high quality, trusted and timely information on utilisation of medicines for the use in decision making pertaining to pharmaceutical products and pharmacotherapy. Hence, the main objective of the study is to quantify current state of medicines utilised by various sectors and levels in the nation healthcare system.

The findings of medicines utilisation study are valuable in numerous aspects of healthcare services. These include:

i. Estimating medicines consumption and depicting extensiveness and the pattern of medicines utilisation for various therapeutic groups, ii. Quantifying the number of medicine users which provide clue to the exposure rate of population to medicines of interest, iii. Assessing the extent of disease treatment in relation to disease prevalence. Comparison of the statistics to national disease prevalence could produce information on the extensiveness of disease treatment, iv. Evaluating the outcome of interventions or implementation of new policy related to pharmaceutical services by studying the impact on trend of medicines utilisation, v. In the field of pharmacovigilance, rate of adverse drug reactions and risk of exposure could be estimated by examining the link between medicine utilisation and number of adverse events observed, vi. As a guide in estimating expenditure of medicines to support medicines budget planning.

Quantifying medicines utilisation: anatomical therapeutic chemical (ATC) classification system and defined daily dose (DDD) as unit of measurement

Methodology on medicines utilisation study recommended by World Health Organisation (WHO) was referred in conducting this study.1,2 This methodology recommends the use of anatomical therapeutic chemical (ATC) classification system as a standard in grouping and coding of medicines and defined

daily dose (DDD) in quantifying medicines utilisation. Hence, ATC classification system and DDD is the measuring standard and unit in presenting medicines utilisation. The uniformity in reporting of medicines utilisation by using ATC/DDD system permits comparison of statistics at regional and international levels, between countries, populations, various levels of services and at specific time frame.

By applying ATC classification system, each medicine of known chemical substances, either single or in combination, is assigned a code which is classified in a hierarchy. This hierarchy consists of five levels. Every level represents specific information related to medicines and codes are assigned accordingly. Code assigned at Level 1 is an alphabet that represents the anatomical main group and there are 14 groups in total.

Level 1 Anatomical main group A Alimentary tract and metabolism B Blood and blood forming organs C Cardiovascular system D Dermatologicals G Genito urinary system and sex hormones H Systemic hormonal preparations, excluding sex hormones and insulins J Antiinfective for systemic use L Antineoplastic and immunomodulating agents M Musculo-skeletal system N Nervous system P Antiparasitic products, insecticides and repellents R Respiratory system S Sensory system V Various

At Level 2 to 5, the code is a combination of alphabet and number. Level 2 of ATC code refers to therapeutic subgroup. The code is further divided into pharmacological and chemical subgroup at Level 3 and 4, respectively. Lastly, code at Level 5 is assigned according to chemical substances. The structure of the code as shown below is the complete classification system by taking simvastatin as an example.

Level Group/Subgroup ATC code for simvastatin and details Level 1 Anatomical main group C Cardiovascular system Level 2 Therapeutic subgroup C10 Lipid modifying agents Level 3 Pharmacological subgroup C10A Lipid modifying agents, plain Level 4 Chemical subgroup C10A A HMG CoA reductase inhibitors Level 5 Chemical substance C10A A01 simvastatin

Interpretation of defined daily dose (DDD), DDDs per-1,000 inhabitants per-day and DDDs per-inhabitants per-year

DDD is the assumed average maintenance dose per-day for a drug used for its main indication in adults. It is a technical measure of medicines utilisation and does not necessarily agree with the recommended or prescribed daily dose. Doses for individual patients and patient groups will often vary from DDD. DDD is often a compromise dose based on review of the available information about doses used in various countries. It may even be a dose rarely prescribed because it is an average of two or more commonly used doses.

Statistics on medicines reported in MSOM for most drugs are presented as numbers of DDDs per-1,000 inhabitants per-day. DDDs per-1,000 inhabitants per-day is a crude estimate of the proportion of population treated daily with the drug. For instance, 10 DDDs per-1,000 inhabitants per-day would represent 10 in 1,000 or 1% of the population, on average, were prescribed or administered a certain drug or group of drugs every day in the year of study.

DDDs per-1,000 inhabitants per-day is useful for drugs used in the treatment of chronic diseases and when agreement between average prescribed daily dose and DDD is satisfactory. For most drugs, number of DDDs per-1,000 inhabitants per-day reported are determined for the entire population. Therefore, all age groups and gender are included in calculation. In circumstances when drug use is limited to certain age groups or gender, it would be more appropriate expressing the figure for the relevant age groups or gender only, such as, DDDs per-1,000 children age below 12 years old per-day, or DDDs per-1,000 women in reproductive age groups per-day.

For drugs administered for short duration, such as antiinfectives and antihistamines, utilisations are expressed as DDD per-inhabitant per-year. This estimate is interpreted as average number of days for one case been treated annually. Thus, 5 DDDs per-inhabitant per-year indicates that the utilisation is equivalent to the treatment of every inhabitant with a 5-day course in respective years.

There are several limitations to be considered when interpreting the statistics on medicine utilisation. These include:

i. DDD is based on one main indication of a medicine in adults, though the medicine may have several indications. ii. Medicines procured, as was the type of data collected in this study, may not all be consumed. iii. For certain medicines, DDD may be difficult to be determined or are not assigned at all, for instance, medicines with multiple ingredients, topical products, antineoplastics, anaesthetic agents and contrast media. iv. The DDD assigned to a drug is primarily based on other countries’ experience and may not reflect the average prescribed adult dose in Malaysia. v. Medicines newly introduced into the market may not have ATC code and DDD assigned yet.

For most parts of this report, only drugs with WHO-assigned DDDs are included in the utilisation statistics. However, a few groups of drugs which do not have WHO-assigned DDDs, namely the antineoplastics, dermatologicals, ophthalmologicals, otologicals, cough and cold combinations and vaccines, DDDs were assigned based on the WHO general guidelines.2 Thus, the national utilisation and patterns of use are presented in relative to drugs within the respective groups only.

THE METHODS

For MSOM, methodology of medicines utilisation study recommended by WHO was applied.1,2 These methods include identifying data to be collected and used, data analysis and in interpreting statistics on medicines.

Scope of the study

All pharmaceutical products classified as poison by legislative authority in Malaysia and listed in Poison Act 1952 (revised 1989) were included in report.3 Other medicines included are several over-the-counter (OTC) medicines. These include paracetamol, acetylsalicylic acid, vitamin and mineral supplements which contain single ingredient. Medicines and other pharmaceutical products excluded from analysis in medicines utilisation were medicated dressings, disinfectant products and medicines with no DDD assigned or no unit of measurement. This category of medicines were anaesthetics, antidotes, dialysate, parenteral nutritional products, contrast media and radiopharmaceutical products. Nevertheless, in determining expenditure on medicines, all pharmaceutical products assigned with ATC code were included, although utilisation were not reported.

Source of data

Data of year 2015 and 2016 were obtained from several sources. For public sector, contributors of data were MoH and Ministry of Education Malaysia (MoE). There were three sources of data through which MoH data were obtained, depending on the mode of procurement. First data source was long-term contract supplier of pharmaceutical products which supplied medicines to all MoH health facilities. Second source of data were short-term contract suppliers. Procurement data of other pharmaceutical products not acquired from first and second sources were collected from all MoH health facilities that had procured medicines in small quantities. Facilities included were hospitals, divisional health departments or offices and health institutes. Three public university hospitals in MoE were involved in data collection, namely Universiti Malaya Medical Centre, Universiti Sains Malaysia Hospital and Universiti Kebangsaan Malaysia Medical Centre.

Private sector medicines sales data were acquired through IQVIA Solution Malaysia Sdn Bhd, a Human Data Science company in Malaysia. IQVIA captures sales data of medicines and health products from various sources. The bulk of medicine sales transacted by pharmaceutical companies in Malaysia were obtained through main pharmaceutical distributors in Malaysia. At the time of study, this represents approximately 63% of the pharmaceutical market coverage in Malaysia. In addition, some medicine sales data are also collected from all direct transactions made by pharmaceutical manufacturers which are predominantly local manufacturers, and also from other distributors and healthcare institutions. This

contributed an additional 8% to the total pharmaceutical market coverage. For the next 11% of the pharmaceutical market coverage, medicines sales data were estimated through sampling from panels of selected retailers which include sales transacted by general practitioners, pharmacies and private hospitals. To complete the pharmaceutical market coverage, the remaining 18% were estimated from medicine sales made to other retailers that include supermarkets, shops and convenient stores.

Data configuration and analysis

Data sets of year 2015 and 2016 for public and private sectors were acquired in October 2019 and consolidated for analysis. Each pharmaceutical product with respect to the chemical substances and route of administration, was assigned with ATC code, DDD and the unit of DDD.2 Quality checking on accuracy and consistency of data coding and structuring were implemented. Subsequently, pharmaceutical products to be included in the report of MSOM 2015-2016 were selected in prior to data analysis.

Firstly, in the determination of medicines utilisation for each ATC code, estimated total dose of drug or chemical substances contain in pharmaceutical products was calculated. This was followed by determination of number of DDDs, with respect to the ATC code and year of study using following equations:

^ T DDDs per-1,000 inhabitants per-day = x 1,000 DDD x P x d

^ T DDDs per-inhabitant per-year = DDD x P

^ T An estimate of the total dose of drug or chemical substance, by ATC code and year of study DDD Defined daily dose assigned to medicine according to WHO ATC/DDD system P Mid-year population d Total number of days in year of study

Mid-year population used in above equations were 31,186,100 and 31,633,500, respectively, for year 2015 and 2016.4 Consequently, total number of DDDs for all medicines and pharmaceutical products assigned with the same ATC code for each year of study and respectively for public and private sectors were obtained and presented in this report. Likewise, total expenditure on medicines was calculated by summation of total expenditure for all pharmaceutical products assigned with the same ATC code, by year and by sector.

REFERENCES

1. Methods to Analyse Medicine Utilization and Expenditure to Support Pharmaceutical Policy Implementation; World Health Organization: Geneva, 2018. Licence: CC BY-NC-SA 3.0 IGO. 2. Guidelines for ATC Classification and DDD Assignment 2018; WHO Collaborating Centre for Drug Statistics Methodology: Oslo, Norway, 2017. 3. Poison Act 1952 (revised 1989), Act 336 Laws of Malaysia; International Law Book Services: Kuala Lumpur, 1989. 4. Department of Statistics Malaysia. http://www.dosm.gov.my (accessed July 3, 2019).

Utilisation of Medicines in Malaysia Azzy Iyzati Ahmad Shanizza, Rosliana Rosli, Yusmiza Azmi, Sarahfarina Abdul Rahim, Rozita Mohamad, Mary Chok Chiew Fong 2

Accurate national medicines utilisation statistics is crucial for healthcare policy-makers to make informed decisions in developing policies towards promoting rational use of medicines in the country. The information is also essential to monitor the impact of any educational, regulatory or policy interventions being made in our continuous efforts to improve the current drug use practices.

In this chapter, the national estimates of total medicines utilisation in Malaysia for both 2015 and 2016 are reported in several tables in order of utilisation by therapeutic groups and individual drugs or chemical substances. Medicines utilisation in the public and private sectors are also tabulated and discussed accordingly.

Overall, the total estimated medicines utilisation in 2015 and 2016 were reported at 624.90 and 632.32 DDD/1,000 inhabitants/day, respectively (Table 2.1). In 2015, the total medicines utilisation estimated for the public sector was 398.41 DDD/1,000 inhabitants/day, which accounted for 63.8%. Whereas the private sector reported a total of 226.49 DDD/1,000 inhabitants/day at 36.2%. The total medicines utilisation estimated for the public sector in 2016 was 407.82 DDD/1,000 inhabitants/day (64.5%) while the private sector observed a slight drop at 224.5 DDD/1,000 inhabitants/day (35.5%). Year to year comparison observed an upward trend of total medicines utilisation with a 9.7% increase from 569.55 DDD/1,000 inhabitants/day in 20141 and a modest increase of 1.2% between 2015 and 2016. The overall increase in drug utilisation from 2015 to 2016 was mainly contributed by the public sector that had increased by 2.4% while the private sector reported a negligible decrease of 0.9%.

Table 2.1 Total estimation of medicine utilisation, 2015-2016 (Utilisation in DDD/1,000 inhabitants/day) Sector 2015 2016 Public 398.41 (63.8%) 407.82 (64.5%) Private 226.49 (36.2%) 224.50 (35.5%) Total 624.90 632.32

Total medicines utilisation for the top 50 therapeutic groups in 2016 and 2015 are presented in Table 2.2 and 2.3, respectively. Overall, there were no marked differences in therapeutic groups between the two years, in particular the top 10 therapeutic groups. Drugs used in diabetes (A10) remained the most utilised therapeutic group for 2015 and 2016. This was followed by calcium channel blockers (C08), agents acting on the renin-angiotensin system (C09) and lipid modifying agents (C10), which were also ranked the same for both years. The estimated total utilisation of these groups of drugs is consistent with the reported diseases prevalence in National Health and Morbidity Survey (NHMS) 2015 for non-communicable diseases (NCD), particularly cardiovascular diseases (CVD) which contributed to an estimate of 73% of total deaths in Malaysia.2 The only new therapeutic group that climbed into the top 10 ranking in 2016 was sex hormones and modulators of the genital system (G03), pushing down the drugs for obstructive airway diseases (R03) to the twelfth position.

Table 2.4 shows that the most significant increase in utilisation (20.0%) between 2015 and 2016 was seen for agents acting on the renin-angiotensin system (C09) from 42.2187 to 50.6757 DDD/1,000 inhabitants/ day, followed by sex hormones and modulators of the genital system (G03) with an increase of 16.4% from 14.6267 in 2015 to 17.0276 DDD/1,000 inhabitants/day in 2016. On the other hand, utilisation for beta blocking agents (C07) decreased by 11.6% from 20.0549 to 17.7193 DDD/1,000 inhabitants/day and diuretics (C03) also reported a reduction in utilisation by 9.1% from 18.5823 to 16.8841 DDD/1,000 inhabitants/day.

Table 2.2 Top 50 utilised therapeutic groups in 2016 (Utilisation in DDD/1,000 inhabitants/day) Rank ATC code Therapeutic group Public Private Total 1 A10 Drugs used in diabetes 61.9611 11.3131 73.2742 2 C08 Calcium channel blockers 61.5062 7.5324 69.0386 3 C09 Agents acting on the renin-angiotensin system 39.3969 11.2788 50.6757 4 C10 Lipid modifying agents 27.6987 8.9001 36.5988 5 A11 Vitamins 4.7050 18.1011 22.8061 6 R06 Antihistamines for systemic use 4.7791 17.2892 22.0683 7 C07 Beta blocking agents 14.2129 3.5064 17.7193 8 G03 Sex hormones and modulators of the genital system 8.3373 8.6904 17.0276 9 C03 Diuretics 14.9246 1.9595 16.8841 10 B03 Antianemic preparations 12.5961 3.4350 16.0311 11 B01 Antithrombotic agents 10.5104 4.3203 14.8307 12 R03 Drugs for obstructive airway diseases 8.5853 5.3016 13.8869 13 M01 Antiinflammatory and antirheumatic products 2.0019 9.6440 11.6460 14 D07 Corticosteroids, dermatological preparations 2.5007 8.5708 11.0715 15 A02 Drugs for acid related disorders 6.9301 3.6746 10.6047 16 J01 Antibacterials for systemic use 3.0980 7.1376 10.2356 17 D01 Antifungals for dermatological use 1.1965 7.7822 8.9787 18 N02 Analgesics 3.6324 5.3432 8.9757 19 R05 Cough and cold preparations 0.8765 6.7969 7.6734 20 S01 Ophthalmologicals 3.5475 2.9027 6.4502 21 H02 Corticosteroids for systemic use 2.3627 3.8385 6.2012 22 C01 Cardiac therapy 3.4076 1.3260 4.7337 23 R01 Nasal preparations 0.7375 3.9016 4.6391 24 N05 Psycholeptics 2.7182 1.2788 3.9970 25 A12 Mineral supplements 3.1342 0.4378 3.5721 26 D11 Other dermatological preparations 0.0383 3.4883 3.5266 27 D06 Antibiotics and chemotherapeutics for 1.1633 1.6163 2.7796 dermatological use 28 H03 Thyroid therapy 1.6079 1.0488 2.6567 29 A06 Drugs for constipation 1.0752 1.5805 2.6556 30 C02 Antihypertensives 2.3668 0.2655 2.6323 31 G04 Urologicals 1.6394 0.9789 2.6182 32 D05 Antipsoriatics 0.3115 2.1572 2.4687 33 N07 Other nervous system drugs 1.3078 1.1206 2.4284 34 N06 Psychoanaleptics 1.3971 0.9546 2.3517 35 A03 Drugs for functional gastrointestinal disorders 0.4834 1.7039 2.1873 36 N03 Antiepileptics 1.6813 0.3884 2.0697 37 D10 Anti-acne preparations 0.0848 1.8418 1.9266 38 M04 Antigout preparations 0.9175 0.9125 1.8300 39 J05 Antivirals for systemic use 1.2096 0.2021 1.4117 40 M03 Muscle relaxants 0.1293 0.9284 1.0578 41 A07 Antidiarrheals, intestinal antiinflammatory/ 0.2799 0.6942 0.9741 antiinfective agents 42 S03 Ophthalmological and otological preparations 0.0489 0.8160 0.8649 43 N04 Anti-parkinson drugs 0.6800 0.1455 0.8255 44 M05 Drugs for treatment of bone diseases 0.2341 0.4773 0.7114 45 L04 Immunosuppressants 0.4721 0.1740 0.6460 46 J04 Antimycobacterials 0.5427 0.0881 0.6308 47 L02 Endocrine therapy 0.3582 0.2282 0.5864 48 A08 Antiobesity preparations, excluding diet products 0.0008 0.4575 0.4583 49 G01 Gynecological antiinfectives and antiseptics 0.0518 0.3163 0.3681 50 P01 Antiprotozoals 0.1607 0.1377 0.2985

Table 2.3 Top 50 utilised therapeutic groups in 2015 (Utilisation in DDD/1,000 inhabitants/day) Rank ATC code Therapeutic group Public Private Total

1 A10 Drugs used in diabetes 63.7128 11.3484 75.0611 2 C08 Calcium channel blockers 59.8844 7.8863 67.7707 3 C09 Agents acting on the renin-angiotensin system 31.3996 10.8191 42.2187 4 C10 Lipid modifying agents 26.6695 8.7064 35.3759 5 A11 Vitamins 5.4220 18.0759 23.4979 6 R06 Antihistamines for systemic use 5.6576 17.0806 22.7382 7 C07 Beta blocking agents 16.3077 3.7472 20.0549 8 C03 Diuretics 16.5607 2.0216 18.5823 9 B03 Antianemic preparations 13.7792 3.2419 17.0211 10 R03 Drugs for obstructive airway diseases 9.2977 5.5902 14.8878 11 G03 Sex hormones and modulators of the genital 5.1826 9.4441 14.6267 system 12 B01 Antithrombotic agents 10.1636 4.1843 14.3480 13 M01 Antiinflammatory and antirheumatic products 2.3547 11.2517 13.6065 14 D07 Corticosteroids, dermatological preparations 2.8156 8.5429 11.3586 15 A02 Drugs for acid related disorders 7.2656 3.7382 11.0038 16 J01 Antibacterials for systemic use 3.3678 7.5133 10.8810 17 D01 Antifungals for dermatological use 1.3972 8.4211 9.8183 18 N02 Analgesics 4.1205 5.5553 9.6759 19 R05 Cough and cold preparations 0.9183 6.8790 7.7973 20 H02 Corticosteroids for systemic use 2.5610 3.9168 6.4778 21 S01 Ophthalmologicals 3.2125 2.6949 5.9074 22 R01 Nasal preparations 0.9372 3.9439 4.8811 23 C01 Cardiac therapy 3.4602 1.2999 4.7601 24 N05 Psycholeptics 2.8144 1.4146 4.2290 25 A12 Mineral supplements 3.4623 0.5894 4.0517 26 D11 Other dermatological preparations 0.0302 3.4062 3.4364 27 D06 Antibiotics and chemotherapeutics for 1.2411 1.5938 2.8349 dermatological use 28 A03 Drugs for functional gastrointestinal disorders 0.7283 2.0165 2.7448 29 H03 Thyroid therapy 1.7186 1.0058 2.7244 30 D05 Antipsoriatics 0.5463 2.0592 2.6056 31 C02 Antihypertensives 2.3031 0.2651 2.5683 32 G04 Urologicals 1.6195 0.9278 2.5474 33 N06 Psychoanaleptics 1.4205 1.0645 2.4850 34 A06 Drugs for constipation 0.7783 1.5965 2.3748 35 N07 Other nervous system drugs 1.1979 1.1139 2.3118 36 N03 Antiepileptics 1.8070 0.3652 2.1723 37 D10 Anti-acne preparations 0.1252 1.7448 1.8700 38 M04 Antigout preparations 0.9282 0.9346 1.8628 39 M03 Muscle relaxants 0.1673 1.0697 1.2370 40 J05 Antivirals for systemic use 0.9871 0.2463 1.2334 41 A07 Antidiarrheals, intestinal antiinflammatory/ 0.2890 0.6690 0.9580 antiinfective agents 42 S03 Ophthalmological and otological preparations 0.0565 0.9012 0.9578 43 N04 Anti-parkinson drugs 0.7606 0.1318 0.8925 44 M05 Drugs for treatment of bone diseases 0.2941 0.5452 0.8393 45 J04 Antimycobacterials 0.6305 0.0764 0.7070 46 L02 Endocrine therapy 0.3567 0.2012 0.5579 47 A08 Antiobesity preparations, excluding diet products 0.0028 0.5394 0.5422 48 L04 Immunosuppressants 0.3728 0.1602 0.5330 49 P01 Antiprotozoals 0.1940 0.1601 0.3541 50 G01 Gynecological antiinfectives and antiseptics 0.0584 0.2920 0.3504

Table 2.4 Top 10 utilised therapeutic groups in public and private sector in 2016 compared to 2015 (Utilisation in DDD/1,000 inhabitants/day) Sector ATC Therapeutic group 2015 2016 Changes code Utilisation Rank Utilisation Rank from 2015 (%)

Public A10 Drugs used in diabetes 75.0611 1 73.2742 1 -2.4 and C08 Calcium channel blockers 67.7707 2 69.0386 2 1.9 private C09 Agents acting on the renin- 42.2187 3 50.6757 3 20.0 angiotensin system C10 Lipid modifying agents 35.3759 4 36.5988 4 3.5 A11 Vitamins 23.4979 5 22.8061 5 -2.9 R06 Antihistamines for systemic use 22.7382 6 22.0683 6 -2.9 C07 Beta blocking agents 20.0549 7 17.7193 7 -11.6 G03 Sex hormones and modulators of 14.6267 11 17.0276 8 16.4 the genital system C03 Diuretics 18.5823 8 16.8841 9 -9.1 B03 Antianemic preparations 17.0211 9 16.0311 10 -5.8 Public A10 Drugs used in diabetes 63.7128 1 61.9611 1 -2.7 C08 Calcium channel blockers 59.8844 2 61.5062 2 2.7 C09 Agents acting on the renin- 31.3996 3 39.3969 3 25.5 angiotensin system C10 Lipid modifying agents 26.6695 4 27.6987 4 3.9 C03 Diuretics 16.5607 5 14.9246 5 -9.9 C07 Beta blocking agents 16.3077 6 14.2129 6 -12.8 B03 Antianemic preparations 13.7792 7 12.5961 7 -8.6 B01 Antithrombotic agents 10.1636 8 10.5104 8 3.4 R03 Drugs for obstructive airway 9.2977 9 8.5853 9 -7.7 diseases G03 Sex hormones and modulators of 5.1826 13 8.3373 10 60.9 the genital system Private A11 Vitamins 18.0759 1 18.1011 1 0.1 R06 Antihistamines for systemic use 17.0806 2 17.2892 2 1.2 A10 Drugs used in diabetes 11.3484 3 11.3131 3 -0.3 C09 Agents acting on the renin- 10.8191 5 11.2788 4 4.2 angiotensin system M01 Antiinflammatory and 11.2517 4 9.6440 5 -14.3 antirheumatic products C10 Lipid modifying agents 8.7064 7 8.9001 6 2.2 G03 Sex hormones and modulators of 9.4441 6 8.6904 7 -8.0 the genital system D07 Corticosteroids, dermatological 8.5429 8 8.5708 8 0.3 preparations D01 Antifungals for dermatological use 8.4211 9 7.7822 9 -7.6 C08 Calcium channel blockers 7.8863 10 7.5324 10 -4.5

Public and private sector comparison of medicine utilisation by therapeutic groups are presented in Table 2.4. The overall increase in utilisation of sex hormones and modulators of the genital system (G03) was mainly contributed by the public sector of which the utilisation of this therapeutic group increased by a total of 60.9% from 5.1826 to 8.3373 DDD/1,000 inhabitants/day, particularly the hormonal contraceptives for systemic use (G03A). This increasing trend may be contributed by the initiatives carried out by the public primary health clinics to promote awareness in family planning as explained in chapter 8.

Utilisation of vitamins (A11) topped the list in the private sector for both 2015 and 2016 at 18.0759 and 18.1011 DDD/1,000 inhabitants/day, respectively. The use on non-prescription drugs, vitamins (A11), antihistamines for systemic use (R06), and corticosteroid, dermatological preparations (D07) continued to be reported higher in the private sector. Similar trend was reported in MSOM 2011-2014 whereby patients with mild and acute conditions prefer to seek treatment at private healthcare sector, while most patients with chronic conditions and NCDs such as diabetes mellitus, hypertension, and dyslipidaemia were being treated in the public sector.1

Table 2.5 Top 50 utilised drugs/chemical substances in 2016 (Utilisation in DDD/1,000 inhabitants/day) Rank ATC code Drug/Chemical substance Public Private Total

1 C08C A01 Amlodipine 56.8378 6.5670 63.4048 2 A10B B09 Gliclazide 31.4109 3.8507 35.2616 3 C09A A04 Perindopril 28.4049 1.5762 29.9811 4 C10A A01 Simvastatin 20.0099 2.2834 22.2933 5 A10B A02 Metformin 15.4539 2.3545 17.8084 6 B01A C06 Acetylsalicylic acid 8.5408 2.2761 10.8170 7 C03A A03 Hydrochlorothiazide 9.7083 0.6339 10.3421 8 C10A A05 Atorvastatin 6.2988 3.3942 9.6930 9 B03B B01 Folic acid 8.1811 1.4638 9.6448 10 N02B E01 Paracetamol 3.2542 4.8738 8.1280 11 R06A E07 Cetirizine 0.2769 7.7533 8.0302 12 C07A B03 Atenolol 5.7586 1.8108 7.5694 13 C07A B02 Metoprolol 6.6570 0.2888 6.9458 14 R03A C02 Salbutamol 3.0570 2.4187 5.4757 15 C03C A01 Furosemide 4.3935 0.5820 4.9755 16 C09A A02 Enalapril 4.3446 0.5258 4.8705 17 A10A D01 Insulin (human), intermediate- or long-acting 4.7343 0.0292 4.7635 combined with fast-acting 18 R06A X13 Loratadine 1.9044 2.7172 4.6216 19 R06A B04 Chlorphenamine 1.8143 2.3670 4.1812 20 H02A B06 Prednisolone 1.5117 2.5315 4.0432 21 D01A C20 Imidazoles/triazoles in combination with 0.0052 3.8180 3.8232 corticosteroids 22 C08C A02 Felodipine 3.4149 0.2913 3.7063 23 A02B A02 Ranitidine 3.3000 0.3206 3.6206 24 G03A C06 Medroxyprogesterone 2.9583 0.5052 3.4635 25 R05C A10 Expectorants, combinations 0.0056 3.3696 3.3753 26 G03A A07 Levonorgestrel and ethinylestradiol 1.6194 1.5612 3.1806 27 B03A A02 Ferrous fumarate 3.1094 0.0603 3.1698 28 A10B D02 Metformin and sulfonylureas 2.3387 0.8232 3.1619 29 A02B C01 Omeprazole 2.2826 0.8608 3.1434 30 G03A A09 Desogestrel and ethinylestradiol 1.2644 1.8766 3.1410 31 A10A B01 Insulin (human), fast-acting 3.0928 0.0083 3.1011 32 D11A C03 Selenium compounds 0.0067 3.0611 3.0678 33 M01A B05 Diclofenac 0.7215 2.2701 2.9916 34 D07A C01 Betamethasone 1.3932 1.4182 2.8114 35 C09C A01 Losartan 1.6740 1.1167 2.7907 36 J01C A04 Amoxicillin 1.1055 1.6164 2.7219 37 A10A C01 Insulin (human), intermediate-acting 2.5525 0.0050 2.5574 38 R03B A02 Budesonide 2.4663 0.0658 2.5321 39 C01E B15 Trimetazidine 1.6997 0.7260 2.4256 40 G03A C01 Norethisterone 1.6351 0.6342 2.2693 41 D07A D01 Clobetasol 0.0312 2.1441 2.1752 42 B01A C04 Clopidogrel 0.6873 1.4428 2.1301 43 C10A A07 Rosuvastatin 0.1318 1.9697 2.1015 44 C07A B07 Bisoprolol 1.3677 0.7246 2.0923 45 M01A G01 Mefenamic acid 0.5302 1.5307 2.0609 46 C09C A07 Telmisartan 1.0932 0.9527 2.0458 47 D07C C01 Betamethasone and antibiotics 0.0282 2.0113 2.0394 48 D07A A02 Hydrocortisone 0.9086 1.0742 1.9828 49 A02B C02 Pantoprazole 0.9729 0.8655 1.8384 50 A10B B01 Glibenclamide 1.1987 0.5966 1.7953

Table 2.6 Top 50 utilised drugs/chemical substances in 2015 (Utilisation in DDD/1,000 inhabitants/day) Rank ATC code Drug/Chemical substance Public Private Total

1 C08C A01 Amlodipine 54.6063 6.9215 61.5278 2 A10B B09 Gliclazide 34.6899 3.5650 38.2548 3 C10A A01 Simvastatin 21.4087 2.4403 23.8490 4 C09A A04 Perindopril 21.7401 1.4823 23.2224 5 A10B A02 Metformin 16.6506 3.0228 19.6733 6 B03B B01 Folic acid 9.8231 1.6219 11.4450 7 C03A A03 Hydrochlorothiazide 10.5393 0.6105 11.1499 8 B01A C06 Acetylsalicylic acid 8.2776 2.3874 10.6650 9 C07A B03 Atenolol 6.8768 2.0422 8.9190 10 N02B E01 Paracetamol 3.8194 4.8978 8.7173 11 C07A B02 Metoprolol 8.1411 0.2942 8.4353 12 R06A E07 Cetirizine 0.4506 7.3811 7.8318 13 C10A A05 Atorvastatin 3.6784 3.2641 6.9425 14 R03A C02 Salbutamol 3.4186 2.6627 6.0813 15 C03C A01 Furosemide 5.0400 0.4685 5.5085 16 R06A B04 Chlorphenamine 2.0985 2.7515 4.8500 17 R06A X13 Loratadine 2.1142 2.4021 4.5164 18 M01A B05 Diclofenac 1.0173 3.3311 4.3484 19 H02A B06 Prednisolone 1.5955 2.6309 4.2264 20 A02B A02 Ranitidine 3.7358 0.4796 4.2154 21 C09A A02 Enalapril 3.5275 0.5672 4.0947 22 D01A C20 Imidazoles/triazoles in combination with 0.0016 3.9594 3.9610 corticosteroids 23 B03A A02 Ferrous fumarate 3.4457 0.0575 3.5033 24 C08C A02 Felodipine 3.1879 0.2795 3.4674 25 A02B C01 Omeprazole 2.4556 0.8574 3.3130 26 R05C A10 Expectorants, combinations - 3.2711 3.2711 27 A10A D01 Insulin (human), intermediate- or long-acting 3.0917 0.0308 3.1224 combined with fast-acting 28 D11A C03 Selenium compounds 0.0161 2.9619 2.9780 29 D07A C01 Betamethasone 1.3828 1.5445 2.9273 30 A10B D02 Metformin and sulfonylureas 2.0222 0.8437 2.8659 31 J01C A04 Amoxicillin 1.1254 1.6975 2.8229 32 A10B B01 Glibenclamide 2.0028 0.7251 2.7279 33 R03B A02 Budesonide 2.5870 0.0774 2.6644 34 G03A A09 Desogestrel and ethinylestradiol 0.7741 1.7994 2.5735 35 M01A G01 Mefenamic acid 0.6041 1.8817 2.4857 36 G03A A07 Levonorgestrel and ethinylestradiol 0.6550 1.7566 2.4116 37 C08C A05 Nifedipine 1.8276 0.4442 2.2719 38 D07A D01 Clobetasol 0.0860 2.1663 2.2523 39 C09C A07 Telmisartan 1.3104 0.8953 2.2057 40 D07A A02 Hydrocortisone 1.1128 1.0917 2.2045 41 G03A C06 Medroxyprogesterone 1.6554 0.5223 2.1777 42 C01E B15 Trimetazidine 1.4232 0.7033 2.1264 43 D07C C01 Betamethasone and antibiotics 0.0838 1.9918 2.0756 44 C09C A01 Losartan 0.9182 1.1337 2.0518 45 A10A C01 Insulin (human), intermediate-acting 2.0417 0.0055 2.0473 46 A10A B01 Insulin (human), fast-acting 1.9873 0.0082 1.9955 47 B01A C04 Clopidogrel 0.6856 1.2635 1.9491 48 C02C A01 Prazosin 1.8814 0.0335 1.9149 49 C10A A07 Rosuvastatin 0.1129 1.7839 1.8968 50 G03A C01 Norethisterone 1.0971 0.7864 1.8835

The top 50 utilisation by medicinal substances in 2016 and 2015 were presented in Table 2.5 and 2.6, respectively. Amlodipine (C08C A01) which is mainly used for treating hypertension remained the most utilised drug for both 2015 and 2016, respectively at 61.5278 and 63.4048 DDD/1,000 inhabitants/day. The high usage of amlodipine was in accordance with the prevalence of hypertension in Malaysia as reported in the NHMS and its wider accessibility due to prescriber category. Amlodipine is listed in Category B in the Ministry of Health Medicines Formulary (MoHMF), in which the group of prescribers is extended to medical officers at MoH.2,3 Table 2.7 shows that drugs for diabetes namely gliclazide (A10B B09) and metformin (A10B A02) remained in the top 10 ranking for both years despite the slight decrease in utilisation by 7.8% and 9.5%, respectively. The antihypertensive drug, perindopril (C09A A04) and drug for hypercholesterolemia, simvastatin (C10A A01) also remained within the top 10 drugs from 2015 to 2016.

Table 2.7 Top 10 utilised drugs/chemical substances in public and private sector in 2016 compared to 2015 (Utilisation in DDD/1,000 inhabitants/day) Sector ATC code Drug/Chemical substance 2015 2016 Changes Utilisation Rank Utilisation Rank from 2015 (%)

Public C08C A01 Amlodipine 61.5278 1 63.4048 1 3.1 and A10B B09 Gliclazide 38.2548 2 35.2616 2 -7.8 private C09A A04 Perindopril 23.2224 4 29.9811 3 29.1 C10A A01 Simvastatin 23.8490 3 22.2933 4 -6.5 A10B A02 Metformin 19.6733 5 17.8084 5 -9.5 B01A C06 Acetylsalicylic acid 10.6650 8 10.8170 6 1.4 C03A A03 Hydrochlorothiazide 11.1499 7 10.3421 7 -7.2 C10A A05 Atorvastatin 6.9425 13 9.6930 8 39.6 B03B B01 Folic acid 11.4450 6 9.6448 9 -15.7 N02B E01 Paracetamol 8.7173 10 8.1280 10 -6.8 Public C08C A01 Amlodipine 54.6063 1 56.8378 1 4.1 A10B B09 Gliclazide 34.6899 2 31.4109 2 -9.5 C09A A04 Perindopril 21.7401 3 28.4049 3 30.7 C10A A01 Simvastatin 21.4087 4 20.0099 4 -6.5 A10B A02 Metformin 16.6506 5 15.4539 5 -7.2 C03A A03 Hydrochlorothiazide 10.5393 6 9.7083 6 -7.9 B01A C06 Acetylsalicylic acid 8.2776 8 8.5408 7 3.2 B03B B01 Folic acid 9.8231 7 8.1811 8 -16.7 C07A B02 Metoprolol 8.1411 9 6.6570 9 -18.2 C10A A05 Atorvastatin 3.6784 14 6.2988 10 71.2 Private R06A E07 Cetirizine 7.3811 1 7.7533 1 5.0 C08C A01 Amlodipine 6.9215 2 6.5670 2 -5.1 N02B E01 Paracetamol 4.8978 3 4.8738 3 -0.5 A10B B09 Gliclazide 3.5650 5 3.8507 4 8.0 D01A C20 Imidazoles/triazoles in 3.9594 4 3.8180 5 -3.6 combination with corticosteroids C10A A05 Atorvastatin 3.2641 8 3.3942 6 4.0 R05C A10 Expectorants, combinations 3.2711 7 3.3696 7 3.0 D11A C03 Selenium compounds 2.9619 10 3.0611 8 3.3 R06A X13 Loratadine 2.4021 15 2.7172 9 13.1 H02A B06 Prednisolone 2.6309 13 2.5315 10 -3.8

Amlodipine was ranked first as the highly utilised drug in the public sector from 2015 to 2016, and came second in the private sector, after cetirizine (R06A E07). Atorvastatin (C10A A05) was reported to have the highest increase in utilisation within the public sector from 2015 to 2016 by 71.2% from 3.6784 to 6.2988 DDD/1,000 inhabitants/day, followed by perindopril with an increase of 30.7% from 21.7401 DDD/1,000 inhabitants/day in 2015 to 28.4049 DDD/1,000 inhabitants/day in 2016. Metoprolol (C07A B02) however, was reported to decline in utilisation by 18.2% from 8.1411 to 6.6570 DDD/1,000 inhabitants/day. Interestingly, beta blocking agent, atenolol (C07A B03) rightly moved out of the top 10 ranking in 2016 indicating the shift of prescribing pattern towards lower use of these agents. The reduction in use of metoprolol and atenolol was possibly due to the change of prescriber category for a newer agent such as bisoprolol (C07A B07) in the public practice, promoting its increase in utilisation and moved up into the top 50 utilisation list in 2016 (Table 2.5). The drastic leap in ranking worth noting was the utilisation of insulins, primarily combinations of intermediated- or long-acting and fast-acting insulins (A10A D01), fast-acting

insulins (A10A B01), and intermediate-acting insulins (A10A C01). Overall usage of these insulins had increased by 52. 6%, 55.4% and 24.9%, respectively. The increasing trend of insulin utilisation may be linked to the changes in usage of other antidiabetic drugs as discussed in Chapter 4.

In conclusion, overall national medicines utilisation continued to show an upward trend albeit a modest increase of 1.2% between 2015 and 2016. No major changes were observed in the ranking of both the therapeutic groups and drugs or chemical substances. This is in parallel with the prevalence of chronic diseases reported in the NHMS 2015.2

REFERENCES

1. Malaysian Statistics on Medicines 2011-2014; Pharmaceutical Services Division, Ministry of Health Malaysia: Kuala Lumpur, 2017. 2. Volume II: Non-Communicable Disease, Risk Factors and Other Health Problems. National Health and Morbidity Survey 2015; National Institutes of Health, Ministry of Health Malaysia: Kuala Lumpur, 2015. 3. Pharmaceutical Services Programme, Ministry of Health Malaysia. https://www.pharmacy.gov.my (accessed February 3, 2020), Ministry of Health Medicines Formulary.

Expenditures on Medicines in Malaysia Tineshwaran Velvanathan, Nazatul Syima Idrus, Muhammad Md Zain, Wan Utma Sapini Wan Abdul Samad, Rosliza Lajis 3 Table 3.1 Top 50 expenditure on drugs/chemical substances in 2016 (Expenditure in MYR `000) Rank ATC code Drug/Chemical substance Public Private Total 1 A10B A02 Metformin 64,163.68 24,668.15 88,831.83 2 B03X A01 Erythropoietin 20,641.92 68,041.96 88,683.88 3 A10B B09 Gliclazide 44,033.04 37,650.74 81,683.78 4 C10A A05 Atorvastatin 7,958.14 71,697.31 79,655.46 5 J07C A06 Diphtheria-Hemophilus influenzae B-pertussis- 56,002.56 10,278.64 66,281.19 poliomyelitis-tetanus 6 N02B E01 Paracetamol 20,490.62 40,394.67 60,885.30 7 J01C R02 Amoxicillin and beta-lactamase inhibitor 20,685.74 38,818.33 59,504.07 8 C10A A07 Rosuvastatin 1,757.50 54,223.53 55,981.04 9 C08C A01 Amlodipine 9,847.87 44,870.44 54,718.30 10 B01A C04 Clopidogrel 4,181.61 48,111.92 52,293.53 11 J01D C02 Cefuroxime 19,377.66 32,408.92 51,786.58 12 A02B C02 Pantoprazole 5,738.36 41,664.73 47,403.08 13 A10B D07 Metformin and sitagliptin 1,196.85 45,468.74 46,665.59 14 J01D D04 Ceftriaxone 10,068.04 35,361.48 45,429.53 15 A02B C05 Esomeprazole 7,105.84 38,258.02 45,363.86 16 C10A A01 Simvastatin 30,435.72 14,164.01 44,599.74 17 M01A H01 Celecoxib 8,710.54 33,858.55 42,569.08 18 M01A H05 Etoricoxib 1,988.51 36,067.18 38,055.69 19 C09A A04 Perindopril 24,477.76 11,878.28 36,356.05 20 A10A D01 Insulin (human), intermediate- or long-acting 34,296.71 892.61 35,189.32 combined with fast-acting 21 R01B A52 Pseudoephedrine, combinations 944.35 32,287.90 33,232.26 22 V03A C03 Deferasirox 29,733.09 594.43 30,327.51 23 A11G A01 Ascorbic acid (vitamin C) 4,057.95 25,864.84 29,922.78 24 R03A C02 Salbutamol 7,427.88 22,452.26 29,880.15 25 B05A A01 Albumin 14,413.11 14,263.16 28,676.28 26 L01X C02 Rituximab 16,082.08 12,593.65 28,675.73 27 L01X C03 Trastuzumab 12,961.00 15,498.75 28,459.75 28 L01X E01 Imatinib 24,388.03 3,789.43 28,177.46 29 C09D B01 Valsartan and amlodipine 1,305.50 26,871.19 28,176.69 30 J07A L02 Pneumococcus, purified polysaccharides 484.78 27,208.27 27,693.05 antigen conjugated 31 S01X A20 Artificial tears and other indifferent 1,781.13 24,886.44 26,667.57 preparations 32 L01X E08 Nilotinib 24,933.56 1,587.86 26,521.43 33 R06A A02 Diphenhydramine 22,836.73 3,085.09 25,921.83 34 N03A X16 Pregabalin 5,289.78 20,532.33 25,822.10 35 R03A K06 Salmeterol and fluticasone 11,376.50 13,433.87 24,810.37 36 R03D C03 Montelukast 929.30 23,659.51 24,588.82 37 C07A B07 Bisoprolol 4,645.61 18,754.33 23,399.94 38 G04B E03 Sildenafil 1,481.14 21,511.18 22,992.32 39 J01C A04 Amoxicillin 13,928.25 8,848.53 22,776.78 40 C07A B02 Metoprolol 20,819.16 1,671.73 22,490.89 41 C09C A07 Telmisartan 5,975.16 16,454.22 22,429.38 42 R05C A10 Expectorants, combinations 20.58 21,906.88 21,927.46 43 M01A H04 Parecoxib 1,527.11 20,170.47 21,697.58 44 J01C F02 Cloxacillin 19,449.98 2,135.81 21,585.79 45 A10A B01 Insulin (human), fast-acting 21,271.43 256.00 21,527.44 46 N05A H04 Quetiapine 17,037.73 4,300.68 21,338.41 47 B03A A02 Ferrous fumarate 20,888.70 97.92 20,986.62 48 J05A F10 Entecavir 4,506.22 16,185.97 20,692.19 49 B01A B01 Heparin 16,339.84 4,300.40 20,640.24 50 R06A E07 Cetirizine 135.00 20,253.53 20,388.53

Table 3.2 Top 50 expenditure on drugs/chemical substances in 2015 (Expenditure in MYR `000) Rank ATC code Drug/Chemical substance Public Private Total

1 A10B A02 Metformin 68,134.29 25,856.82 93,991.11 2 A10B B09 Gliclazide 45,314.51 35,556.98 80,871.48 3 B03X A01 Erythropoietin 13,767.44 64,804.40 78,571.84 4 C10A A05 Atorvastatin 5,275.99 67,320.12 72,596.11 5 N02B E01 Paracetamol 24,290.25 37,450.49 61,740.74 6 J07C A06 Diphtheria-Hemophilus influenzae B- 57,192.64 4,163.34 61,355.99 pertussis-poliomyelitis-tetanus 7 C10A A01 Simvastatin 45,360.16 15,367.67 60,727.83 8 C08C A01 Amlodipine 11,416.97 45,475.01 56,891.98 9 J01C R02 Amoxicillin and beta-lactamase inhibitor 20,236.08 33,996.80 54,232.88 10 B01A C04 Clopidogrel 5,673.33 48,173.01 53,846.34 11 J01D C02 Cefuroxime 19,953.67 33,574.87 53,528.54 12 C10A A07 Rosuvastatin 1,984.49 49,498.54 51,483.04 13 A02B C05 Esomeprazole 10,585.34 37,615.07 48,200.41 14 J01D D04 Ceftriaxone 10,891.56 31,778.78 42,670.34 15 A02B C02 Pantoprazole 4,362.56 37,216.47 41,579.03 16 A10B D07 Metformin and sitagliptin 1,208.89 38,869.88 40,078.77 17 M01A H01 Celecoxib 6,882.44 30,270.36 37,152.80 18 M01A H05 Etoricoxib 2,120.50 34,593.76 36,714.26 19 R01B A52 Pseudoephedrine, combinations 1,259.47 31,357.53 32,617.00 20 V03A C03 Deferasirox 31,607.54 782.75 32,390.29 21 R03A C02 Salbutamol 8,237.47 22,905.27 31,142.74 22 C09A A04 Perindopril 19,504.34 11,372.61 30,876.95 23 R06A A02 Diphenhydramine 27,021.48 3,191.33 30,212.81 24 A11G A01 Ascorbic acid (vitamin C) 4,708.28 24,552.66 29,260.94 25 S01X A20 Artificial tears and other indifferent 1,892.95 26,797.39 28,690.34 preparations 26 C09D B01 Valsartan and amlodipine 991.32 26,339.18 27,330.50 27 C07A B02 Metoprolol 25,531.78 1,677.11 27,208.89 28 G04B E03 Sildenafil 2,323.31 24,307.54 26,630.85 29 J01C A04 Amoxicillin 17,149.94 9,405.95 26,555.89 30 L01X E08 Nilotinib 24,462.46 1,721.90 26,184.35 31 C09C A07 Telmisartan 10,370.55 15,383.97 25,754.52 32 J07A L02 Pneumococcus, purified polysaccharides 314.32 25,364.77 25,679.09 antigen conjugated 33 L01X C03 Trastuzumab 10,251.59 15,291.34 25,542.93 34 R03D C03 Montelukast 1,366.21 23,621.41 24,987.62 35 B05A A01 Albumin 15,118.04 9,416.77 24,534.81 36 R03A K06 Salmeterol and fluticasone 9,770.76 14,545.39 24,316.15 37 J01C F02 Cloxacillin 22,142.01 2,071.08 24,213.09 38 L01X C02 Rituximab 12,644.57 11,472.63 24,117.20 39 J07B M01 Papillomavirus (human types 6, 11, 16, 18) 18,249.77 5,240.61 23,490.38 40 A10A D01 Insulin (human), intermediate- or long- 22,051.05 929.29 22,980.35 acting combined with fast-acting 41 B03A A02 Ferrous fumarate 22,764.62 93.84 22,858.47 42 N03A X16 Pregabalin 3,876.92 17,637.52 21,514.44 43 B01A B01 Heparin 17,422.15 3,770.18 21,192.33 44 J05A F10 Entecavir 4,298.05 16,653.33 20,951.39 45 A02B A02 Ranitidine 14,521.77 6,326.23 20,848.00 46 C07A B07 Bisoprolol 3,239.94 17,281.83 20,521.77 47 J01F A10 Azithromycin 1,004.26 19,476.56 20,480.82 48 R05C A10 Expectorants, combinations 0.00 20,436.43 20,436.43 49 N05A H04 Quetiapine 16,716.60 3,614.17 20,330.78 50 J01D H02 Meropenem 4,670.32 15,469.62 20,139.94

The Malaysia National Health Accounts (MNHA) framework reported the total expenditure on health (TEH) in Malaysia for the year 2017 was at MYR 57,361 million which accounted for 4.24% of gross domestic product (GDP). The MHNA report stated that the Ministry of Health (MoH) alone has spent MYR 3.6 million in year 1997 and this amount increased steeply to MYR 24.7 million in year 2017 which constituted about 43% of TEH of the respective years. In relation to GDP, the MoH expenditure specifically has taken up about 1.83% out of the 4.24% Malaysian GDP accounted for TEH in year 2017. Approximately 10% of total MoH expenditure was the pharmaceuticals.1

This chapter assesses drug expenditure for the year 2015 and 2016. The total estimated drug expenditure reported in Malaysia has increased by 2.3% from MYR 5.2 billion in 2015 to MYR 5.3 billion in 2016 as shown in Figure 3.1. This increment was mainly contributed by the drug expenditure in the private sector which reported an increment of 5.6%. In contrast, a slight decrement of 2.8% was observed in the public sector and this was closely related to the marginal shrinkage of the yearly budget allocation in the public sector. It is important to note that pharmaceutical expenditure by the public sector reported here is lower than officially reported expenditure as there are several categories of drugs excluded in the report as stated in Chapter 1.

6,000.00 5,362.35 5,239.18

5,000.00 4,694.11 4,391.71 4,484.91

3,790.05 4,000.00 3,374.54 3,195.09

3,000.00 2,610.20 2,404.07 2,505.07 2,170.82

2,000.00 1,987.64 1,979.84 2,083.91 2,044.09 1,987.81 1,619.23 1,000.00

Expenditure on medicines (MYR (MYR '000,000) on medicinesExpenditure 0.00 2011 2012 2013 2014 2015 2016 Private Public Public + Private

Figure 3.1 Estimated total expenditure on medicines from 2011 to 2016 between public and private sector, and in total (MYR ‘000,000)

The top ten therapeutic groups contributed to the highest drug expenditures in 2015 amounted to MYR 2.4 billion and this attributed to 46% of the total expenditure for that year. In the following year, the expenditure of these therapeutic groups amounted to MYR 2.5 billion and this is attributed to 47% of the expenditure for that year. Drugs used in diabetes (A10) was ranked the highest both in 2015 and 2016, followed by antibacterials for systemic use (J01). These two therapeutic groups contributed up to 15% of the total expenditure in 2016 for public sector. Comparing between year 2015 and 2016 in public sector, the highest increase in expenditure was observed for antineoplastic agents (L01) at 17.9%. Other therapeutic groups that are in the top ten list included drugs for blood and blood forming agents (B05), vaccines (J07), antithrombotic agents (B01), psycholeptics (N05), drugs acting on the renin-angiotensin system (C09), lipid modifying agents (C10) and immunosuppressants (L04).

Further analyses comparing expenditure in 2015 versus 2016 within public and private sectors reported that the highest expenditure in the public sector for both years were drugs used in diabetes (A01). Whereas in the private sector, the antibacterials for systemic use (J01) topped the list. Drugs used in diabetes (A10), antibacterials for systemic use (J01) and antineoplastic agents (L01) was in the public sector list of top-ten therapeutic groups which was also seen in the private sector. These similarities may be due to the prevelance of diseases frequently treated in the two sectors and prescribing pattern within the therapeutic groups.1

An increasing trend in expenditure from year 2015 to 2016 was observed in the public sector for blood substitutes and perfusion solutions (B05), followed by lipid modifying agent (C10), antineoplastic agents (L01) and drugs used in diabetes (A10) (Table 3.3). The increase in expenditure for lipid modifying agents may be due to the increase in utilisation of statins to treat the increasing number of diagnosed cases of hypercholesterolaemia. In addition, new strength were added for combination of ezetimibe with simvastatin to the Ministry of Health Medicines Formulary (MoHMF) in 2015. For antineoplastic agents, the increase was possibly driven by the listing of highly priced new innovative drugs including targeted therapy and the addition of new strengths and indications into the MoHMF between 2015 to 2016. Example of such drugs are bendamustine hydrochloride and sunitinib malate, whereby both drugs were listed in MoHMF in 2016. For bortezomib, new indications were added to the MoHMF in 2015 and new strength for trastuzumab and erlotinib was added in 2016. The increasing trend in expenditure for drugs used in diabetes (A10) may also be caused by the addition of new strength for insulin lispro in 2016 MoHMF.

Table 3.3 Top 10 expenditure on medicines by therapeutic groups in 2016 compared to 2015 (MYR `000,000) Sector ATC Therapeutic group 2015 2016 Changes code Expenditure Rank Expenditure Rank from 2015 (%)

Public A10 Drugs used in diabetes 410.23 2 455.69 1 11.1 and J01 Antibacterials for systemic 415.72 1 408.20 2 -1.8 private use L01 Antineoplastic agents 245.12 4 290.91 3 18.7 C09 Agents acting on the renin- 235.21 5 250.75 4 6.6 angiotensin system C10 Lipid modifying agents 247.33 3 245.79 5 -0.6 J07 Vaccines 206.28 6 210.97 6 2.3 A02 Drugs for acid related 184.22 7 189.28 7 2.7 disorders B01 Antithrombotic agents 175.34 9 182.82 8 4.3 M01 Antiinflammatory and 175.96 8 176.55 9 0.3 antirheumatic products R03 Drugs for obstructive airway 161.35 10 155.48 10 -3.6 diseases Public A10 Drugs used in diabetes 192.39 1 214.19 1 11.3 J01 Antibacterials for systemic 152.55 2 136.36 2 -10.6 use L01 Antineoplastic agents 114.24 3 134.71 3 17.9 B05 Blood substitutes and 69.05 8 115.03 4 66.6 perfusion solutions J07 Vaccines 103.01 4 98.36 5 -4.5 B01 Antithrombotic agents 77.18 6 74.77 6 -3.1 N05 Psycholeptics 78.30 5 73.45 7 -6.2 C09 Agents acting on the renin- 56.97 9 60.55 8 6.3 angiotensin system C10 Lipid modifying agents 73.10 7 59.41 9 -18.7 L04 Immunosuppressants 57.14 10 57.06 10 -0.1 Private J01 Antibacterials for systemic 263.17 1 271.84 1 3.3 use A10 Drugs used in diabetes 217.83 2 241.49 2 10.9 C09 Agents acting on the renin- 178.23 3 190.20 3 6.7 angiotensin system C10 Lipid modifying agents 174.24 4 186.38 4 7.0 M01 Antiinflammatory and 158.17 5 157.97 5 -0.1 antirheumatic products L01 Antineoplastic agents 130.89 7 156.20 6 19.3 A02 Drugs for acid related 135.84 6 145.90 7 7.4 disorders J07 Vaccines 103.26 8 112.62 8 9.1 B01 Antithrombotic agents 98.16 10 108.05 9 10.1 R03 Drugs for obstructive airway 101.85 9 102.51 10 0.6 diseases

Table 3.3 shows the highest increase was seen in lipid modifying agent, drugs used in diabetes and vaccines in private sector. The upward trend of expenditure was likely contributed by the steady increase in utilisation of drugs in these therapeutic groups influenced by the prevalence of cardiovascular diseases, diabetes and also seasonal outbreaks of infectious diseases which required vaccinations.

The reported average public sector share of drug expenditure in 2015 and 2016 was 39% and 37%, respectively. Throughout the years, statistics indicate that the public sector has managed to provide wider coverage of medicines at lower prices possibly due to effective procurement strategies.2

For drugs used in diabetes (A10), metformin (A10B A02) contributed to the highest expenditure mainly in the public sector followed by gliclazide (A10B B09) in both sectors while combination of metformin and sitagliptin (A10B D07) was highest in the private sector. For lipid modifying agents, the highest contributor was the statin group specifically referring to atorvastatin (C10A A05) in the private sector followed by simvastatin (C10A A01) in the public sector and rosuvastatin (C10A A07) in the private sector.

The top-five drugs with the highest expenditure between 2015 and 2016 were metformin (A10B A02), erythropoietin (B03X A01), gliclazide (A10B B09), diphtheria-hemophilus influenzae B-pertussis-poliomyelitis- tetanus vaccine (J07C A06), and atorvastatin (C10A A05). In 2015, a total of MYR 387 million was spent on these drugs contributing to approximately 7% of the total expenditure. For metformin (A10B A02), erythropoietin (B03X A01) and gliclazide (A10B B09), the expenditure was mainly contributed by the public sector. Different expenditure trend was seen in Australia in which the top-five drugs by expenditure were reported to be esomeprazole (A02B C05), combination of salmeterol and fluticasone (R03A K06), rosuvastatin (C10A A07), pregabalin (N03A X16), adalimumab (L04A B04) and atorvastatin (C10A A05).

Overall, there is an increasing trend of expenditure over the years contributed by the increased burden of diseases particularly non-communicable diseases, increase in ageing population and emergent of newly innovative therapies.1

REFERENCES

1. Malaysia National Health Accounts: Health Expenditure Report 1997- 2017; Planning Division, Ministry of Health Malaysia: Putrajaya, 2019. 2. Malaysian National Medicines Policy 2nd Edition 2012; Dasar Ubat Nasional, Edisi Kedua, 2012; Pharmaceutical Services Division, Ministry of Health Malaysia: Kuala Lumpur, 2013.

4 Alimentary Tract and Metabolism

Statistics on medicines for alimentary tract and metabolism 4.1

Table 4.1 Statistics by therapeutic groups for alimentary tract and metabolism, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

A Alimentary tract and 81.6833 38.6494 120.3327 78.5883 38.0317 116.6200 metabolism

A02 Drugs for acid related disorders 7.2656 3.7382 11.0038 6.9301 3.6746 10.6047 A03 Drugs for functional 0.7283 2.0165 2.7448 0.4834 1.7039 2.1873 gastrointestinal disorders A04 Antiemetics and antinauseants 0.0097 0.0104 0.0200 0.0128 0.0117 0.0245 A05 Bile and liver therapy 0.0115 0.0231 0.0346 0.0055 0.0202 0.0257 A06 Drugs for constipation 0.7783 1.5965 2.3748 1.0752 1.5805 2.6556 A07 Antidiarrheals, intestinal 0.2890 0.6690 0.9580 0.2799 0.6942 0.9741 antiinflammatory/antiinfective agents A08 Antiobesity preparations, 0.0028 0.5394 0.5422 0.0008 0.4575 0.4583 excluding diet products A10 Drugs used in diabetes 63.7128 11.3484 75.0611 61.9611 11.3131 73.2742 A11 Vitamins 5.4220 18.0759 23.4979 4.7050 18.1011 22.8061 A12 Mineral supplements 3.4623 0.5894 4.0517 3.1342 0.4378 3.5721 A14 Anabolic agents for systemic 0.0001 - 0.0001 0.0001 - 0.0001 use A16 Other alimentary tract and 0.0009 0.0426 0.0435 0.0002 0.0371 0.0373 metabolism products

Table 4.2 Drugs for acid related disorders, A02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A02B Drugs for peptic ulcer and 7.2656 3.7382 11.0038 6.9301 3.6746 10.6047 gastro-oesophageal reflux disease (GORD)

A02B A H2-receptor antagonists 3.7358 0.8488 4.5846 3.3000 0.7153 4.0153 A02B A01 Cimetidine - 0.1658 0.1658 - 0.1641 0.1641 A02B A02 Ranitidine 3.7358 0.4796 4.2154 3.3000 0.3206 3.6206 A02B A03 Famotidine - 0.2034 0.2034 - 0.2306 0.2306

A02B B Prostaglandins 0.0001 0.0074 0.0075 0.0003 0.0049 0.0052 A02B B01 Misoprostol 0.0001 0.0074 0.0075 0.0003 0.0049 0.0052

A02B C Proton pump inhibitors 3.5291 2.8435 6.3725 3.6294 2.9172 6.5466 A02B C01 Omeprazole 2.4556 0.8574 3.3130 2.2826 0.8608 3.1434 A02B C02 Pantoprazole 0.7027 0.7876 1.4904 0.9729 0.8655 1.8384 A02B C03 Lansoprazole 0.0377 0.1931 0.2308 0.0406 0.1199 0.1605 A02B C04 Rabeprazole 0.0097 0.1519 0.1616 0.0198 0.1735 0.1933 A02B C05 Esomeprazole 0.3225 0.6858 1.0083 0.3124 0.6477 0.9600 A02B C06 Dexlansoprazole 0.0008 0.1676 0.1684 0.0010 0.2499 0.2509

A02B D Combinations for eradication - 0.0212 0.0212 - 0.0207 0.0207 of Helicobacter pylori A02B D00 Omeprazole, clarithromycin - 0.0024 0.0024 - 0.0002 0.0002 and tinidazole A02B D05 Omeprazole, amoxicillin and - 0.0188 0.0188 - 0.0205 0.0205 clarithromycin

A02B X Other drugs for peptic ulcer 0.0006 0.0173 0.0179 0.0005 0.0165 0.0170 and gastro-oesophageal reflux disease (GORD) A02B X02 Sucralfate 0.0005 0.0001 0.0006 0.0003 0.0004 0.0007 A02B X14 Rebamipide 0.0002 0.0172 0.0173 0.0002 0.0160 0.0162

Table 4.3 Drugs for functional gastrointestinal disorders, A03 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A03A Drugs for functional 0.0228 0.3599 0.3827 0.0110 0.3827 0.3937 gastrointestinal disorders

A03A A Synthetic anticholinergics, 0.0191 0.0695 0.0886 0.0070 0.0699 0.0770 esters with tertiary amino group A03A A04 Mebeverine 0.0191 0.0659 0.0850 0.0070 0.0684 0.0755 A03A A05 Trimebutine - 0.0012 0.0012 - <0.0001 <0.0001 A03A A07 Dicycloverine - 0.0024 0.0024 - 0.0015 0.0015

A03A B Synthetic anticholinergics, 0.0023 0.0009 0.0032 0.0034 0.0011 0.0045 quaternary ammonium compounds A03A B02 Glycopyrronium bromide 0.0023 0.0009 0.0032 0.0034 0.0011 0.0045

A03A D Papaverine and derivatives <0.0001 0.0603 0.0603 0.0001 0.0999 0.0999 A03A D01 Papaverine <0.0001 - <0.0001 0.0001 - 0.0001 A03A D02 Drotaverine - 0.0603 0.0603 - 0.0999 0.0999

Table 4.3 (continued) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A03A X Other drugs for functional 0.0014 0.2292 0.2305 0.0005 0.2118 0.2123 gastrointestinal disorders A03A X04 Pinaverium 0.0001 0.0118 0.0119 - 0.0132 0.0132 A03A X13 Silicones 0.0001 0.1628 0.1630 0.0001 0.1460 0.1461 A03A X58 Alverine, combinations 0.0012 0.0545 0.0557 0.0004 0.0526 0.0530

A03B Belladonna and derivatives, 0.2192 0.4835 0.7026 0.1796 0.3962 0.5758 plain

A03B A Belladonna alkaloids, tertiary 0.0313 0.0087 0.0400 0.0245 0.0063 0.0308 amines A03B A01 Atropine 0.0313 0.0087 0.0400 0.0245 0.0063 0.0308

A03B B Belladonna alkaloids, 0.1879 0.4748 0.6626 0.1551 0.3899 0.5450 semisynthetic, quaternary ammonium compounds A03B B01 Butylscopolamine 0.1879 0.4748 0.6626 0.1551 0.3899 0.5450

A03C Antispasmodics in - 0.0277 0.0277 - 0.0288 0.0288 combination with psycholeptics

A03C A Synthetic anticholinergic - 0.0277 0.0277 - 0.0288 0.0288 agents in combination with psycholeptics A03C A02 Clidinium and psycholeptics - 0.0277 0.0277 - 0.0288 0.0288

A03E Antispasmodics and - 0.0598 0.0598 - 0.0740 0.0740 anticholinergics in combination with other drugs

A03E D Antispasmodics in - 0.0598 0.0598 - 0.0740 0.0740 combination with other drugs

A03F Propulsives 0.4864 1.0856 1.5720 0.2927 0.8221 1.1149

A03F A Propulsives 0.4864 1.0856 1.5720 0.2927 0.8221 1.1149 A03F A01 Metoclopramide 0.4039 0.3549 0.7589 0.2190 0.2429 0.4619 A03F A03 Domperidone 0.0536 0.6099 0.6635 0.0379 0.4395 0.4775 A03F A07 Itopride 0.0288 0.1208 0.1496 0.0358 0.1397 0.1755

Table 4.4 Antiemetics and antinauseants, A04 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A04A Antiemetics and antinauseants 0.0097 0.0104 0.0200 0.0128 0.0117 0.0245

A04A A Serotonin (5HT3) antagonists 0.0088 0.0083 0.0171 0.0125 0.0094 0.0219 A04A A01 Ondansetron 0.0011 0.0031 0.0042 0.0009 0.0032 0.0041 A04A A02 Granisetron 0.0078 0.0039 0.0116 0.0116 0.0047 0.0162 A04A A05 Palonosetron <0.0001 0.0013 0.0013 <0.0001 0.0015 0.0016

A04A D Other antiemetics 0.0008 0.0021 0.0029 0.0004 0.0022 0.0026 A04A D12 Aprepitant 0.0008 0.0021 0.0029 0.0004 0.0022 0.0026

Table 4.5 Bile and liver therapy, A05 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A05A Bile therapy 0.0115 0.0231 0.0346 0.0055 0.0202 0.0257

A05A A Bile acids and derivatives 0.0115 0.0231 0.0346 0.0055 0.0202 0.0257 A05A A02 Ursodeoxycholic acid 0.0115 0.0231 0.0346 0.0055 0.0202 0.0257

Table 4.6 Drugs for constipation, A06 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A06A Drugs for constipation 0.7783 1.5965 2.3748 1.0752 1.5805 2.6556

A06A A Softeners, emollients - 0.0001 0.0001 - 0.0001 0.0001 A06A A02 Docusate sodium - 0.0001 0.0001 - 0.0001 0.0001

A06A B Contact laxatives 0.1691 0.9737 1.1428 0.1343 1.0124 1.1467 A06A B02 Bisacodyl 0.1691 0.9737 1.1428 0.1343 1.0124 1.1467

A06A D Osmotically acting laxatives 0.6091 0.6110 1.2200 0.9408 0.5563 1.4971 A06A D11 Lactulose 0.6063 0.5219 1.1282 0.9376 0.4786 1.4162 A06A D15 Macrogol 0.0004 0.0869 0.0873 - 0.0756 0.0756 A06A D17 Sodium phosphate 0.0024 0.0021 0.0045 0.0031 0.0021 0.0053

A06A X Other drugs for constipation 0.0001 0.0117 0.0118 0.0001 0.0116 0.0117 A06A X05 Prucalopride 0.0001 0.0117 0.0118 0.0001 0.0116 0.0117

Table 4.7 Antidiarrheals, intestinal antiinflammatory/antiinfective agents, A07 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A07A Intestinal antiinfectives 0.0204 0.0086 0.0290 0.0158 0.0082 0.0240

A07A A Antibiotics 0.0204 0.0086 0.0290 0.0158 0.0082 0.0240 A07A A02 Nystatin 0.0204 0.0086 0.0290 0.0158 0.0082 0.0240

A07B Intestinal adsorbents 0.0116 0.1584 0.1700 0.0130 0.1484 0.1614

A07B A Charcoal preparations 0.0113 0.0535 0.0648 0.0129 0.0505 0.0635 A07B A01 Medicinal charcoal 0.0113 0.0533 0.0647 0.0129 0.0505 0.0635 A07B A51 Medicinal charcoal, - 0.0001 0.0001 - - - combinations

A07B C Other intestinal adsorbents 0.0003 0.1049 0.1051 0.0001 0.0979 0.0979 A07B C05 Diosmectite 0.0003 0.1049 0.1051 0.0001 0.0979 0.0979

A07D Antipropulsives 0.0998 0.4647 0.5645 0.0973 0.4989 0.5962

A07D A Antipropulsives 0.0998 0.4647 0.5645 0.0973 0.4989 0.5962 A07D A01 Diphenoxylate 0.0905 0.2800 0.3704 0.0772 0.3056 0.3828 A07D A03 Loperamide 0.0093 0.1847 0.1941 0.0202 0.1933 0.2135

A07E Intestinal antiinflammatory 0.1572 0.0373 0.1945 0.1538 0.0387 0.1925 agents

A07E C Aminosalicylic acid and 0.1572 0.0373 0.1945 0.1538 0.0387 0.1925 similar agents A07E C01 Sulfasalazine 0.1290 0.0164 0.1454 0.1278 0.0138 0.1416 A07E C02 Mesalazine 0.0282 0.0209 0.0491 0.0260 0.0249 0.0508

Table 4.8 Antiobesity preparations, excluding diet products, A08 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A08A Antiobesity preparations, 0.0028 0.5394 0.5422 0.0008 0.4575 0.4583 excluding diet products

A08A A Centrally acting antiobesity 0.0022 0.3382 0.3404 0.0003 0.2538 0.2542 products A08A A01 Phentermine 0.0022 0.3382 0.3404 0.0003 0.2538 0.2542

A08A B Peripherally acting antiobesity 0.0006 0.2012 0.2018 0.0005 0.2036 0.2041 products A08A B01 Orlistat 0.0006 0.2012 0.2018 0.0005 0.2036 0.2041

Table 4.9 Insulins and analogues, A10A (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A10A Insulins and analogues 7.4050 0.6048 8.0097 10.7562 0.6472 11.4034

A10A B Insulins and analogues for 2.0823 0.1036 2.1859 3.2023 0.1139 3.3162 injection, fast-acting A10A B01 Insulin (human), fast-acting 1.9873 0.0082 1.9955 3.0928 0.0083 3.1011 A10A B04 Insulin lispro, fast-acting 0.0115 0.0069 0.0184 0.0089 0.0066 0.0155 A10A B05 Insulin aspart, fast-acting 0.0815 0.0826 0.1641 0.0998 0.0915 0.1913 A10A B06 Insulin glulisine, fast-acting 0.0019 0.0060 0.0079 0.0007 0.0075 0.0082

A10A C Insulins and analogues for 2.0417 0.0055 2.0473 2.5525 0.0050 2.5574 injection, intermediate-acting A10A C01 Insulin (human), intermediate- 2.0417 0.0055 2.0473 2.5525 0.0050 2.5574 acting

A10A D Insulins and analogues for 3.1568 0.3509 3.5076 4.8734 0.3622 5.2356 injection, intermediate- or long-acting combined with fast-acting A10A D01 Insulin (human), intermediate- 3.0917 0.0308 3.1224 4.7343 0.0292 4.7635 or long-acting combined with fast-acting A10A D04 Insulin lispro, intermediate- or 0.0112 0.0436 0.0548 0.0110 0.0460 0.0569 long-acting combined with fast-acting A10A D05 Insulin aspart, intermediate- or 0.0539 0.2765 0.3304 0.1281 0.2870 0.4151 long-acting combined with fast-acting

A10A E Insulins and analogues for 0.1242 0.1448 0.2690 0.1281 0.1661 0.2942 injection, long-acting A10A E04 Insulin glargine 0.1002 0.0952 0.1954 0.1066 0.1161 0.2227 A10A E05 Insulin detemir 0.0240 0.0496 0.0736 0.0215 0.0500 0.0714

Table 4.10 Blood glucose lowering drugs, excluding insulins, A10B (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A10B Blood glucose lowering drugs, 56.3078 10.7436 67.0514 51.2049 10.6659 61.8708 excluding insulins

A10B A Biguanides 16.6506 3.0228 19.6733 15.4539 2.3545 17.8084 A10B A02 Metformin 16.6506 3.0228 19.6733 15.4539 2.3545 17.8084

A10B B Sulfonylureas 36.7087 4.6465 41.3552 32.6199 4.7659 37.3858 A10B B01 Glibenclamide 2.0028 0.7251 2.7279 1.1987 0.5966 1.7953 A10B B07 Glipizide 0.0006 0.0261 0.0267 - 0.0284 0.0284 A10B B09 Gliclazide 34.6899 3.5650 38.2548 31.4109 3.8507 35.2616 A10B B12 Glimepiride 0.0155 0.3303 0.3457 0.0103 0.2902 0.3004

A10B D Combinations of oral blood 2.1029 2.2578 4.3606 2.4234 2.4778 4.9012 glucose lowering drugs A10B D02 Metformin and sulfonylureas 2.0222 0.8437 2.8659 2.3387 0.8232 3.1619 A10B D03 Metformin and rosiglitazone 0.0009 0.0007 0.0016 - - - A10B D07 Metformin and sitagliptin 0.0357 0.6800 0.7157 0.0367 0.7722 0.8089 A10B D08 Metformin and vildagliptin 0.0366 0.3355 0.3721 0.0435 0.3602 0.4037 A10B D10 Metformin and saxagliptin 0.0056 0.2428 0.2485 0.0028 0.2714 0.2743 A10B D11 Metformin and linagliptin 0.0018 0.1550 0.1569 0.0017 0.2153 0.2171 A10B D15 Metformin and dapagliflozin - - - - 0.0354 0.0354

A10B F Alpha glucosidase inhibitors 0.6686 0.0544 0.7230 0.4390 0.0541 0.4931 A10B F01 Acarbose 0.6686 0.0544 0.7230 0.4390 0.0541 0.4931

A10B G Thiazolidinediones 0.0086 0.0244 0.0330 0.0048 0.0276 0.0324 A10B G02 Rosiglitazone 0.0068 0.0012 0.0080 0.0024 0.0001 0.0024 A10B G03 Pioglitazone 0.0018 0.0233 0.0250 0.0025 0.0275 0.0300

A10B H Dipeptidyl peptidase 4 (DPP-4) 0.1547 0.4782 0.6329 0.2516 0.4829 0.7345 inhibitors A10B H01 Sitagliptin 0.0472 0.2205 0.2678 0.0698 0.2149 0.2847 A10B H02 Vildagliptin 0.0033 0.0419 0.0453 0.0066 0.0423 0.0489 A10B H03 Saxagliptin 0.0809 0.0350 0.1158 0.1493 0.0287 0.1780 A10B H05 Linagliptin 0.0232 0.1808 0.2040 0.0258 0.1970 0.2228

A10B J Glucagon-like peptide-1 0.0047 0.0323 0.0370 0.0033 0.0332 0.0365 (GLP-1) analogues A10B J01 Exenatide - <0.0001 <0.0001 0.0001 0.0040 0.0042 A10B J02 Liraglutide 0.0047 0.0323 0.0370 0.0032 0.0292 0.0323

A10B K Sodium-glucose co- 0.0049 0.2173 0.2222 0.0067 0.4589 0.4657 transporter 2 (SGLT2) inhibitors A10B K01 Dapagliflozin 0.0049 0.2173 0.2222 0.0043 0.2531 0.2574 A10B K02 Canagliflozin - - - - 0.0083 0.0083 A10B K03 Empagliflozin - - - 0.0024 0.1976 0.2000

A10B X Other blood glucose lowering 0.0042 0.0099 0.0141 0.0023 0.0110 0.0133 drugs, excluding insulins A10B X02 Repaglinide 0.0042 0.0096 0.0138 0.0023 0.0110 0.0133 A10B X03 Nateglinide - 0.0003 0.0003 - - -

Table 4.11 Vitamins, A11 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A11C Vitamin A and D, including 1.1026 0.4612 1.5638 1.0337 0.4540 1.4878 combinations of the two

A11C C Vitamin D and analogues 1.1026 0.4612 1.5638 1.0337 0.4540 1.4878 A11C C03 Alfacalcidol 0.2737 0.0163 0.2900 0.2580 0.0076 0.2656 A11C C04 Calcitriol 0.7984 0.0776 0.8761 0.7716 0.0782 0.8498 A11C C05 Colecalciferol 0.0304 0.3673 0.3977 0.0042 0.3682 0.3724

A11D Vitamin B1, plain and in 0.1394 0.0214 0.1608 0.1257 0.0083 0.1340 combination with vitamin B6 and B12

A11D A Vitamin B1, plain 0.1394 0.0214 0.1608 0.1257 0.0083 0.1340 A11D A01 Thiamine (vitamin B1) 0.1394 0.0214 0.1608 0.1257 0.0083 0.1340

A11G Ascorbic acid (vitamin C), 4.1403 16.6953 20.8356 3.5163 16.7489 20.2653 including combinations

A11G A Ascorbic acid (vitamin C), 4.1403 16.6953 20.8356 3.5163 16.7489 20.2653 plain A11G A01 Ascorbic acid (vitamin C) 4.1403 16.6953 20.8356 3.5163 16.7489 20.2653

A11H Other plain vitamin 0.0396 0.8980 0.9377 0.0292 0.8899 0.9191 preparations

A11H A Other plain vitamin 0.0396 0.8980 0.9377 0.0292 0.8899 0.9191 preparations A11H A02 Pyridoxine (vitamin B6) 0.0396 0.0127 0.0524 0.0292 0.0116 0.0408 A11H A03 Tocopherol (vitamin E) - 0.8853 0.8853 - 0.8782 0.8782

Table 4.12 Mineral supplements, A12 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A12A Calcium 2.2679 0.2661 2.5339 2.0877 0.1784 2.2661

A12A A Calcium 2.2679 0.2661 2.5339 2.0877 0.1784 2.2661 A12A A03 Calcium gluconate 0.0054 0.0005 0.0060 0.0027 0.0004 0.0031 A12A A04 Calcium carbonate 0.8378 0.0617 0.8996 0.8772 0.0671 0.9443 A12A A05 Calcium lactate 1.4246 0.2038 1.6284 1.2078 0.1109 1.3187

A12B Potassium 0.9925 0.2946 1.2871 0.8781 0.2509 1.1289

A12B A Potassium 0.9925 0.2946 1.2871 0.8781 0.2509 1.1289 A12B A01 Potassium chloride 0.7231 0.1246 0.8477 0.6488 0.1139 0.7627 A12B A02 Potassium citrate 0.2695 0.1699 0.4394 0.2293 0.1370 0.3663

A12C Other mineral supplements 0.2019 0.0288 0.2307 0.1685 0.0085 0.1770

A12C B Zinc - 0.0003 0.0003 - 0.0008 0.0008 A12C B01 Zinc sulfate - 0.0003 0.0003 - 0.0008 0.0008

A12C C Magnesium 0.2019 0.0285 0.2304 0.1685 0.0077 0.1762 A12C C02 Magnesium sulfate 0.2019 0.0285 0.2304 0.1685 0.0077 0.1762

Table 4.13 Anabolic agents for systemic use, A14 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A14A Anabolic steroids 0.0001 - 0.0001 0.0001 - 0.0001

A14A A Androstan derivatives 0.0001 - 0.0001 0.0001 - 0.0001 A14A A05 Oxymetholone 0.0001 - 0.0001 0.0001 - 0.0001

Table 4.14 Other alimentary tract and metabolism products, A16 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

A16A Other alimentary tract and 0.0009 0.0426 0.0435 0.0002 0.0371 0.0373 metabolism products

A16A A Amino acids and derivatives 0.0008 0.0125 0.0134 0.0002 0.0080 0.0082 A16A A01 Levocarnitine 0.0008 0.0125 0.0134 0.0002 0.0080 0.0082

A16A B Enzymes 0.0001 - 0.0001 - - - A16A B05 Laronidase <0.0001 - <0.0001 - - - A16A B07 Alglucosidase alfa 0.0001 - 0.0001 - - -

A16A X Various alimentary tract and <0.0001 0.0300 0.0300 <0.0001 0.0291 0.0291 metabolism products A16A X01 Thioctic acid - 0.0300 0.0300 - 0.0291 0.0291 A16A X03 Sodium phenylbutyrate <0.0001 - <0.0001 <0.0001 - <0.0001 A16A X05 Zinc acetate <0.0001 - <0.0001 - - -

Utilisation of drugs for alimentary disorders 4.2 Rosaida Md Said, Zalwani Zainuddin, Norasiah Abu Bakar, Tan Soek Siam, Muhammad Radzi Abu Hassan

Acid-related gastrointestinal diseases comprise a variety of disorders that affect the oesophagus, stomach and duodenum. The common causes of acid related disorders are peptic ulcer disease (PUD) and gastro-oesophageal reflux disease (GORD). Goh et al reported that the prevalence of duodenal ulcer, gastric ulcer and GORD in Malaysia is 9.5%, 9.4% and 8.4%, respectively.1 Even though the prevalence of GORD in Asian countries is lower compared to developed nations, the prevalence is steadily rising.2,3 Malaysian data shows that the prevalence of GORD to be between 0.9% and 13.4%4,5 whereas a study in the United States shows up to 44% of adults experiencing it at least once monthly.6

The total utilisation of medicines for acid-related disorders in year 2016 has reduced, from 11.0038 in 2015 to 10.6047 DDD/1,000 inhabitants/day mainly attributed to the decrease usage of H2-receptor antagonists (H2RA). The use of H2RA has reduced from 4.5846 DDD/1,000 inhabitants/day in year 2015 to 4.0153 DDD/1,000 inhabitants/day in year 2016, and was observed both in public and private sectors, which could be explained by the availability of proton-pump inhibitors (PPI), a more potent acid suppressive medicine. The most widely prescribed H2RA for both years was ranitidine, whereas cimetidine and famotidine were no longer being prescribed in the public sector.

The trend of usage of PPIs did show an increase from 6.3725 to 6.5466 DDD/1,000 inhabitants/day, in year 2015 and 2016, respectively. PPI is largely being prescribed nowadays for GORD and as prophylaxis to reduce the risk of upper gastro-intestinal bleeding in patients on dual antiplatelets and patients who need non-steroidal anti-inflammatory drugs. The three most widely prescribed PPIs for both years are omeprazole, pantoprazole and esomeprazole. Other PPIs available in Malaysia are lansoprazole, rabeprazole and dexlansoprazole.

Statistics for combined Helicobacter pylori eradication medication were only obtained from the private sector as these medications were not purchased in public sector. The most used combination was omeprazole, amoxicillin and claritromycin.

Sucralfate and rebamipide, two mucosal protective agents were rarely being prescribed. This is because PPI has shown to be much superior in the treatment of PUD and acid-related disorders.

The usage of drugs for functional gastrointestinal disorders has generally been increasing in trend from year 2015 (0.3827 DDD/1,000 inhabitants/day) to year 2016 (0.3937 DDD/1,000 inhabitants/day). The most common drug for functional bowel disorder that has been prescribed was mebeverine in both years.

In the management of motility disorder, metoclopramide remained the most popular drug in year 2015 (0.7589 DDD/1,000 inhabitants/day) as compared to domperidone and itopride. However, this trend has changed in 2016 whereby domperidone (0.4775 DDD/1,000 inhabitants/day) usage was higher than metoclopramide (0.4619 DDD/1,000 inhabitants/day).

In conclusion, PPIs remains the most widely prescribed drugs in the management of acid-related disorders in Malaysia. This may be attributed to a better understanding of the acid-related gastrointestinal diseases and the availability of generic preparations. Despite the availability of newer PPIs, omeprazole and pantoprazole still remain the two most commonly prescribed PPIs, attributed mainly to lower cost of generic formulations, easy accessibility and familiarity with the medicines.

Ranitidine was still widely being used in the public and private sectors. This may be attributed to familiarity with the drugs among prescribers, easy availability, being cost-effective and safe.

For non-acid related diseases, there were not much changes except that itopride has been increasingly being prescribed, especially in the private sector.

Utilisation of antiobesity drugs 4.3 Zanariah Hussein, Nor Afidah Karim, Vijiya Mala Valayatham, Danish Ng Ooi Yee, Wong Hui Chin, Navin Kumar Loganadan, Daphne Gima

The total consumption of antiobesity agents in Malaysia in 2015 and 2016 were 0.5422 and 0.4583 DDD/1,000 inhabitants/day, respectively. Statistics for both years showed an overall decline in the utilisation of antiobesity drugs.

The utilisation of these medicines was extremely low in the public sector (0.5% in 2015 and 0.2% in 2016) compared to usage in private sector (99.5% in 2015 and 99.8% in 2016). Phentermine, the centrally acting antiobesity drug is utilised more commonly than orlistat, a peripherally acting antiobesity drug both in 2015 and 2016 (Table 4.8). The utilisation of phentermine has significantly declined, markedly so in public sector by 86.4%, compared to a 25.0% reduction in the private sector. Similar data for centrally acting antiobesity drug utilisation from Australia and Finland is not available for comparison.

There is no significant change in the utilisation of orlistat in 2015 and 2016 in both the public and private sector. Orlistat is utilised mostly in the private sector (99.7% in 2015 and 99.8% in 2016) than the public sector. However, the utilisation of orlistat in Malaysia’s public sector in 2015 is comparable to the usage in Australia (about 0.00044 DDD/1,000 inhabitants/day).7

The decline in the utilisation rates of antiobesity drugs could be influenced by the drug cost and availability in Malaysia, despite a high prevalence of obesity as reported by the National Health and Morbidity Survey (NHMS) 2015 (47.7% in 2015).8 Currently, there is no antiobesity drug listed in the Ministry of Health Medicines Formulary.

Utilisation of antidiabetic drugs 4.4 Zanariah Hussein, Nor Afidah Karim, Vijiya Mala Valayatham, Danish Ng Ooi Yee, Wong Hui Chin, Navin Kumar Loganadan, Daphne Gima

In general, the utilisation of antidiabetic drugs is higher in public sector compared to private sector, as 80% of patients with diabetes receive treatment from the public sector.

Insulin

There was a drastic increment in the total consumption of insulins and analogues by 42.4% from 2015 to 2016. This increment is mainly contributed by increased utilisation of fast acting human insulin (55.4%) and premixed insulin (49.3%). The higher utilisation of fast-acting insulin compared to basal (intermediate and long-acting) insulin likely indicates preference for intensive insulin regimens. Further analysis of the results showed that in 2016, utilisation of insulin analogues was lower in the public sector compared private sector. This was probably attributed to higher cost and restricted access to insulin analogues. Compared to Finland and Australia, the overall utilisation of insulin in Malaysia was still much lower in 2015 (31.7000 versus 20.2960 versus 8.0097 DDD/1,000 inhabitants/day).7,9

Oral antidiabetic drugs

There is an unexpected overall decline in the utilisation of oral antidiabetic drugs from 2015 to 2016. It is surprising to see a decline in the utilisation of metformin despite it being the first line therapy for diabetes management. The utilisation of sulfonylureas has also showed a decline by 9.6%, possibly due to the introduction of newer antidiabetic drugs like dipeptidyl peptidase-4 (DPP-4) inhibitors and restriction in the utilisation of some sulfonylureas in the elderly. The utilisation of DPP-4 inhibitors has increased by 16.1%, with sitagliptin as the most commonly prescribed DPP-4 inhibitor since it was the first DPP-4 inhibitor to be introduced in Malaysia.

There is also a slight increase in the utilisation of fixed-dose combinations (FDCs) containing metformin. The utilisation of acarbose has reduced by 31.8% possibly due to unfavourable side effects and frequent dosing. The overall utilisation of thiazolidinediones remains low with 70% reduction in the utilisation of rosiglitazone. The utilisation of sodium-glucose co-transporter 2 (SGLT-2) inhibitors has increased by 109.6% in 2016 compared to 2015, as empagliflozin and canagliflozin became available in 2016.

Other injectable antidiabetic drugs

The utilisation of glucagon-like peptide-1 (GLP-1) analogues is unchanged and remain low due to high cost and limited accessibility. Liraglutide is more commonly utilised compared to exenatide.

REFERENCES

1. Goh, K. L.; Wong, H. T.; Lim, C. H.; Rosaida M. S. Time Trends in Peptic Ulcer, Erosive Reflux Oesophagitis, Gastric and Oesophageal Cancers in a Multiracial Asian Population. Aliment. Pharmacol. Ther. 2009, 29(7), 774-780. 2. Dent, J.; El-Serag, H. B.; Wallander, M. A.; Johansson, S. Epidermiology of Gastro-Oesophageal Reflux Disease: a Systematic Review. Gut 2005, 54(5), 710-717. 3. Goh, K. L.; Chang, C. S.; Fock, K. M.; et al. Gastro-Oesophageal Reflux Disease in Asia. J. Gastroenterol. Hepatol. 2000, 15(3), 230-238. 4. Goh, K. L. Prevalence of and Risk Factors for Helicobaccter pylori in a Multiracial Population Undergoing Endoscopy. J. Gastroenterol. Hepatol. 1997, 12, S29-35. 5. Rosaida M. S.; Goh, K. L. Gastroesophageal Reflux Disease, Reflux Oesophagitis and Non Erosive Reflux Disease in a Multiracial Asian Population: a Prospective Endoscopy Based Study. Eur. J. Gastroenterol. Hepatol. 2004, 16, 495-501. 6. Locke, G. R. 3rd; Talley, N. J.; Fett, S. L.; et al. Prevalence and Clinical Spectrum of Gastro- Oesophageal Reflux: a Population Based Study in Olmsted County. Minnesota Gastroenterology 1997, 112, 1448-1456. 7. Australian Statistics on Medicines 2015; Pharmaceutical Benefit Scheme, Department of Health: Canberra, 2016. http://www.pbs.gov.au/info/statistics/asm/asm-2015. 8. Volume II: Non-Communicable Disease, Risk Factors and Other Health Problems. National Health and Morbidity Survey 2015; National Institutes of Health, Ministry of Health Malaysia: Kuala Lumpur, 2015. 9. Finnish Statistics on Medicines 2015; Finnish Medicines Agency and Social Insurance Institution: Helsinki, 2016.

5 Medicines for Blood and Blood Forming Organs

Statistics on medicines for blood and blood forming organs 5.1

Table 5.1 Statistics by therapeutic groups for blood and blood forming organs, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

B Blood and blood forming 24.0060 7.4527 31.4586 23.1605 7.7782 30.9387 organs

B01 Antithrombotic agents 10.1636 4.1843 14.3480 10.5104 4.3203 14.8307 B02 Antihemorrhagics 0.0631 0.0264 0.0895 0.0540 0.0229 0.0768 B03 Antianemic preparations 13.7792 3.2419 17.0211 12.5961 3.4350 16.0311

Table 5.2 Antithrombotic agents, B01 (Utilisation in DDD/1,000 inhabitants/day). Report on the utilisation of antithrombotic agents is included in Chapter 6. ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

B01A Antithrombotic agents 10.1636 4.1843 14.3480 10.5104 4.3203 14.8307

B01A A Vitamin K antagonists 0.2792 0.0680 0.3472 0.2852 0.0591 0.3443 B01A A03 Warfarin 0.2792 0.0680 0.3472 0.2852 0.0591 0.3443

B01A B Heparin group 0.4269 0.1280 0.5549 0.4108 0.1388 0.5496 B01A B01 Heparin 0.3083 0.0852 0.3935 0.2936 0.0969 0.3905 B01A B05 Enoxaparin 0.0987 0.0126 0.1113 0.0986 0.0137 0.1123 B01A B10 Tinzaparin 0.0195 0.0007 0.0201 0.0184 0.0009 0.0193 B01A B11 Sulodexide 0.0004 0.0295 0.0300 0.0002 0.0272 0.0275

B01A C Platelet aggregation inhibitors 9.3777 3.8538 13.2315 9.7405 3.9430 13.6835 excluding heparin B01A C04 Clopidogrel 0.6856 1.2635 1.9491 0.6873 1.4428 2.1301 B01A C05 Ticlopidine 0.3674 0.0509 0.4183 0.4728 0.0497 0.5225 B01A C06 Acetylsalicylic acid 8.2776 2.3874 10.6650 8.5408 2.2761 10.8170 B01A C07 Dipyridamole 0.0315 0.0005 0.0321 0.0219 - 0.0219 B01A C11 Iloprost <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 B01A C13 Abciximab <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 B01A C17 Tirofiban 0.0001 <0.0001 0.0001 <0.0001 <0.0001 0.0001 B01A C18 Triflusal 0.0001 0.0305 0.0306 <0.0001 0.0273 0.0273 B01A C22 Prasugrel 0.0002 0.0083 0.0085 0.0008 0.0075 0.0083 B01A C23 Cilostazol 0.0001 0.0057 0.0058 0.0007 0.0059 0.0066 B01A C24 Ticagrelor 0.0139 0.0722 0.0861 0.0155 0.0891 0.1046 B01A C30 Platelet aggregation inhibitors 0.0012 0.0346 0.0358 0.0006 0.0444 0.0450 excluding heparin, combinations

B01A D Enzymes 0.0010 <0.0001 0.0010 0.0008 <0.0001 0.0008 B01A D01 Streptokinase 0.0008 <0.0001 0.0008 0.0007 <0.0001 0.0007 B01A D02 Alteplase <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 B01A D04 Urokinase <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 B01A D11 Tenecteplase 0.0002 <0.0001 0.0002 0.0001 <0.0001 0.0001

B01A E Direct thrombin inhibitors 0.0361 0.0442 0.0803 0.0312 0.0551 0.0864 B01A E07 Dabigatran etexilate 0.0361 0.0442 0.0803 0.0312 0.0551 0.0864

B01A F Direct factor Xa inhibitors 0.0206 0.0874 0.1080 0.0161 0.1212 0.1372 B01A F01 Rivaroxaban 0.0184 0.0688 0.0872 0.0135 0.0891 0.1026 B01A F02 Apixaban 0.0022 0.0186 0.0208 0.0026 0.0321 0.0346

B01A X Other antithrombotic agents 0.0221 0.0029 0.0250 0.0259 0.0032 0.0291 B01A X05 Fondaparinux 0.0221 0.0029 0.0250 0.0259 0.0032 0.0291

Table 5.3 Antihemorrhagics, B02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

B02A Antifibrinolytics 0.0548 0.0213 0.0760 0.0475 0.0180 0.0655

B02A A Amino acids 0.0548 0.0213 0.0760 0.0475 0.0180 0.0655 B02A A02 Tranexamic acid 0.0548 0.0213 0.0760 0.0475 0.0180 0.0655

B02B Vitamin K and other 0.0083 0.0052 0.0135 0.0065 0.0048 0.0113 hemostatics

B02B A Vitamin K 0.0074 0.0047 0.0121 0.0061 0.0043 0.0103 B02B A01 Phytomenadione 0.0074 0.0018 0.0092 0.0061 0.0017 0.0077 B02B A02 Menadione - 0.0029 0.0029 - 0.0026 0.0026

B02B X Other systemic hemostatics 0.0009 0.0005 0.0014 0.0004 0.0006 0.0010 B02B X05 Eltrombopag 0.0009 0.0005 0.0014 0.0004 0.0006 0.0010

Table 5.4 Antianemic preparations, B03 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

B03A Iron preparations 3.4650 0.0778 3.5428 3.1380 0.0820 3.2200

B03A A Iron bivalent, oral preparations 3.4457 0.0580 3.5037 3.1094 0.0603 3.1698 B03A A02 Ferrous fumarate 3.4457 0.0575 3.5033 3.1094 0.0603 3.1698 B03A A07 Ferrous sulfate - 0.0005 0.0005 - - -

B03A B Iron trivalent, oral preparations 0.0078 0.0180 0.0257 0.0142 0.0195 0.0337 B03A B01 Ferric sodium citrate - 0.0018 0.0018 - 0.0018 0.0018 B03A B05 Ferric oxide polymaltose 0.0078 0.0162 0.0240 0.0142 0.0176 0.0319 complexes

B03A C Iron, parenteral preparations 0.0115 0.0018 0.0133 0.0143 0.0022 0.0166

B03B Vitamin B12 and folic acid 10.1733 2.7402 12.9135 9.2431 2.8867 12.1298

B03B A Vitamin B12 (cyanocobalamin 0.3502 1.1183 1.4685 1.0620 1.4230 2.4850 and analogues) B03B A01 Cyanocobalamin 0.0939 0.3952 0.4891 0.1038 0.7643 0.8682 B03B A05 Mecobalamin 0.2563 0.7231 0.9794 0.9582 0.6586 1.6168

B03B B Folic acid and derivatives 9.8231 1.6219 11.4450 8.1811 1.4638 9.6448 B03B B01 Folic acid 9.8231 1.6219 11.4450 8.1811 1.4638 9.6448

B03X Other antianemic preparations 0.1410 0.4238 0.5648 0.2150 0.4663 0.6813

B03X A Other antianemic preparations 0.1410 0.4238 0.5648 0.2150 0.4663 0.6813 B03X A01 Erythropoietin 0.1353 0.3795 0.5147 0.2092 0.4234 0.6325 B03X A02 Darbepoetin alfa - 0.0010 0.0010 - 0.0012 0.0012 B03X A03 Methoxy polyethylene glycol- 0.0057 0.0434 0.0491 0.0058 0.0418 0.0476 epoetin beta

6 Cardiovascular System

Statistics on medicines for cardiovascular system 6.1

Table 6.1 Statistics by therapeutic subgroups for cardiovascular system, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

C Cardiovascular system 156.6089 34.7555 191.3644 163.5341 34.7823 198.3164

C01 Cardiac therapy 3.4602 1.2999 4.7601 3.4076 1.3260 4.7337 C02 Antihypertensives 2.3031 0.2651 2.5683 2.3668 0.2655 2.6323 C03 Diuretics 16.5607 2.0216 18.5823 14.9246 1.9595 16.8841 C04 Peripheral vasodilators 0.0236 0.0098 0.0334 0.0203 0.0136 0.0339 C07 Beta blocking agents 16.3077 3.7472 20.0549 14.2129 3.5064 17.7193 C08 Calcium channel blockers 59.8844 7.8863 67.7707 61.5062 7.5324 69.0386 C09 Agents acting on the renin- 31.3996 10.8191 42.2187 39.3969 11.2788 50.6757 angiotensin system C10 Lipid modifying agents 26.6695 8.7064 35.3759 27.6987 8.9001 36.5988

Table 6.2 Drugs for cardiac therapy, C01 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C01A Cardiac glycosides 0.2823 0.1280 0.4103 0.2317 0.1174 0.3490

C01A A Digitalis glycosides 0.2823 0.1280 0.4103 0.2317 0.1174 0.3490 C01A A05 Digoxin 0.2823 0.1280 0.4103 0.2317 0.1174 0.3490

C01B Antiarrhythmics, class I and III 0.0360 0.0635 0.0994 0.0349 0.0727 0.1076

C01B B Antiarrhythmics, class Ib 0.0015 0.0013 0.0028 0.0013 0.0014 0.0028 C01B B01 Lidocaine 0.0015 0.0013 0.0028 0.0013 0.0014 0.0028

C01B C Antiarrhythmics, class Ic 0.0025 0.0097 0.0121 0.0033 0.0103 0.0136 C01B C03 Propafenone 0.0002 0.0033 0.0035 - 0.0031 0.0031 C01B C04 Flecainide 0.0023 0.0064 0.0086 0.0033 0.0073 0.0106

C01B D Antiarrhythmics, class III 0.0320 0.0525 0.0845 0.0303 0.0610 0.0912 C01B D01 Amiodarone 0.0318 0.0506 0.0824 0.0301 0.0589 0.0891 C01B D07 Dronedarone 0.0002 0.0019 0.0021 0.0001 0.0020 0.0022

C01C Cardiac stimulants excluding 0.3132 0.0351 0.3483 0.3275 0.0382 0.3657 cardiac glycosides

C01C A Adrenergic and dopaminergic 0.3131 0.0351 0.3483 0.3274 0.0382 0.3656 agents C01C A02 Isoprenaline <0.0001 - <0.0001 <0.0001 - <0.0001 C01C A03 Norepinephrine 0.0689 0.0023 0.0712 0.0678 0.0028 0.0706 C01C A04 Dopamine 0.0096 0.0019 0.0114 0.0052 0.0018 0.0070 C01C A06 Phenylephrine 0.0033 - 0.0033 0.0049 - 0.0049 C01C A07 Dobutamine 0.0079 0.0004 0.0083 0.0066 0.0005 0.0071 C01C A24 Epinephrine 0.2134 0.0264 0.2398 0.2358 0.0295 0.2653 C01C A26 Ephedrine 0.0102 0.0041 0.0143 0.0071 0.0036 0.0107

C01C E Phosphodiesterase inhibitors 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 C01C E02 Milrinone 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001

C01D Vasodilators used in cardiac 1.3630 0.2734 1.6364 1.0840 0.2683 1.3523 diseases

C01D A Organic nitrates 1.3630 0.2734 1.6364 1.0840 0.2683 1.3523 C01D A02 Glyceryl trinitrate 0.2680 0.0385 0.3065 0.2384 0.0501 0.2885 C01D A08 Isosorbide dinitrate 0.7022 0.0235 0.7257 0.5685 0.0146 0.5831 C01D A14 Isosorbide mononitrate 0.3928 0.2114 0.6042 0.2771 0.2036 0.4807

C01E Other cardiac preparations 1.4657 0.7999 2.2656 1.7295 0.8295 2.5590

C01E A Prostaglandins 0.0002 <0.0001 0.0002 0.0002 <0.0001 0.0002 C01E A01 Alprostadil 0.0002 <0.0001 0.0002 0.0002 <0.0001 0.0002

C01E B Other cardiac preparations 1.4655 0.7999 2.2654 1.7293 0.8295 2.5588 C01E B10 Adenosine 0.0009 0.0002 0.0011 0.0010 0.0002 0.0012 C01E B15 Trimetazidine 1.4232 0.7033 2.1264 1.6997 0.7260 2.4256 C01E B17 Ivabradine 0.0415 0.0964 0.1378 0.0287 0.1021 0.1308 C01E B18 Ranolazine - - - - 0.0012 0.0012

Table 6.3 Antihypertensives, C02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C02A Antiadrenergic agents, 0.1742 0.1055 0.2796 0.1462 0.0952 0.2414 centrally acting

C02A B Methyldopa 0.1679 0.0163 0.1842 0.1401 0.0135 0.1536 C02A B01 Methyldopa (levorotatory) 0.1679 0.0163 0.1842 0.1401 0.0135 0.1536

C02A C Imidazoline receptor agonists 0.0062 0.0892 0.0955 0.0061 0.0817 0.0879 C02A C05 Moxonidine 0.0062 0.0892 0.0955 0.0061 0.0817 0.0879

C02C Antiadrenergic agents, 2.1234 0.1595 2.2829 2.2174 0.1700 2.3874 peripherally acting

C02C A Alpha-adrenoreceptor 2.1234 0.1595 2.2829 2.2174 0.1700 2.3874 antagonists C02C A01 Prazosin 1.8814 0.0335 1.9149 1.7354 0.0263 1.7618 C02C A04 Doxazosin 0.2420 0.1260 0.3680 0.4820 0.1436 0.6256

C02D Arteriolar smooth muscle, 0.0054 0.0001 0.0055 0.0032 0.0003 0.0034 agents acting on

C02D B Hydrazinophthalazine 0.0017 0.0001 0.0017 0.0020 0.0001 0.0021 derivatives C02D B02 Hydralazine 0.0017 0.0001 0.0017 0.0020 0.0001 0.0021

C02D C Pyrimidine derivatives 0.0037 0.0001 0.0038 0.0012 0.0002 0.0014 C02D C01 Minoxidil 0.0037 0.0001 0.0038 0.0012 0.0002 0.0014

C02D D Nitroferricyanide derivatives <0.0001 - <0.0001 - - - C02D D01 Nitroprusside <0.0001 - <0.0001 - - -

C02K Other antihypertensives 0.0002 0.0001 0.0003 <0.0001 0.0001 0.0001

C02K X Antihypertensives for 0.0002 0.0001 0.0003 <0.0001 0.0001 0.0001 pulmonary arterial hypertension C02K X01 Bosentan 0.0002 0.0001 0.0003 <0.0001 - <0.0001 C02K X05 Riociguat - <0.0001 <0.0001 - 0.0001 0.0001

Table 6.4 Diuretics, C03 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C03A Low-ceiling diuretics, thiazides 10.5427 0.6105 11.1532 9.7083 0.6339 10.3421

C03A A Thiazides, plain 10.5427 0.6105 11.1532 9.7083 0.6339 10.3421 C03A A03 Hydrochlorothiazide 10.5393 0.6105 11.1499 9.7083 0.6339 10.3421 C03A A04 Chlorothiazide 0.0033 - 0.0033 - - -

C03B Low-ceiling diuretics, 0.0447 0.4180 0.4627 0.0238 0.3616 0.3854 excluding thiazides

C03B A Sulfonamides, plain 0.0447 0.4154 0.4602 0.0238 0.3605 0.3843 C03B A04 Chlortalidone - 0.0002 0.0002 - 0.0076 0.0076 C03B A08 Metolazone 0.0114 - 0.0114 - - - C03B A11 Indapamide 0.0333 0.4153 0.4486 0.0238 0.3529 0.3767

C03B D Xanthine derivatives - 0.0026 0.0026 - 0.0011 0.0011 C03B D01 Theobromine - 0.0026 0.0026 - 0.0011 0.0011

C03C High-ceiling diuretics 5.0747 0.4907 5.5654 4.4278 0.6180 5.0458

C03C A Sulfonamides, plain 5.0747 0.4907 5.5654 4.4278 0.6180 5.0458 C03C A01 Furosemide 5.0400 0.4685 5.5085 4.3935 0.5820 4.9755 C03C A02 Bumetanide 0.0348 0.0222 0.0569 0.0343 0.0360 0.0703

C03D Potassium-sparing agents 0.3002 0.1305 0.4307 0.2772 0.1279 0.4050

C03D A Aldosterone antagonists 0.3002 0.1305 0.4307 0.2772 0.1279 0.4050 C03D A01 Spironolactone 0.2999 0.1269 0.4268 0.2772 0.1230 0.4001 C03D A04 Eplerenone 0.0003 0.0037 0.0039 <0.0001 0.0049 0.0049

C03E Diuretics and potassium- 0.5983 0.3719 0.9702 0.4876 0.2181 0.7057 sparing agents in combination

C03E A Low-ceiling diuretics and 0.5983 0.3719 0.9702 0.4876 0.2181 0.7057 potassium-sparing agents C03E A01 Hydrochlorothiazide and 0.5983 0.3719 0.9702 0.4876 0.2181 0.7057 potassium-sparing agents

Table 6.5 Peripheral vasodilators, C04 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C04A Peripheral vasodilators 0.0236 0.0098 0.0334 0.0203 0.0136 0.0339

C04A D Purine derivatives 0.0214 0.0096 0.0310 0.0189 0.0136 0.0325 C04A D03 Pentoxifylline 0.0214 0.0096 0.0310 0.0189 0.0136 0.0325

C04A E Ergot alkaloids 0.0022 0.0002 0.0025 0.0014 - 0.0014 C04A E01 Ergoloid mesylates 0.0022 0.0002 0.0025 0.0014 - 0.0014

Table 6.6 Beta blocking agents, C07 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C07A Beta blocking agents 16.3077 3.4001 19.7078 14.2129 3.2270 17.4399

C07A A Beta blocking agents, 0.2289 0.1495 0.3783 0.2122 0.1257 0.3379 non-selective C07A A05 Propranolol 0.2257 0.1372 0.3629 0.2104 0.1145 0.3249 C07A A07 Sotalol 0.0032 0.0123 0.0155 0.0018 0.0112 0.0130

C07A B Beta blocking agents, 15.8593 3.1297 18.9890 13.7833 2.9971 16.7803 selective C07A B02 Metoprolol 8.1411 0.2942 8.4353 6.6570 0.2888 6.9458 C07A B03 Atenolol 6.8768 2.0422 8.9190 5.7586 1.8108 7.5694 C07A B05 Betaxolol - 0.0342 0.0342 - 0.0261 0.0261 C07A B07 Bisoprolol 0.8415 0.6712 1.5127 1.3677 0.7246 2.0923 C07A B09 Esmolol <0.0001 - <0.0001 <0.0001 <0.0001 <0.0001 C07A B12 Nebivolol - 0.0879 0.0879 - 0.1468 0.1468

C07A G Alpha and beta blocking 0.2196 0.1209 0.3405 0.2174 0.1042 0.3217 agents C07A G01 Labetalol 0.0653 0.0124 0.0777 0.0671 0.0120 0.0791 C07A G02 Carvedilol 0.1543 0.1085 0.2628 0.1503 0.0922 0.2426

C07B Beta blocking agents and - 0.0493 0.0493 - 0.0488 0.0488 thiazides

C07B B Beta blocking agents, - 0.0493 0.0493 - 0.0488 0.0488 selective, and thiazides C07B B07 Bisoprolol and thiazides - 0.0493 0.0493 - 0.0488 0.0488

C07C Beta blocking agents and - 0.2977 0.2977 - 0.2306 0.2306 other diuretics

C07C B Beta blocking agents, - 0.2977 0.2977 - 0.2306 0.2306 selective, and other diuretics C07C B03 Atenolol and other diuretics - 0.2977 0.2977 - 0.2306 0.2306

Table 6.7 Calcium channel blockers, C08 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C08C Selective calcium channel 59.6225 7.7807 67.4032 61.2607 7.3982 68.6589 blockers with mainly vascular effects

C08C A Dihydropyridine derivatives 59.6225 7.7807 67.4032 61.2607 7.3982 68.6589 C08C A01 Amlodipine 54.6063 6.9215 61.5278 56.8378 6.5670 63.4048 C08C A02 Felodipine 3.1879 0.2795 3.4674 3.4149 0.2913 3.7063 C08C A04 Nicardipine <0.0001 - <0.0001 <0.0001 - <0.0001 C08C A05 Nifedipine 1.8276 0.4442 2.2719 1.0073 0.4130 1.4203 C08C A06 Nimodipine 0.0007 0.0002 0.0009 0.0006 0.0002 0.0007 C08C A09 Lacidipine - 0.0074 0.0074 - 0.0056 0.0056 C08C A13 Lercanidipine - 0.1279 0.1279 - 0.1210 0.1210

C08D Selective calcium channel 0.2619 0.1056 0.3675 0.2455 0.1199 0.3654 blockers with direct cardiac effects

C08D A Phenylalkylamine derivatives 0.0437 0.0303 0.0740 0.0389 0.0280 0.0669 C08D A01 Verapamil 0.0437 0.0303 0.0740 0.0389 0.0280 0.0669

C08D B Benzothiazepine derivatives 0.2182 0.0753 0.2935 0.2066 0.0919 0.2985 C08D B01 Diltiazem 0.2182 0.0753 0.2935 0.2066 0.0919 0.2985

C08G Calcium channel blockers - - - - 0.0143 0.0143 and diuretics

C08G A Calcium channel blockers - - - - 0.0143 0.0143 and diuretics C08G A02 Amlodipine and diuretics - - - - 0.0143 0.0143

Table 6.8 Agents acting on the renin-angiotensin system, C09 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C09A ACE inhibitors, plain 26.9887 2.5648 29.5535 33.9215 2.6713 36.5927

C09A A ACE inhibitors, plain 26.9887 2.5648 29.5535 33.9215 2.6713 36.5927 C09A A01 Captopril 1.4110 0.0088 1.4198 0.8929 0.0672 0.9601 C09A A02 Enalapril 3.5275 0.5672 4.0947 4.3446 0.5258 4.8705 C09A A03 Lisinopril 0.0446 0.2905 0.3352 0.0283 0.3075 0.3357 C09A A04 Perindopril 21.7401 1.4823 23.2224 28.4049 1.5762 29.9811 C09A A05 Ramipril 0.2606 0.2001 0.4607 0.2429 0.1759 0.4188 C09A A16 Imidapril 0.0049 0.0159 0.0208 0.0078 0.0187 0.0265

C09B ACE inhibitors, combinations 0.2591 0.5814 0.8404 0.2548 0.6487 0.9035

C09B A ACE inhibitors and diuretics 0.2591 0.1521 0.4111 0.2548 0.1568 0.4116 C09B A04 Perindopril and diuretics 0.2591 0.1521 0.4111 0.2548 0.1568 0.4116

C09B B ACE inhibitors and calcium - 0.4293 0.4293 - 0.4771 0.4771 channel blockers C09B B04 Perindopril and amlodipine - 0.4293 0.4293 - 0.4771 0.4771

C09B X ACE inhibitors, other - - - - 0.0149 0.0149 combinations C09B X01 Perindopril, amlodipine and - - - - 0.0149 0.0149 indapamide

Table 6.8 (continued) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C09C Angiotensin II antagonists, 3.3501 3.7777 7.1278 4.3864 3.8338 8.2202 plain

C09C A Angiotensin II antagonists, 3.3501 3.7777 7.1278 4.3864 3.8338 8.2202 plain C09C A01 Losartan 0.9182 1.1337 2.0518 1.6740 1.1167 2.7907 C09C A03 Valsartan 0.3476 0.5464 0.8939 0.5639 0.5332 1.0971 C09C A04 Irbesartan 0.7730 0.5326 1.3056 1.0549 0.5802 1.6351 C09C A06 Candesartan 0.0010 0.4025 0.4035 0.0005 0.3892 0.3897 C09C A07 Telmisartan 1.3104 0.8953 2.2057 1.0932 0.9527 2.0458 C09C A08 Olmesartan medoxomil - 0.2674 0.2674 - 0.2618 0.2618

C09D Angiotensin II antagonists, 0.8018 3.8800 4.6817 0.8342 4.1111 4.9453 combinations

C09D A Angiotensin II antagonists and 0.4277 1.7976 2.2253 0.4451 1.8089 2.2540 diuretics C09D A01 Losartan and diuretics 0.1756 0.5533 0.7289 0.1209 0.6035 0.7244 C09D A03 Valsartan and diuretics 0.0765 0.4703 0.5468 0.1035 0.4341 0.5376 C09D A04 Irbesartan and diuretics 0.0526 0.2963 0.3489 0.1489 0.3110 0.4599 C09D A06 Candesartan and diuretics 0.0002 0.1352 0.1354 0.0001 0.1279 0.1279 C09D A07 Telmisartan and diuretics 0.1228 0.2932 0.4160 0.0717 0.2859 0.3576 C09D A08 Olmesartan medoxomil and - 0.0493 0.0493 - 0.0465 0.0465 diuretics

C09D B Angiotensin II antagonists and 0.3619 1.8388 2.2007 0.3796 2.0394 2.4190 calcium channel blockers C09D B01 Valsartan and amlodipine 0.0835 1.0032 1.0867 0.1129 1.0379 1.1508 C09D B02 Olmesartan medoxomil and - 0.1499 0.1499 - 0.1831 0.1831 amlodipine C09D B04 Telmisartan and amlodipine 0.2677 0.4800 0.7478 0.2539 0.5873 0.8412 C09D B06 Losartan and amlodipine 0.0107 0.2056 0.2163 0.0128 0.2310 0.2438

C09D X Angiotensin II antagonists, 0.0122 0.2436 0.2558 0.0095 0.2628 0.2723 other combinations C09D X01 Valsartan, amlodipine and 0.0122 0.2436 0.2558 0.0094 0.2536 0.2630 hydrochlorothiazide C09D X04 Valsartan and sacubitril - <0.0001 <0.0001 0.0001 0.0092 0.0093

C09X Other agents acting on the - 0.0152 0.0152 - 0.0140 0.0140 renin-angiotensin system

C09X A Renin-inhibitors - 0.0152 0.0152 - 0.0140 0.0140 C09X A02 Aliskiren - 0.0152 0.0152 - 0.0140 0.0140

Table 6.9 Lipid modifying agents, C10 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

C10A Lipid modifying agents, plain 26.5762 8.2571 34.8332 27.6177 8.4235 36.0412

C10A A HMG CoA reductase inhibitors 25.4154 7.6270 33.0424 26.6385 7.7476 34.3861 C10A A01 Simvastatin 21.4087 2.4403 23.8490 20.0099 2.2834 22.2933 C10A A02 Lovastatin 0.1203 0.1018 0.2220 0.1177 0.0708 0.1885 C10A A03 Pravastatin 0.0952 0.0208 0.1160 0.0804 0.0181 0.0985 C10A A04 Fluvastatin - 0.0160 0.0160 - 0.0113 0.0113 C10A A05 Atorvastatin 3.6784 3.2641 6.9425 6.2988 3.3942 9.6930 C10A A07 Rosuvastatin 0.1129 1.7839 1.8968 0.1318 1.9697 2.1015

C10A B Fibrates 0.9462 0.5247 1.4709 0.7521 0.5447 1.2968 C10A B04 Gemfibrozil 0.7341 0.0142 0.7484 0.5680 0.0170 0.5850 C10A B05 Fenofibrate 0.2114 0.4959 0.7073 0.1837 0.5118 0.6955 C10A B08 Ciprofibrate 0.0007 0.0145 0.0153 0.0005 0.0158 0.0163

C10A C Bile acid sequestrants 0.0001 - 0.0001 0.0002 - 0.0002 C10A C01 Colestyramine 0.0001 - 0.0001 0.0002 - 0.0002

C10A X Other lipid modifying agents 0.2144 0.1054 0.3198 0.2269 0.1312 0.3581 C10A X09 Ezetimibe 0.2144 0.1054 0.3198 0.2269 0.1312 0.3581

C10B Lipid modifying agents, 0.0933 0.4494 0.5427 0.0810 0.4766 0.5576 combinations

C10B A HMG CoA reductase inhibitors 0.0454 0.2730 0.3184 0.0536 0.2980 0.3516 in combination with other lipid modifying agents C10B A02 Simvastatin and ezetimibe 0.0454 0.2730 0.3184 0.0536 0.2979 0.3514 C10B A03 Pravastatin and fenofibrate - - - - 0.0002 0.0002

C10B X HMG CoA reductase inhibitors, 0.0479 0.1764 0.2244 0.0274 0.1786 0.2060 other combinations C10B X03 Atorvastatin and amlodipine 0.0479 0.1764 0.2244 0.0274 0.1786 0.2060

Utilisation of drugs for cardiovascular disorders 6.2 Omar Ismail, Amin Ariff Nuruddin, Abd Kahar Abd Ghapar, Jivanraj Nagarajah

Drugs used in management of cardiovascular disease (CVD) remain the most frequently prescribed in Malaysia (amlodipine with DDD of 61.5278 in 2015 and 63.4048 in 2016), partly due to the rising prevalence of cardiovascular risk factors and improved access of patients with CVD to healthcare facilities.1 The value presented in this chapter is based on DDD/1,000 inhabitants/day.

Listed in Table 5.2 are the statistics for antithrombotic agents. Overall, from 2015 to 2016, there was a slight increase in the use of antithrombotic agents (from 14.3480 to 14.8307, but drastic changes from usage in 2011, which was 9.7833). These changes were seen both in public and private sector.

Among the antithrombotic agents, the standard oral anticoagulant, warfarin usage showed slight decrease in total usage especially in private sector (from 0.4918 in 2011 to 0.5239 in 2014 to 0.3472 in 2015 to 0.3443 in 2016), probably due to introduction and increase usage of direct oral anticoagulant, DOAC (0.0190 in 2011 to 0.1270 in 2014 to 0.2236 in 2016). Usage of DOACs may vary from public to private sector showing an increase use in the private sector. It may reflect easiness of administration without strict monitoring of coagulation profile with better safety and effectiveness of DOACs compared to warfarin despite its higher cost.2,3

The use of heparin based anticoagulants however remains almost the same (0.5549 in 2015 and 0.5496 in 2016). Similar trend was also noted in the other antithrombotic agents (fondaparinux) from 0.0250 in 2015 to 0.0291 in 2016 which was similar to usage in 2014.

Platelet aggregation inhibitors showed a consistent increase from 13.2315 in 2015 to 13.6835 in 2016. Acetylsalicylic acid (aspirin) remained the most widely used agent (10.6650 in 2015 and 10.8170 in 2016) constituting more than 70% of the total use of all antithrombotic agents, followed by clopidogrel (14% of total antithrombotic agents, 1.9491 in 2015 and 2.1301 in 2016) and ticlopidine (3.5% in 2016, 0.4183 in 2015 and 0.5225 in 2016). There was also slight increase in newer agent, ticagrelor (0.0692 in 2014 to 0.0861 in 2015 and 0.1046 in 2016). The increase in ticagrelor use reflects the change of practice in management of acute coronary syndrome.4 The use of other platelet aggregation inhibitors remains low for the past six years.

Among thrombolytics/fibrinolytics drugs, although the most commonly used was streptokinase in the public sector due to the cost factor, the use has reduced from 0.0010 in 2015 to 0.0008 in 2016 partly due to introduction of primary percutaneous coronary intervention (PCI) strategy for ST-elevation myocardial infarction which is preferred over thrombolytics, especially in private sector as well as public health institution.4,5,6 Similar changes were also observed in the other types of thrombolytic agents used.

Table 6.2 refers to usage of other cardiac stimulants. Usage of digoxin in Malaysia is low (0.4103 in 2015 and 0.3490 in 2016) compared to European countries, i.e. Finland (2.66 in 2016).7 This may be due in part to the increasing number of heart failure patients receiving evidence-based selective beta blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), and also undergoing cardiac resynchronization therapy.8 In addition, some patients with atrial fibrillation where digoxin was previously used for rate control, may have been referred for curative therapy, i.e. radio- selective ablation.

Other commonly prescribed anti-arrhythmic drugs were amiodarone followed by flecainide. Amiodarone utilisation remained unchanged with 0.0824 in 2015 and 0.0891 in 2016, while the use of flecainide was 0.0086 in 2015 and 0.0106 in 2016, which was lower compared to the usage in European countries (DDD of Finland in 2016 was 0.49 with amiodarone and 1.42 with flecainide).7 The consumption of both drugs were mainly at the private compared to the public sector.

Cardiac stimulants beside cardiac glycosides that were commonly used especially in the intensive care settings were epinephrine (0.2398 in 2015 and 0.2653 in 2016), followed by norepinephrine (0.0712 in 2015 and 0.0706 in 2016) and dopamine (0.0114 in 2015 and 0.0070 in 2016).

The main vasodilators used as anti-ischaemic pharmacotherapy were nitrates (1.6364 in 2015 and 1.3523 in 2016). However, it was superseded by trimetazidine (2.1264 in 2015 and 2.4256 in 2016). The use of newer agents such as ivabradine was still low (0.1378 in 2015 and 0.1308 in 2016). Another newer agent for refractory angina (ranolazine) was only started in practice in 2016 (0.0012 in 2016).

The other main vasodilators (ACE inhibitors, ARBs and selective beta blockers) are also used for heart failure and stable coronary artery disease.

Utilisation of drugs for hypertension 6.3 Azhari Rosman, Wardati Mazlan Kepli

Non-communicable diseases (NCDs) are already the main cause of death in Malaysia and the biggest contributors in terms of disability-adjusted life years (DALYs), with hypertension the biggest contributor for both males and females.9 The latest National Health and Morbidity Survey (NHMS) for NCD risk factors in 2015 showed an overall prevalence of hypertension of 30.3% among adults aged 18 years and above.9 Hypertension is also a common risk factor for CVD, such as heart failure and ischaemic heart disease.4,10

Medicines listed in Table 6.3 to 6.8 are categorized as antihypertensives, diuretics, peripheral vasodilators, beta blocking agents, calcium channel blockers and agents acting on the renin-angiotensin systems (ACE inhibitors and angiotensin II antagonists). These agents are not only indicated for the treatment of hypertension,11 but also for the treatment of heart failure12 and stable coronary artery disease.13

The highest usage of antihypertensive classes for 2015 and 2016 were dihydropyridine derivatives (67.4032 to 68.6589 DDD/1,000 inhabitants/day), ACE Inhibitors (29.5535 to 36.5927 DDD/1,000 inhabitants/day), beta-blocking agents (19.7078 to 17.4399 DDD/1,000 inhabitants/day), thiazides (11.1532 to 10.3421 DDD/1,000 inhabitants/day) and angiotensin II antagonists (7.1278 to 8.2202 DDD/1,000 inhabitants/day). From 2015 to 2016, a notable increase was observed for ACE inhibitors and angiotensin II antagonists or ARBs, approximately 24% and 15%, respectively.

The first eight amongst the top 10 single antihypertensive agents used were similar in 2015 and 2016 following the sequence of amlodipine, perindopril, hydrochlorothiazide, atenolol, metoprolol, frusemide, enalapril and felodipine. There was a shift in consumption for the last two items, notably nifedipine and telmisartan in 2015 to losartan and bisoprolol in 2016. This change could be attributed to change in availability of generic formulation of latter and wider prescriber category.

In between 2015 and 2016, the top 10 drugs for hypertensive with more than 25% increment were chlortalidone, nebivolol, bisoprolol, doxazosin, losartan, combination of irbesartan and diuretics, perindopril, imidapril, eplerenone and lastly, irbesartan.

Utilisation of lipid modifying drugs 6.4 Wan Azman Wan Ahmad, Nirmala Jagan

Cardiovascular disease remains the leading cause of death over the past decade. In 2017, the percentage of death caused by ischaemic heart disease was 13.9%.14 One of the risk factors for CVD is hypercholestrolaemia. Lowering plasma cholesterol level had been shown to reducing risk of CVD. The prevalence of hypercholesterolaemia in Malaysian adults was 47.7% (known and undiagnosed), as reported by NHMS 2015.1 There was a general increasing trend in the prevalence of hypercholesterolaemia with age from 22.0% in the 18 to 19-year-old age group, reaching a peak of 68.8% in 55 to 59-year-old age group.

Latest clinical practice guideline on management of dyslipidaemia in 2018 had recommended the use of high-intensity statins in high risk and very high risk patients.15 The target low density lipoprotein cholesterol (LDL-c) level for these patients has been lowered to less than 1.8mmol/L or 50% reduction from baseline LDL-c level.

Overall, there was an increasing trend in the use of lipid modifying agents in 2015 to 2016, which was more significant in the public sector. There was a marked increase in utilisation of β-hydroxy β-methylglutaryl- coenzyme A (HMG CoA) reductase inhibitors, also known as statins in the year 2015 to 2016 up to 70% more compared to 2013 and 2014 cohort. Overall, the fibrate use was in reducing trend, particularly in the public sector. The use of statins with other combinations has increased in 2015 and 2016 compared to the 2013 and 2014 cohort. It was mainly contributed by the use in the public sector, which was not recorded in the earlier cohort.

In Malaysia, statins used consists of simvastatin (65%), atorvastatin (28%) and rosuvastatin (6%) and other statins (1%). The utilisation of high-intensity statins (atorvastatin and rosuvastatin) has generally increased in 2015 and 2016 cohort compared to the earlier cohort, which could be attributed to the availability of the generic formulations and in concordance with the national guideline recommendations. A dramatic drop in the use of lovastatin was noted in the present cohort, implying a deprescribing pattern.16 The use of pravastatin was constant but the use of fluvastatin was minimal and decreasing. The increase in simvastatin use could be attributed to the absence of lovastatin in public sector and the former being the first line agent for stable coronary artery disease patients and those requiring primary prevention therapy. In private sector, the use of simvastatin was the same over the years compared to previous cohort. However, the use of simvastatin in public sector has markedly increased up to 65% in 2015 and 2016 cohort compared to 2013 and 2014 cohort.

Overall there was a decreasing trend in gemfibrozil use, especially in public sector but it remains the same in private sector. The overall use of fenofibrate has increased, notably a four-fold increase in public sector but it was similar in the private sector.

The use of ciprofibrate was mainly in the private sector with a decreasing trend in public sector. There was a minimal use of bile acid sequestrants. The overall use of ezetimibe was increasing in trend both in

public and private sector. The combination of simvastatin and ezetimibe has remained the same for the 2015 and 2016 cohort in both public and private sector.

Overall, there was an increase in use of the combination of atorvastatin and amlodipine in public sector compared to year 2014 which may be due to the availability of the agent but the used was the same in the private sector.

Ninety-six percent of lipid modifying agents used in Malaysia was statins, which was similar to Finland Statistics of Medicines report 2015.17 In Australia, atorvastatin was the most used statin followed by rosuvastatin18 whereas in Malaysia, simvastatin was the most commonly used statin which may be attributed to availability and cost.

REFERENCES

1. Volume II: Non-Communicable Disease, Risk Factors and Other Health Problems. National Health and Morbidity Survey 2015; National Institutes of Health, Ministry of Health Malaysia: Kuala Lumpur, 2015. 2. Yao, X.; Abraham, N. S.; Sangaralingham, L. R.; et al. Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban versus Warfarin in Nonvalvular Atrial Fibrillation. Journal of the American Heart Association 2016, 5, e003725. 3. Hernandez, I.; Zhang, Y.; Brooks, M.; et al. Anticoagulation Use and Clinical Outcomes after Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation. Stroke 2017, 48(1), 159-166. 4. W.A. Wan Ahmad (Ed). Annual Report of the NCVD-ACS Registry, 2014-2015; National Heart Association of Malaysia, Ministry of Health Malaysia: Kuala Lumpur, 2017. 5. W.A. Wan Ahmad (Ed). Annual Report of the NCVD-PCI Registry, 2015-2016; National Heart Association of Malaysia, Ministry of Health Malaysia: Kuala Lumpur, 2018. 6. Management of Acute ST Segment Elevation Myocardial Infraction (STEMI): Clinical Practice Guideline 2014 3rd edition; National Heart Association of Malaysia, Ministry of Health Malaysia: Kuala Lumpur, 2014. 7. Finnish Statistics on Medicines 2016; Finnish Medicines Agency and Social Insurance Institution: Helsinki, 2017. 8. Management of Heart Failure: Clinical Practice Guideline 2014 3rd edition; National Heart Association of Malaysia, Ministry of Health Malaysia: Kuala Lumpur, 2014. 9. Volume II: Non-Communicable Disease, Risk Factors and Other Health Problems. National Health and Morbidity Survey 2015; National Institutes of Health, Ministry of Health Malaysia: Kuala Lumpur, 2015. 10. Reyes, E. B.; Ha, J. W.; Firdaus, I.; et al. Heart Failure across Asia: Same Healthcare Burden but Differences in Organization of Care. Int. J. Cardiol. 2016, 223, 163-167. 11. Clinical Practice Guidelines Management of Hypertension 5th Edition; Malaysian Society of Hypertension: Kuala Lumpur, 2018. 12. Clinical Practice Guidelines Management of Heart Failure 2019 4th Edition; National Heart Association of Malaysia: Kuala Lumpur, 2019. 13. Clinical Practice Guidelines of Stable Coronary Artery Disease 2018 2nd Edition; National Heart Association of Malaysia: Kuala Lumpur, 2018. 14. Statistics on Causes of Death Malaysia 2018; Department of Statistics Malaysia: Kuala Lumpur, 2018. 15. 5th Edition of Clinical Practice Guidelines: Management of Dylipidemia 2017; Ministry of Health Malaysia: Putrajaya, 2017. 16. Azuana, R.; Syed, M. A.; Saperi, S.; Faridah, A. M. Y. National Drug Formulary Review of Statin Therapeutic Group using the Multi-attribute Scoring Tool. Therapeutics and Clinical Risk Management 2013, 9, 491-504. 17. Finnish Statistics on Medicines 2015; Finnish Medicines Agency and Social Insurance Institution: Helsinki, 2016. 18. Australian Statistics on Medicines 2015; Pharmaceutical Benefit Scheme, Department of Health: Canberra, 2016. http://www.pbs.gov.au/info/statistics/asm/asm-2015.

7 Dermatologicals

Statistics on dermatological preparations 7.1

Table 7.1 Statistics by therapeutic groups for dermatological preparations, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

D Dermatologicals 6.1556 25.7681 31.9237 5.2952 25.4566 30.7518

D01 Antifungals for dermatological 1.3972 8.4211 9.8183 1.1965 7.7822 8.9787 use D05 Antipsoriatics 0.5463 2.0592 2.6056 0.3115 2.1572 2.4687 D06 Antibiotics and 1.2411 1.5938 2.8349 1.1633 1.6163 2.7796 chemotherapeutics for dermatological use D07 Corticosteroids, dermatological 2.8156 8.5429 11.3586 2.5007 8.5708 11.0715 preparations D10 Anti-acne preparations 0.1252 1.7448 1.8700 0.0848 1.8418 1.9266 D11 Other dermatological 0.0302 3.4062 3.4364 0.0383 3.4883 3.5266 preparations

Table 7.2 Antifungal for dermatological use, D01 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

D01A Antifungals for topical use 1.3330 7.9283 9.2614 1.1457 7.2710 8.4167

D01A A Antibiotics 0.0705 0.0211 0.0917 0.0519 0.0200 0.0719 D01A A01 Nystatin 0.0705 0.0211 0.0917 0.0519 0.0200 0.0719

D01A C Imidazole and triazole 1.0021 7.1474 8.1495 0.9299 6.8433 7.7732 derivatives D01A C01 Clotrimazole 0.1251 0.8797 1.0048 0.0954 0.9569 1.0523 D01A C02 Miconazole 0.7112 0.6932 1.4043 0.7368 0.5842 1.3209 D01A C03 Econazole - - - - 0.0003 0.0003 D01A C05 Isoconazole - 0.0067 0.0067 - 0.0068 0.0068 D01A C08 Ketoconazole 0.1642 1.4993 1.6635 0.0925 1.3479 1.4404 D01A C14 Sertaconazole - 0.1091 0.1091 - 0.1294 0.1294 D01A C20 Imidazoles/triazoles in 0.0016 3.9594 3.9610 0.0052 3.8180 3.8232 combination with corticosteroids

D01A E Other antifungals for topical 0.2604 0.7598 1.0202 0.1639 0.4077 0.5716 use D01A E12 Salicylic acid 0.1269 0.0223 0.1492 0.0761 0.0380 0.1141 D01A E13 Selenium sulfide 0.1328 0.0286 0.1613 0.0876 0.0139 0.1015 D01A E14 Ciclopirox - 0.0748 0.0748 - - - D01A E15 Terbinafine - 0.0995 0.0995 - 0.0833 0.0833 D01A E16 Amorolfine 0.0007 0.0011 0.0018 0.0002 0.0010 0.0012 D01A E18 Tolnaftate - 0.1397 0.1397 - 0.1506 0.1506 D01A E20 Other antifungals for topical - 0.3866 0.3866 - 0.1146 0.1146 use, combinations D01A E22 Naftifine - 0.0073 0.0073 - 0.0063 0.0063

D01B Antifungals for systemic use 0.0641 0.4928 0.5569 0.0508 0.5112 0.5620

D01B A Antifungals for systemic use 0.0641 0.4928 0.5569 0.0508 0.5112 0.5620 D01B A01 Griseofulvin 0.0577 0.4875 0.5453 0.0479 0.5017 0.5496 D01B A02 Terbinafine 0.0064 0.0052 0.0116 0.0029 0.0095 0.0124

Table 7.3 Antipsoriatics, D05 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

D05A Antipsoriatics for topical use 0.5386 2.0591 2.5977 0.3059 2.1568 2.4627

D05A A Tars 0.4669 2.0170 2.4839 0.2789 2.1233 2.4022

D05A X Other antipsoriatics for topical 0.0717 0.0421 0.1138 0.0270 0.0335 0.0605 use D05A X02 Calcipotriol 0.0086 0.0023 0.0109 0.0047 0.0036 0.0083 D05A X52 Calcipotriol, combinations 0.0630 0.0399 0.1029 0.0223 0.0299 0.0522

D05B Antipsoriatics for systemic use 0.0078 0.0001 0.0079 0.0057 0.0004 0.0061

D05B A Psoralens for systemic use 0.0001 - 0.0001 0.0003 - 0.0003 D05B A02 Methoxsalen 0.0001 - 0.0001 0.0003 - 0.0003

D05B B Retinoids for treatment of 0.0076 0.0001 0.0077 0.0054 0.0004 0.0058 psoriasis D05B B02 Acitretin 0.0076 0.0001 0.0077 0.0054 0.0004 0.0058

Table 7.4 Antibiotics and chemotherapeutics for dermatological use, D06 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

D06A Antibiotics for topical use 0.8727 1.3871 2.2597 0.8660 1.4141 2.2801

D06A X Other antibiotics for topical 0.8727 1.3871 2.2597 0.8660 1.4141 2.2801 use D06A X01 Fusidic acid 0.0403 0.7183 0.7586 0.0447 0.7974 0.8421 D06A X04 Neomycin 0.7578 0.2782 1.0360 0.7154 0.2450 0.9604 D06A X07 Gentamicin 0.0406 0.1549 0.1956 0.0206 0.1415 0.1621 D06A X09 Mupirocin 0.0339 0.2347 0.2687 0.0853 0.2299 0.3151 D06A X13 Retapamulin - 0.0009 0.0009 - 0.0004 0.0004

D06B Chemotherapeutics for topical 0.3685 0.2067 0.5752 0.2973 0.2022 0.4995 use

D06B A Sulfonamides 0.3656 0.1364 0.5019 0.2966 0.1279 0.4244 D06B A01 Silver sulfadiazine 0.3656 0.1364 0.5019 0.2966 0.1279 0.4244

D06B B Antivirals 0.0029 0.0564 0.0593 0.0007 0.0533 0.0541 D06B B03 Aciclovir 0.0027 0.0557 0.0584 0.0006 0.0525 0.0531 D06B B10 Imiquimod 0.0001 0.0007 0.0009 0.0001 0.0008 0.0009

D06B X Other chemotherapeutics - 0.0140 0.0140 - 0.0210 0.0210 D06B X01 Metronidazole - 0.0140 0.0140 - 0.0210 0.0210

Table 7.5 Corticosteroids, dermatological preparations, D07 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

D07A Corticosteroids, plain 2.7068 5.7006 8.4074 2.4420 5.6280 8.0701

D07A A Corticosteroids, weak 1.1128 1.0917 2.2045 0.9086 1.0742 1.9828 (group I) D07A A02 Hydrocortisone 1.1128 1.0917 2.2045 0.9086 1.0742 1.9828

D07A B Corticosteroids, moderately 0.0850 0.1489 0.2339 0.0710 0.1590 0.2300 potent (group II) D07A B01 Clobetasone 0.0850 0.0643 0.1493 0.0710 0.0658 0.1368 D07A B08 Desonide - 0.0782 0.0782 - 0.0907 0.0907 D07A B09 Triamcinolone - 0.0063 0.0063 - 0.0025 0.0025

D07A C Corticosteroids, potent 1.4229 2.2937 3.7166 1.4313 2.2508 3.6821 (group III) D07A C01 Betamethasone 1.3828 1.5445 2.9273 1.3932 1.4182 2.8114 D07A C04 Fluocinolone acetonide - 0.0110 0.0110 - 0.0158 0.0158 D07A C13 Mometasone 0.0402 0.6694 0.7096 0.0382 0.7320 0.7702 D07A C17 Fluticasone - 0.0688 0.0688 - 0.0847 0.0847

D07A D Corticosteroids, very potent 0.0860 2.1663 2.2523 0.0312 2.1441 2.1752 (group IV) D07A D01 Clobetasol 0.0860 2.1663 2.2523 0.0312 2.1441 2.1752

D07B Corticosteroids, combinations 0.0042 0.7808 0.7850 0.0146 0.8445 0.8591 with antiseptics

D07B C Corticosteroids, potent, 0.0042 0.7808 0.7850 0.0146 0.8445 0.8591 combinations with antiseptics D07B C01 Betamethasone and 0.0042 0.7808 0.7850 0.0146 0.8445 0.8591 antiseptics

Table 7.5 (continued) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

D07C Corticosteroids, combinations 0.1046 2.0582 2.1629 0.0441 2.0913 2.1354 with antibiotics

D07C A Corticosteroids, weak, 0.0208 0.0652 0.0861 0.0159 0.0782 0.0941 combinations with antibiotics D07C A01 Hydrocortisone and antibiotics 0.0208 0.0652 0.0861 0.0159 0.0782 0.0941

D07C C Corticosteroids, potent, 0.0838 1.9930 2.0768 0.0282 2.0132 2.0413 combinations with antibiotics D07C C01 Betamethasone and 0.0838 1.9918 2.0756 0.0282 2.0113 2.0394 antibiotics D07C C02 Fluocinolone acetonide and - 0.0012 0.0012 - 0.0019 0.0019 antibiotics

D07X Corticosteroids, other - 0.0033 0.0033 - 0.0069 0.0069 combinations

D07X A Corticosteroids, weak, other - 0.0033 0.0033 - 0.0069 0.0069 combinations D07X A01 Hydrocortisone, other - 0.0033 0.0033 - 0.0069 0.0069 combinations

Table 7.6 Anti-acne preparations, D10 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

D10A Anti-acne preparations for 0.1164 1.6754 1.7918 0.0792 1.7745 1.8538 topical use

D10A B Preparations containing sulfur - 0.1753 0.1753 - 0.1741 0.1741 D10A B02 Sulfur - 0.1753 0.1753 - 0.1741 0.1741

D10A D Retinoids for topical use in 0.0345 0.2670 0.3015 0.0284 0.2783 0.3068 acne D10A D01 Tretinoin 0.0219 0.0608 0.0827 0.0177 0.0560 0.0736 D10A D03 Adapalene 0.0126 0.1734 0.1861 0.0108 0.1926 0.2034 D10A D51 Tretinoin, combinations - 0.0093 0.0093 - 0.0070 0.0070 D10A D53 Adapalene, combinations - 0.0236 0.0236 - 0.0227 0.0227

D10A E Peroxides 0.0809 0.5867 0.6676 0.0499 0.6772 0.7272 D10A E01 Benzoyl peroxide 0.0809 0.5867 0.6676 0.0499 0.6772 0.7272

D10A F Antiinfectives for treatment of - 0.6302 0.6302 - 0.6262 0.6262 acne D10A F01 Clindamycin - 0.6117 0.6117 - 0.6103 0.6103 D10A F02 Erythromycin - 0.0001 0.0001 - - - D10A F51 Clindamycin, combinations - 0.0184 0.0184 - 0.0159 0.0159

D10A X Other anti-acne preparations 0.0011 0.0161 0.0172 0.0009 0.0186 0.0195 for topical use D10A X03 Azelaic acid 0.0011 0.0161 0.0172 0.0009 0.0186 0.0195

D10B Anti-acne preparations for 0.0087 0.0694 0.0782 0.0056 0.0673 0.0729 systemic use

D10B A Retinoids for treatment of acne 0.0087 0.0694 0.0782 0.0056 0.0673 0.0729 D10B A01 Isotretinoin 0.0087 0.0694 0.0782 0.0056 0.0673 0.0729

Table 7.7 Other dermatological preparations, D11 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

D11A Other dermatological 0.0302 3.4062 3.4364 0.0383 3.4883 3.5266 preparations

D11A C Medicated shampoos 0.0161 2.9619 2.9780 0.0067 3.0611 3.0678 D11A C03 Selenium compounds 0.0161 2.9619 2.9780 0.0067 3.0611 3.0678

D11A F Wart and anti-corn 0.0006 0.1898 0.1904 0.0004 0.2077 0.2081 preparations

D11A H Agents for dermatitis, 0.0029 0.0308 0.0337 0.0017 0.0201 0.0218 excluding corticosteroids D11A H01 Tacrolimus 0.0029 0.0280 0.0309 0.0017 0.0166 0.0183 D11A H02 Pimecrolimus - 0.0028 0.0028 - 0.0035 0.0035

D11A X Other dermatologicals 0.0106 0.2238 0.2343 0.0295 0.1995 0.2290 D11A X01 Minoxidil - 0.1180 0.1180 - 0.1087 0.1087 D11A X05 Magnesium sulfate 0.0106 - 0.0106 0.0295 - 0.0295 D11A X10 Finasteride - 0.0937 0.0937 - 0.0803 0.0803 D11A X11 Hydroquinone - 0.0121 0.0121 - 0.0104 0.0104

Utilisation of dermatological preparations 7.2 Preamala Gunabalasingam, Tang Min Moon, Suganthi Thevarajah

Most dermatological conditions can be treated with topical or systemic therapy. The medications include antifungals, anti-psoriatics, antibiotics, antivirals, corticosteroids, anti-acne agents and calcineurin inhibitors. This study analysed all the medications used to treat dermatological conditions in 2015 and 2016. Data collected was analysed to determine the trend of utilisation in both the public and private sectors. Topical medications remain the mainstay of treatment.

The utilisation of topical antifungals decreased from 2015 to 2016 in both public and private sectors. Concurrently, prescription of systemic antifungal increased especially terbinafine in the private sector. Topical azoles like miconazole, ketoconazole and clotrimazole were the three most commonly prescribed antifungals in the public sector. Combination of antifungal and corticosteroids was widely prescribed in the private sector compared to low usage in public hospitals.

In term of anti-psoriatics, the usage of topical preparations has been static. However, usage of calcipotriol and the fixed dose calcipotriol combination was halved from 2015 to 2016. Overall, prescription of acitretin remained low in the public sector with reduced usage from 2015 to 2016. Utilisation pattern of systemic anti-psoriatic agents could not be determined, as this data was not reported. Topical methoxsalen use was low in public hospitals and not used at all in the private sector.

There was a slight increase in the usage of topical antibiotics from 2015 to 2016. The most commonly prescribed topical antibiotics were neomycin, followed by fusidic acid and mupirocin. The use of topical acyclovir remained static over the two years. Imiquimod use was low, probably due to its high cost.

The usage of topical corticosteroids and its combination was comparable in 2015 and 2016. The three most frequently prescribed in order were betamethasone (potent), clobetasol (very potent) and hydrocortisone (weak). Prescription of betamethasone and hydrocortisone were comparable in both public and private sector. However, usage of clobetasol in the private sector was much higher than the public sector. Combination topical corticosteroid preparations (with antibiotics or other combinations) were used mainly in the private sector especially bethamethasone-antibiotics combination.

Topical treatments for acne vulgaris include benzoyl peroxide, retinoids, topical antibiotic and azelaic acid. The preference of topical anti-acne medications differed between the public and private sectors.

Topical antibiotics preparations, both single and in combination with clindamycin and erythromycin were not used in the public sector. Prescription of benzoyl peroxide, tretinoin, adapalene and azelaic acid reduced in the public sector but high or increased in the private sector. Adapalene was again the topical retinoid of choice in the private health care facilities. The use of oral isotretinoin both in the private and public sectors were comparable for both years.

Statistics on wart and anti-corn preparations use in the private sector showed marginal increase although the overall usage was low. Most of the cases were treated with physical modalities. The overall utilisation of topical calcineurin inhibitors such as tacrolimus and pimecrolimus was either reduced or low in the private sector probably due to its high cost. Pimercrolimus was not available in the public sector during these periods.

Topical minoxidil (hair growth stimulant) was not available in the public sector and its documented usage in private sector was low. The actual usage might be higher as it can be purchased over the counter. Low usage of hydroquinone in the public sector was also due to non-availability.

In conclusion, we noticed a difference in prescribing pattern between the public and the private sectors. Usage of systemic immunosuppressive agents and biological agents was not addressed as data on breakdown of prescription by Dermatologists (public and private) was not available.

8 Genito Urinary System and Sex Hormones

Statistics on medicines for genito urinary system and sex hormones 8.1

Table 8.1 Statistics by therapeutic groups for genito urinary system and sex hormones, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

G Genito urinary system and sex 6.9113 10.6885 17.5997 10.0793 10.0169 20.0962 hormones

G01 Gynecological antiinfectives 0.0584 0.2920 0.3504 0.0518 0.3163 0.3681 and antiseptics G02 Other gynecologicals 0.0507 0.0245 0.0752 0.0509 0.0314 0.0822 G03 Sex hormones and modulators 5.1826 9.4441 14.6267 8.3373 8.6904 17.0276 of the genital system G04 Urologicals 1.6195 0.9278 2.5474 1.6394 0.9789 2.6182

Table 8.2 Gynecological antiinfectives and antiseptics, G01 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

G01A Antiinfectives and antiseptics, 0.0584 0.2920 0.3504 0.0518 0.3163 0.3681 excluding combinations with corticosteroids

G01A A Antibiotics 0.0001 - 0.0001 - 0.0002 0.0002 G01A A01 Nystatin 0.0001 - 0.0001 - 0.0002 0.0002

G01A C Quinoline derivatives 0.0001 0.0017 0.0018 0.0001 0.0014 0.0016 G01A C05 Dequalinium 0.0001 0.0017 0.0018 0.0001 0.0014 0.0016

G01A F Imidazole derivatives 0.0582 0.1681 0.2264 0.0517 0.1687 0.2203 G01A F02 Clotrimazole 0.0582 0.1657 0.2239 0.0517 0.1640 0.2157 G01A F04 Miconazole - 0.0003 0.0003 - 0.0006 0.0006 G01A F05 Econazole - 0.0021 0.0021 - 0.0033 0.0033 G01A F08 Tioconazole - 0.0001 0.0001 - - - G01A F20 Combinations of imidazole - - - - 0.0008 0.0008 derivatives

G01A X Other antiinfectives and - 0.1221 0.1221 - 0.1459 0.1459 antiseptics G01A X03 Policresulen - 0.0110 0.0110 - 0.0081 0.0081 G01A X11 Povidone-iodine - 0.1111 0.1111 - 0.1378 0.1378

Table 8.3 Other gynecological drugs, G02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

G02A Uterotonics 0.0382 0.0082 0.0464 0.0392 0.0073 0.0465

G02A B Ergot alkaloids <0.0001 - <0.0001 - - - G02A B03 Ergometrine <0.0001 - <0.0001 - - -

G02A D Prostaglandins 0.0382 0.0082 0.0464 0.0392 0.0073 0.0465 G02A D02 Dinoprostone 0.0373 0.0081 0.0454 0.0385 0.0072 0.0457 G02A D03 Gemeprost 0.0007 0.0001 0.0008 0.0005 0.0001 0.0007 G02A D04 Carboprost 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0002

G02C Other gynecologicals 0.0125 0.0163 0.0288 0.0116 0.0241 0.0357

G02C B Prolactine inhibitors 0.0125 0.0163 0.0288 0.0116 0.0240 0.0357 G02C B01 Bromocriptine 0.0076 0.0123 0.0199 0.0079 0.0199 0.0278 G02C B03 Cabergoline 0.0049 0.0041 0.0089 0.0037 0.0042 0.0079

G02C X Other gynecologicals <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 G02C X01 Atosiban <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

Table 8.4 Sex hormones and modulators of the genital system, G03 (Utilisation in DDD/1,000 inhabitants /day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

G03A Hormonal contraceptives for 4.4261 7.1822 11.6083 7.6418 6.5193 14.1611 systemic use

G03A A Progestogens and estrogens, 1.4323 5.2841 6.7165 2.8882 4.8379 7.7261 fixed combinations G03A A07 Levonorgestrel and 0.6550 1.7566 2.4116 1.6194 1.5612 3.1806 ethinylestradiol G03A A09 Desogestrel and 0.7741 1.7994 2.5735 1.2644 1.8766 3.1410 ethinylestradiol G03A A10 Gestodene and <0.0001 0.3170 0.3170 - 0.2780 0.2780 ethinylestradiol G03A A12 Drospirenone and 0.0032 1.3333 1.3365 0.0043 1.0603 1.0646 ethinylestradiol G03A A13 Norelgestromin and - 0.0613 0.0613 - 0.0505 0.0505 ethinylestradiol G03A A14 Nomegestrol and estradiol - 0.0165 0.0165 - 0.0112 0.0112

G03A B Progestogens and estrogens, - 0.0156 0.0156 - 0.0149 0.0149 sequential preparations G03A B08 Dienogest and estradiol - 0.0156 0.0156 - 0.0149 0.0149

G03A C Progestogens 2.9937 1.8458 4.8395 4.7536 1.6347 6.3883 G03A C01 Norethisterone 1.0971 0.7864 1.8835 1.6351 0.6342 2.2693 G03A C06 Medroxyprogesterone 1.6554 0.5223 2.1777 2.9583 0.5052 3.4635 G03A C08 Etonogestrel 0.2400 0.4859 0.7259 0.1594 0.4452 0.6046 G03A C09 Desogestrel 0.0012 0.0512 0.0524 0.0007 0.0501 0.0508

G03A D Emergency contraceptives 0.0001 0.0367 0.0367 <0.0001 0.0318 0.0318 G03A D01 Levonorgestrel 0.0001 0.0362 0.0362 <0.0001 0.0312 0.0312 G03A D02 Ulipristal - 0.0005 0.0005 - 0.0006 0.0006

G03B Androgens 0.0175 0.0629 0.0804 0.0163 0.0520 0.0683

G03B A 3-oxoandrosten (4) derivatives 0.0175 0.0594 0.0769 0.0163 0.0487 0.0650 G03B A03 Testosterone 0.0175 0.0594 0.0769 0.0163 0.0487 0.0650

G03B B 5-androstanon (3) derivatives - 0.0035 0.0035 - 0.0033 0.0033 G03B B01 Mesterolone - 0.0035 0.0035 - 0.0033 0.0033

G03C Estrogens 0.0841 0.3388 0.4229 0.0912 0.3569 0.4481

G03C A Natural and semisynthetic 0.0605 0.2203 0.2808 0.0730 0.2275 0.3004 estrogens, plain G03C A03 Estradiol 0.0242 0.1091 0.1334 0.0175 0.1221 0.1396 G03C A57 Conjugated estrogens 0.0363 0.1112 0.1475 0.0555 0.1054 0.1609

G03C X Other estrogens 0.0236 0.1185 0.1420 0.0183 0.1294 0.1477 G03C X01 Tibolone 0.0236 0.1185 0.1420 0.0183 0.1294 0.1477

G03D Progestogens 0.4279 0.9810 1.4089 0.4528 1.0411 1.4939

G03D A Pregnen (4) derivatives 0.3371 0.2415 0.5786 0.3450 0.2736 0.6185 G03D A02 Medroxyprogesterone 0.3256 0.0589 0.3845 0.3371 0.0591 0.3962 G03D A03 Hydroxyprogesterone 0.0077 0.0871 0.0948 0.0052 0.0712 0.0764 G03D A04 Progesterone 0.0038 0.0955 0.0993 0.0026 0.1432 0.1459

G03D B Pregnadien derivatives 0.0905 0.2736 0.3641 0.1068 0.2771 0.3839 G03D B01 Dydrogesterone 0.0824 0.2416 0.3240 0.0960 0.2379 0.3339 G03D B08 Dienogest 0.0081 0.0320 0.0401 0.0107 0.0392 0.0500

Table 8.4 (continued) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

G03D C Estren derivatives 0.0004 0.4658 0.4662 0.0011 0.4904 0.4915 G03D C01 Allylestrenol - 0.0038 0.0038 - - - G03D C02 Norethisterone 0.0004 0.4620 0.4624 0.0011 0.4904 0.4915

G03F Progestogens and estrogens in 0.0680 0.1242 0.1922 0.0405 0.1142 0.1547 combination

G03F A Progestogens and estrogens, 0.0162 0.0186 0.0348 0.0087 0.0173 0.0260 fixed combinations G03F A04 Progesterone and estrogen - 0.0010 0.0010 - 0.0008 0.0008 G03F A12 Medroxyprogesterone and 0.0035 0.0028 0.0064 0.0015 0.0024 0.0040 estrogen G03F A14 Dydrogesterone and estrogen 0.0097 0.0092 0.0189 0.0048 0.0095 0.0143 G03F A17 Drospirenone and estrogen 0.0030 0.0056 0.0086 0.0024 0.0046 0.0070

G03F B Progestogens and estrogens, 0.0518 0.1056 0.1574 0.0317 0.0970 0.1287 sequential preparations G03F B01 Norgestrel and estrogen 0.0365 0.0683 0.1048 0.0202 0.0657 0.0858 G03F B08 Dydrogesterone and estrogen 0.0153 0.0372 0.0525 0.0115 0.0313 0.0428

G03G Gonadotropins and other 0.1088 0.3672 0.4760 0.0461 0.2576 0.3037 ovulation stimulants

G03G A Gonadotropins 0.0130 0.0357 0.0487 0.0114 0.0406 0.0521 G03G A01 Chorionic gonadotrophin 0.0100 0.0207 0.0307 0.0093 0.0240 0.0333 G03G A02 Human menopausal 0.0008 0.0029 0.0036 0.0006 0.0049 0.0056 gonadotrophin G03G A04 Urofollitropin 0.0004 0.0003 0.0006 0.0004 0.0002 0.0006 G03G A05 Follitropin alfa 0.0010 0.0061 0.0072 0.0006 0.0051 0.0057 G03G A06 Follitropin beta 0.0009 0.0048 0.0057 0.0004 0.0055 0.0059 G03G A08 Choriogonadotropin alfa <0.0001 0.0007 0.0007 0.0001 0.0006 0.0007 G03G A09 Corifollitropin alfa <0.0001 <0.0001 <0.0001 - <0.0001 <0.0001 G03G A30 Gonadotropins, combinations - 0.0002 0.0002 - 0.0002 0.0002

G03G B Ovulation stimulants, synthetic 0.0957 0.3315 0.4273 0.0346 0.2170 0.2516 G03G B02 Clomifene 0.0957 0.3315 0.4273 0.0346 0.2170 0.2516

G03H Antiandrogens 0.0166 0.3371 0.3537 0.0135 0.3041 0.3176

G03H A Antiandrogens, plain 0.0010 0.0040 0.0050 - 0.0037 0.0037 G03H A01 Cyproterone 0.0010 0.0040 0.0050 - 0.0037 0.0037

G03H B Antiandrogens and estrogens 0.0156 0.3331 0.3487 0.0135 0.3004 0.3139 G03H B01 Cyproterone and estrogen 0.0156 0.3331 0.3487 0.0135 0.3004 0.3139

G03X Other sex hormones and 0.0336 0.0509 0.0845 0.0351 0.0451 0.0803 modulators of the genital system

G03X A Antigonadotropins and similar 0.0070 0.0030 0.0101 0.0072 0.0031 0.0104 agents G03X A01 Danazol 0.0070 0.0030 0.0101 0.0072 0.0031 0.0104

G03X B Progesterone receptor - - - <0.0001 0.0004 0.0004 modulators G03X B02 Ulipristal - - - <0.0001 0.0004 0.0004

G03X C Selective estrogen receptor 0.0266 0.0478 0.0744 0.0279 0.0416 0.0695 modulators G03X C01 Raloxifene 0.0266 0.0478 0.0744 0.0279 0.0416 0.0695

Table 8.5 Urological drugs, G04 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

G04B Urologicals 0.0948 0.3876 0.4824 0.1016 0.3645 0.4660

G04B D Drugs for urinary frequency 0.0886 0.0552 0.1438 0.0952 0.0608 0.1560 and incontinence G04B D02 Flavoxate <0.0001 0.0114 0.0114 - 0.0134 0.0134 G04B D04 Oxybutynin 0.0019 0.0002 0.0021 0.0014 0.0002 0.0017 G04B D06 Propiverine 0.0074 0.0007 0.0082 0.0041 0.0008 0.0049 G04B D07 Tolterodine 0.0624 0.0106 0.0730 0.0708 0.0110 0.0818 G04B D08 Solifenacin 0.0075 0.0143 0.0218 0.0112 0.0119 0.0231 G04B D09 Trospium 0.0004 0.0032 0.0037 0.0003 0.0013 0.0017 G04B D10 Darifenacin <0.0001 0.0073 0.0073 - 0.0123 0.0123 G04B D11 Fesoterodine 0.0088 0.0070 0.0158 0.0073 0.0046 0.0119 G04B D12 Mirabegron - 0.0005 0.0005 - 0.0053 0.0053

G04B E Drugs used in erectile 0.0062 0.3297 0.3359 0.0063 0.3012 0.3075 dysfunction G04B E01 Alprostadil - 0.0002 0.0002 - 0.0001 0.0001 G04B E03 Sildenafil 0.0058 0.2264 0.2322 0.0061 0.1791 0.1852 G04B E08 Tadalafil 0.0003 0.0773 0.0776 0.0002 0.0973 0.0975 G04B E09 Vardenafil 0.0001 0.0215 0.0216 0.0001 0.0204 0.0205 G04B E11 Udenafil - 0.0043 0.0043 - 0.0042 0.0042

G04B X Other urologicals - 0.0027 0.0027 - 0.0024 0.0024 G04B X14 Dapoxetine - 0.0027 0.0027 - 0.0024 0.0024

G04C Drugs used in benign prostatic 1.5247 0.5402 2.0649 1.5378 0.6144 2.1522 hypertrophy

G04C A Alpha-adrenoreceptor 0.9971 0.4107 1.4078 0.9939 0.4673 1.4612 antagonists G04C A01 Alfuzosin 0.3206 0.1266 0.4473 0.3703 0.1070 0.4773 G04C A02 Tamsulosin 0.2622 0.1205 0.3827 0.2992 0.2138 0.5130 G04C A03 Terazosin 0.3113 0.0782 0.3896 0.2645 0.0654 0.3299 G04C A52 Tamsulosin and dutasteride 0.1030 0.0852 0.1882 0.0600 0.0811 0.1411

G04C B Testosterone-5-alpha 0.5276 0.1296 0.6572 0.5439 0.1471 0.6910 reductase inhibitors G04C B01 Finasteride 0.2960 0.0825 0.3784 0.3609 0.0623 0.4231 G04C B02 Dutasteride 0.2316 0.0471 0.2787 0.1830 0.0849 0.2678

Utilisation of gynecologicals, sex hormones and hormonal contraception 8.2 Nasuha Yaacob, Haliza Kamarudin, Norashikin Abdul Fuad, Vanessa Liang Lu Wen

This chapter reviews the trends in drug usage in obstetrics and gynaecology for the years 2015 to 2016.

Imidazole derivatives are shown to have higher cure rates and only require a shorter duration of treatment as compared to nystatin and hence, more favoured. Among the imidazole derivatives, clotrimazole showed the highest usage in both private and public sectors. Throughout both years, the usage in the private sector was seen to be three-fold higher as compared to the public sector, likely due to easy access of the drug as over-the-counter products at retail pharmacies and private clinics. In the public sector, only clotrimazole is available as a vaginal pessary for the treatment of vaginal candidiasis.

Overall, the use of uterotonics was seen to be four to five-fold higher in the public sector due to higher delivery rates compared to the private sector. This also explains the consistently higher usage of

dinoprostone in the public sector, for induction of labour. Besides that, most high risk deliveries requiring higher usage of uterotonics, also occur in public hospitals.

The use of carboprost was seen to be minimal with no increment throughout 2015 and 2016. It is postulated that this is attributed to the ongoing Obstetrics Life Savings Skills courses1 since 2009 that has allowed skill development of better surgical techniques as well as mechanical interventions for the prevention and management of postpartum haemorrhage (PPH), hence reducing the need for pharmacological agents. Besides that, the national Training Manual on Management of PPH was published in 2016.2

Despite the unfavourable side-effects of bromocriptine,3 the usage was still seen to be three to four-fold higher in the private sector compared to cabergoline. It was noted that the usage is higher in the private sector which can be attributed to the larger number of fertility patients in which prolactin inhibitors are used in the prevention of severe ovarian hyperstimulation syndrome (OHSS).

Pertaining to the use of hormonal contraceptives, there was a 1.3 to 2.5-fold increase in the overall use of combined contraceptives pill from 2015 to 2016 in the public sector. Besides this, the trend of parenteral medroxyprogesterone use as a long-acting reversible contraceptive (LARC) was also seen to increase, which could be due to its ease of administration, requiring a three monthly depot injection. This increase in the use of contraceptives in the public sector may be contributed by initiatives to increase family planning awareness among public primary health clinics.

Oral medroxyprogesterone had the highest usage in the public sector with a 1.8-fold increase from 2015 to 2016. It is commonly used in the treatment of abnormal uterine bleeding which is the most common gynaecological condition seen at the public sector.

The use of emergency contraceptive was much higher in the private sector as compared to the public sector where its usage is restricted solely in the one stop crisis centres (OSCC) for alleged rape victims.

Infertility affects one in four couples in developing countries and is speculated to be up trending.4 Majority of fertility centres in Malaysia are privately run. Hence, the use of estrogens was seen to be much higher in the private sector, contributed by the higher number of segmented in-vitro fertilization (IVF) treatments in the private sector, in which estrogens are used for endometrial priming prior to frozen-thaw embryo transfer (FET).

Although clomiphene citrate is still the first line agent in the management of anovulatory subfertility, there was a decrease by half in the usage in both private and public sectors. This may be attributed to early referral to assisted reproductive technology (ART) which is reflected in the increase in the usage of gonadotrophins.

REFERENCES

1. Obstetrics Life Saving Skill Course; Royal College of Obstetricians and Gynaecologists: London, 2006. 2. Postpartum Haemorrhage: Malaysian Training Manual 2016; Ministry of Health Malaysia: Kuala Lumpur, 2016. 3. dos Santos Nunes, V.; El Dib, R.; Boguszewski, C. L.; Nogueira, C. R. Cabergoline versus Bromocriptine in the Treatment of Hyperprolactinemia: a Systematic Review of Randomized Controlled Trials and Meta-analysis. Pituitary 2011, 14(3), 259-265. 4. Mascarenhas, M. N.; Flaxman, S. R.; Boerma, T.; et al. National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys. PLOS Medicine 2012, 9(12), e1001356.

9 Systemic Hormonal Preparations, excluding Sex Hormones and Insulins

Statistics on systemic hormonal preparations, excluding sex hormones and 9.1 insulins

Table 9.1 Statistics by therapeutic groups for systemic hormonal preparations, excluding sex hormones and insulins, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

H Systemic hormonal 4.4037 4.9668 9.3705 4.0812 4.9368 9.0180 preparations, excluding sex hormones and insulins

H01 Pituitary and hypothalamic 0.1196 0.0183 0.1379 0.1068 0.0202 0.1269 hormones and analogues H02 Corticosteroids for systemic use 2.5610 3.9168 6.4778 2.3627 3.8385 6.2012 H03 Thyroid therapy 1.7186 1.0058 2.7244 1.6079 1.0488 2.6567 H04 Pancreatic hormones 0.0002 <0.0001 0.0002 0.0001 <0.0001 0.0001 H05 Calcium homeostasis 0.0044 0.0259 0.0302 0.0038 0.0293 0.0331

Table 9.2 Pituitary and hypothalamic hormones and analogues, H01 (Utilisation in DDD/1,000 inhabitants /day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

H01A Anterior pituitary lobe 0.0053 0.0036 0.0088 0.0057 0.0040 0.0097 hormones and analogues

H01A A ACTH 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 H01A A02 Tetracosactide 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001

H01A B Thyrotropin <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 H01A B01 Thyrotropin alfa <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

H01A C Somatropin and somatropin 0.0051 0.0035 0.0087 0.0056 0.0040 0.0096 agonists H01A C01 Somatropin 0.0051 0.0035 0.0087 0.0056 0.0040 0.0096

H01B Posterior pituitary lobe 0.1117 0.0124 0.1242 0.0989 0.0136 0.1125 hormones

H01B A Vasopressin and analogues 0.0270 0.0024 0.0293 0.0206 0.0044 0.0250 H01B A01 Vasopressin (argipressin) 0.0071 - 0.0071 0.0077 - 0.0077 H01B A02 Desmopressin 0.0197 0.0024 0.0221 0.0128 0.0044 0.0172 H01B A04 Terlipressin 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001

H01B B Oxytocin and analogues 0.0848 0.0101 0.0949 0.0783 0.0091 0.0874 H01B B02 Oxytocin 0.0831 0.0096 0.0926 0.0771 0.0083 0.0855 H01B B03 Carbetocin 0.0017 0.0005 0.0022 0.0011 0.0008 0.0020

H01C Hypothalamic hormones 0.0025 0.0023 0.0048 0.0022 0.0025 0.0048

H01C A Gonadotropin-releasing <0.0001 - <0.0001 <0.0001 - <0.0001 hormones H01C A01 Gonadorelin <0.0001 - <0.0001 <0.0001 - <0.0001

H01C B Somatostatin and analogues 0.0024 0.0005 0.0029 0.0021 0.0005 0.0025 H01C B01 Somatostatin - <0.0001 <0.0001 - - - H01C B02 Octreotide 0.0023 0.0004 0.0027 0.0021 0.0004 0.0025 H01C B03 Lanreotide 0.0001 <0.0001 0.0001 - 0.0001 0.0001

H01C C Anti-gonadotropin-releasing 0.0001 0.0018 0.0020 0.0002 0.0021 0.0022 hormones H01C C01 Ganirelix 0.0001 0.0010 0.0011 0.0001 0.0012 0.0013 H01C C02 Cetrorelix <0.0001 0.0008 0.0008 <0.0001 0.0009 0.0009

Table 9.3 Corticosteroids for systemic use, H02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

H02A Corticosteroids for systemic 2.5610 3.9168 6.4778 2.3627 3.8385 6.2012 use, plain

H02A A Mineralocorticoids 0.0069 - 0.0069 0.0040 - 0.0040 H02A A02 Fludrocortisone 0.0069 - 0.0069 0.0040 - 0.0040

H02A B Glucocorticoids 2.5541 3.9168 6.4709 2.3587 3.8385 6.1971 H02A B01 Betamethasone - 0.1597 0.1597 - 0.1700 0.1700 H02A B02 Dexamethasone 0.4147 0.7658 1.1805 0.3485 0.7622 1.1107 H02A B04 Methylprednisolone 0.0620 0.0328 0.0948 0.0495 0.0352 0.0847 H02A B06 Prednisolone 1.5955 2.6309 4.2264 1.5117 2.5315 4.0432 H02A B07 Prednisone <0.0001 0.0001 0.0001 0.0052 0.0048 0.0099 H02A B08 Triamcinolone 0.0090 0.1651 0.1741 0.0091 0.1773 0.1864 H02A B09 Hydrocortisone 0.4730 0.1624 0.6353 0.4347 0.1574 0.5921

Table 9.4 Thyroid therapy, H03 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

H03A Thyroid preparations 1.0047 0.5221 1.5268 0.9182 0.5508 1.4690

H03A A Thyroid hormones 1.0047 0.5221 1.5268 0.9182 0.5508 1.4690 H03A A01 Levothyroxine sodium 1.0047 0.5221 1.5268 0.9182 0.5508 1.4690

H03B Antithyroid preparations 0.7139 0.4837 1.1976 0.6896 0.4980 1.1877

H03B A Thiouracils 0.0500 0.0251 0.0751 0.0569 0.0171 0.0740 H03B A02 Propylthiouracil 0.0500 0.0251 0.0751 0.0569 0.0171 0.0740

H03B B Sulfur-containing imidazole 0.6639 0.4586 1.1225 0.6327 0.4810 1.1137 derivatives H03B B01 Carbimazole 0.6631 0.4370 1.1001 0.6273 0.4650 1.0923 H03B B02 Thiamazole 0.0008 0.0216 0.0224 0.0054 0.0160 0.0214

Table 9.5 Pancreatic hormones, H04 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

H04A Glycogenolytic hormones 0.0002 <0.0001 0.0002 0.0001 <0.0001 0.0001

H04A A Glycogenolytic hormones 0.0002 <0.0001 0.0002 0.0001 <0.0001 0.0001 H04A A01 Glucagon 0.0002 <0.0001 0.0002 0.0001 <0.0001 0.0001

Table 9.6 Agents for calcium homeostasis, H05 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

H05A Parathyroid hormones and 0.0002 0.0160 0.0162 0.0009 0.0179 0.0188 analogues

H05A A Parathyroid hormones and 0.0002 0.0160 0.0162 0.0009 0.0179 0.0188 analogues H05A A02 Teriparatide 0.0002 0.0160 0.0162 0.0009 0.0179 0.0188

H05B Anti-parathyroid agents 0.0042 0.0098 0.0141 0.0029 0.0114 0.0143

H05B A Calcitonin preparations 0.0017 0.0019 0.0036 0.0011 0.0022 0.0033 H05B A01 Calcitonin (salmon synthetic) 0.0017 0.0019 0.0036 0.0011 0.0022 0.0033

H05B X Other anti-parathyroid agents 0.0025 0.0080 0.0105 0.0018 0.0092 0.0110 H05B X01 Cinacalcet 0.0005 0.0010 0.0015 0.0006 0.0021 0.0027 H05B X02 Paricalcitol 0.0020 0.0070 0.0090 0.0012 0.0070 0.0082

Utilisation of systemic hormonal preparations 9.2 Zanariah Hussein, Nor Afidah Karim, Vijiya Mala Valayatham, Danish Ng Ooi Yee, Wong Hui Chin, Navin Kumar Loganadan, Daphne Gima

In Malaysia, the total consumption for endocrine-related drugs showed a decline from 2015 (9.3705 DDD/1,000 inhabitants/day) to 2016 (9.0181 DDD/1,000 inhabitants/day) representing a decrease of 3.8%. This decline is mostly from the reduction in the utilisation of desmopressin and glucocorticoids, respectively by 22.2% and 4.2%.

There is no change in the utilisation of adrenocorticotropic hormone (ACTH) and thyrotropin between 2015 and 2016. However, there is an increase in the utilisation of somatropin by 10.3% in 2016, probably reflecting better access to growth hormone therapy for the specific indications. There is a reduced utilisation of desmopressin in public sector by 35.0%, as opposed to 83.3% increment in the private sector. The utilisation of gonadorelin from 2015 to 2016 remains low. The utilisation of somatostatin analogues has reduced even with improved detection of related diseases, with higher octreotide utilisation in public sector.

In general, there is an overall reduction in the utilisation of corticosteroids by 4.3%, which is more apparent in the public sector (7.7%) between the two years. The utilisation of fludrocortisone has dropped by 42.0% and exclusively utilised in the public sector. There is a marked decline of 16.0% in the utilisation of dexamethasone in the public sector. Prednisone utilisation, although very small, has increased almost 100- fold from 0.0001 DDD/1,000 inhabitants/day to 0.0099 DDD/1,000 inhabitants/day.

The overall utilisation of levothyroxine has reduced sequentially from 2015 to 2016 by 3.8%, as compared to the increasing trend of utilisation between 2011 and 2014. In 2015, the utilisation of levothyroxine in the public sector in Malaysia was very much lower (1.0047 DDD/1,000 inhabitants/day) compared to Australia under Pharmaceutical Benefits Scheme (PBS) (11.6693 DDD/1,000 inhabitants/day). The difference between these two countries may be due to the practice of lower prescribed doses in Malaysia. The utilisation of propylthiouracil in 2015 and 2016 has reduced markedly by almost 40% compared to previous years. This is expected in view of the recommendations for restricted prescribing following reports of life- threatening acute hepatoxicity globally. Carbimazole remains the most commonly prescribed antithyroid drug, with more than 90% utilisation.

Glucagon utilisation remains low between 2015 and 2016, indicated mainly for correction of severe hypoglycaemia. The utilisation of teriparatide is very much higher in the private sector compared to the public sector, 95.2% versus 4.8% in 2016. Teriparatide utilisation, although remains low, has shown 4.5-fold increase in the public sector. Calcitonin utilisation remains low with not much change between 2015 and 2016. Cinacalcet utilisation increased by 80.0%, primarily driven by the doubling of utilisation in private sector.

Utilisation of systemic glucocorticoids in rheumatology 9.3 Gun Suk Chyn, Mollyza Mohd Zain, Liza Mohd Isa, Chong Hwee Cheng, Siti Rabiatul Adawiyah

Systemic glucocorticoids usage in Malaysia in 2015 was 6.4709 DDD/1,000 inhabitants/day (Table 9.3). However, there was a reduction of 4.2% to 6.1971 DDD/1,000 inhabitants/day in 2016. Reduction in the usage of systemic glucocorticoids in 2016 was largely contributed by 7.7% lower utilisation by the public sector. The use of systemic glucocorticoids in Malaysia is very much lower than that reported in Finland where the utilisations for systemic corticosteroids were 18.87 and 19.15 DDD/1,000 inhabitants/day in 2015 and 2016, respectively.

Prednisolone was the most commonly used glucocorticoids and contributed to 65% of the total glucocorticoids usage in 2015 and 2016. Of this, about 60% was used in the private sector. However, there was an overall reduction of 4.3% in prednisolone usage with DDD/1,000 inhabitants/day of 4.2264 in 2015 to 4.0432 in 2016. The reduction was 3.8% in the private sector and 5.3% in public sector (Table 9.3).

Dexamethasone was the second most commonly used glucocorticoids and accounted for approximately 18% of the total usage. The usage remained fairly stable with DDD/1,000 inhabitants/day of 1.1805 in 2015 and 1.1107 in 2016. Hydrocortisone was the third most commonly used glucocorticoids and it contributed almost 9% of total usage with DDD/1,000 inhabitants/day of 0.6353 and 0.5921 in 2015 and 2016, respectively (Table 9.3). The usage of betamethasone, methylprednisolone and triamcinolone remained low, accounting for less than 10% of the total glucocorticoid used.

10 Antiinfectives for Systemic Use

Statistics on antiinfectives for systemic use 10.1

Table 10.1 Statistics by therapeutic groups of antiinfectives for systemic use, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

J Antiinfectives for systemic use 5.8555 8.1368 13.9923 5.5997 7.7225 13.3222

J01 Antibacterials for systemic use 3.3678 7.5133 10.8810 3.0980 7.1376 10.2356 J02 Antimycotics for systemic use 0.0700 0.0930 0.1630 0.0418 0.0818 0.1236 J04 Antimycobacterials 0.6305 0.0764 0.7070 0.5427 0.0881 0.6308 J05 Antivirals for systemic use 0.9871 0.2463 1.2334 1.2096 0.2021 1.4117 J07 Vaccines 0.8001 0.2079 1.0080 0.7076 0.2129 0.9205

Table 10.2 Statistics by therapeutic groups of antiinfectives for systemic use, in public and private sector (Utilisation in DDD/inhabitant/year) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

J Antiinfectives for systemic use 2.1373 2.9699 5.1072 2.0638 2.8264 4.8903

J01 Antibacterials for systemic use 1.2292 2.7423 3.9716 1.1339 2.6124 3.7462 J02 Antimycotics for systemic use 0.0256 0.0339 0.0595 0.0153 0.0299 0.0452 J04 Antimycobacterials 0.2301 0.0279 0.2580 0.1986 0.0322 0.2309 J05 Antivirals for systemic use 0.3603 0.0899 0.4502 0.4427 0.0740 0.5167 J07 Vaccines 0.2920 0.0759 0.3679 0.2733 0.0779 0.3512

Table 10.3 Tetracyclines, J01A ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01A Tetracyclines 0.2466 0.7124 0.9590 0.1851 0.7527 0.9378 0.0900 0.2600 0.3500 0.0677 0.2755 0.3432

J01A A Tetracyclines 0.2466 0.7124 0.9590 0.1851 0.7527 0.9378 0.0900 0.2600 0.3500 0.0677 0.2755 0.3432 J01A A02 Doxycycline 0.2419 0.6460 0.8878 0.1819 0.6932 0.8750 0.0883 0.2358 0.3241 0.0666 0.2537 0.3203 J01A A06 Oxytetracycline <0.0001 <0.0001 0.0001 <0.0001 - <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 - <0.0001 J01A A07 Tetracycline 0.0044 0.0646 0.0690 0.0031 0.0571 0.0602 0.0016 0.0236 0.0252 0.0011 0.0209 0.0220 J01A A08 Minocycline 0.0003 0.0015 0.0018 0.0001 0.0022 0.0023 0.0001 0.0005 0.0006 <0.0001 0.0008 0.0008 J01A A12 Tigecycline 0.0001 0.0003 0.0004 <0.0001 0.0003 0.0003 <0.0001 0.0001 0.0001 <0.0001 0.0001 0.0001

Table 10.4 Amphenicols, J01B ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016

62 Public Private Total Public Private Total Public Private Total Public Private Total

J01B Amphenicols <0.0001 0.0021 0.0021 <0.0001 0.0060 0.0060 <0.0001 0.0008 0.0008 <0.0001 0.0022 0.0022

J01B A Amphenicols <0.0001 0.0021 0.0021 <0.0001 0.0060 0.0060 <0.0001 0.0008 0.0008 <0.0001 0.0022 0.0022 J01B A01 Chloramphenicol <0.0001 0.0021 0.0021 <0.0001 0.0060 0.0060 <0.0001 0.0008 0.0008 <0.0001 0.0022 0.0022

Table 10.5 Beta-lactam antibacterials, penicillins, J01C ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01C Beta-lactam 2.1665 3.2515 5.4180 2.1024 3.2652 5.3675 0.7908 1.1868 1.9776 0.7695 1.1950 1.9645 antibacterials, penicillins

J01C A Penicillins with 1.1833 1.8093 2.9925 1.1423 1.7429 2.8852 0.4319 0.6604 1.0923 0.4181 0.6379 1.0560 extended spectrum J01C A01 Ampicillin 0.0309 0.0336 0.0645 0.0240 0.0340 0.0580 0.0113 0.0123 0.0235 0.0088 0.0124 0.0212 J01C A04 Amoxicillin 1.1254 1.6975 2.8229 1.1055 1.6164 2.7219 0.4108 0.6196 1.0303 0.4046 0.5916 0.9962 J01C A06 Bacampicillin 0.0269 0.0782 0.1052 0.0128 0.0925 0.1053 0.0098 0.0285 0.0384 0.0047 0.0338 0.0385

J01C E Beta-lactamase 0.0852 0.0203 0.1055 0.0598 0.0049 0.0647 0.0311 0.0074 0.0385 0.0219 0.0018 0.0237 sensitive penicillins J01C E01 Benzylpenicillin 0.0201 0.0010 0.0211 0.0188 0.0008 0.0196 0.0073 0.0003 0.0077 0.0069 0.0003 0.0072 J01C E02 Phenoxymethylpenicillin 0.0632 0.0193 0.0825 0.0392 0.0040 0.0431 0.0231 0.0071 0.0301 0.0143 0.0015 0.0158 J01C E08 Benzathine 0.0008 <0.0001 0.0009 0.0008 0.0001 0.0009 0.0003 <0.0001 0.0003 0.0003 <0.0001 0.0003 63 benzylpenicillin J01C E09 Procaine 0.0010 - 0.0010 0.0010 - 0.0010 0.0004 - 0.0004 0.0004 - 0.0004 benzylpenicillin

J01C F Beta-lactamase 0.5403 0.1589 0.6992 0.5184 0.1659 0.6843 0.1972 0.0580 0.2552 0.1897 0.0607 0.2504 resistant penicillins J01C F02 Cloxacillin 0.5403 0.1589 0.6992 0.5184 0.1659 0.6843 0.1972 0.0580 0.2552 0.1897 0.0607 0.2504

J01C R Combinations of 0.3577 1.2630 1.6208 0.3818 1.3516 1.7334 0.1306 0.4610 0.5916 0.1398 0.4947 0.6344 penicillins, including beta-lactamase inhibitors J01C R01 Ampicillin and beta- 0.0131 0.0049 0.0180 0.0136 0.0043 0.0179 0.0048 0.0018 0.0066 0.0050 0.0016 0.0065 lactamase inhibitor J01C R02 Amoxicillin and beta- 0.2824 1.1993 1.4817 0.2999 1.2880 1.5879 0.1031 0.4377 0.5408 0.1098 0.4714 0.5812 lactamase inhibitor J01C R04 Sultamicillin 0.0486 0.0574 0.1059 0.0455 0.0575 0.1030 0.0177 0.0209 0.0387 0.0167 0.0210 0.0377 J01C R05 Piperacillin and beta- 0.0137 0.0015 0.0152 0.0229 0.0017 0.0246 0.0050 0.0005 0.0055 0.0084 0.0006 0.0090 lactamase inhibitor

Table 10.6 Other beta-lactam antibacterials, J01D ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01D Other beta-lactam 0.4558 1.3145 1.7703 0.4246 1.3494 1.7740 0.1664 0.4798 0.6462 0.1554 0.4939 0.6493 antibacterials

J01D B First-generation 0.0901 0.5660 0.6561 0.0838 0.5590 0.6428 0.0329 0.2066 0.2395 0.0307 0.2046 0.2353 cephalosporins J01D B01 Cefalexin 0.0876 0.5039 0.5915 0.0822 0.5270 0.6092 0.0320 0.1839 0.2159 0.0301 0.1929 0.2230 J01D B04 Cefazolin 0.0025 0.0010 0.0035 0.0015 0.0011 0.0026 0.0009 0.0004 0.0013 0.0006 0.0004 0.0010 J01D B05 Cefadroxil - 0.0611 0.0611 - 0.0309 0.0309 - 0.0223 0.0223 - 0.0113 0.0113

J01D C Second-generation 0.2641 0.6658 0.9299 0.2535 0.7090 0.9625 0.0964 0.2430 0.3394 0.0928 0.2595 0.3523 cephalosporins J01D C02 Cefuroxime 0.2641 0.6278 0.8919 0.2535 0.6832 0.9366 0.0964 0.2292 0.3255 0.0928 0.2500 0.3428 J01D C04 Cefaclor - 0.0380 0.0380 - 0.0258 0.0258 - 0.0139 0.0139 - 0.0094 0.0094

J01D D Third-generation 0.0706 0.0711 0.1417 0.0641 0.0694 0.1336 0.0258 0.0259 0.0517 0.0235 0.0254 0.0489 64 cephalosporins J01D D01 Cefotaxime 0.0025 0.0005 0.0030 0.0024 0.0004 0.0028 0.0009 0.0002 0.0011 0.0009 0.0001 0.0010 J01D D02 Ceftazidime 0.0125 0.0014 0.0139 0.0111 0.0010 0.0121 0.0046 0.0005 0.0051 0.0041 0.0004 0.0044 J01D D04 Ceftriaxone 0.0484 0.0364 0.0849 0.0438 0.0388 0.0826 0.0177 0.0133 0.0310 0.0160 0.0142 0.0302 J01D D08 Cefixime - 0.0054 0.0054 - 0.0039 0.0039 - 0.0020 0.0020 - 0.0014 0.0014 J01D D12 Cefoperazone 0.0067 0.0003 0.0071 0.0062 0.0003 0.0065 0.0025 0.0001 0.0026 0.0023 0.0001 0.0024 J01D D14 Ceftibuten - 0.0155 0.0155 - 0.0142 0.0142 - 0.0056 0.0056 - 0.0052 0.0052 J01D D15 Cefdinir <0.0001 0.0077 0.0077 <0.0001 0.0059 0.0059 <0.0001 0.0028 0.0028 <0.0001 0.0021 0.0022 J01D D62 Cefoperazone and 0.0005 0.0038 0.0043 0.0005 0.0050 0.0055 0.0002 0.0014 0.0016 0.0002 0.0018 0.0020 beta-lactamase inhibitor

J01D E Fourth-generation 0.0126 0.0003 0.0129 0.0097 0.0005 0.0102 0.0046 0.0001 0.0047 0.0035 0.0002 0.0037 cephalosporins J01D E01 Cefepime 0.0126 0.0003 0.0129 0.0097 0.0005 0.0102 0.0046 0.0001 0.0047 0.0035 0.0002 0.0037

J01D H Carbapenems 0.0185 0.0111 0.0295 0.0135 0.0112 0.0247 0.0067 0.0040 0.0108 0.0049 0.0041 0.0091 J01D H02 Meropenem 0.0117 0.0076 0.0193 0.0093 0.0079 0.0171 0.0043 0.0028 0.0071 0.0034 0.0029 0.0063 J01D H03 Ertapenem 0.0024 0.0022 0.0046 0.0008 0.0022 0.0030 0.0009 0.0008 0.0017 0.0003 0.0008 0.0011 J01D H04 Doripenem <0.0001 0.0002 0.0002 <0.0001 0.0003 0.0003 <0.0001 0.0001 0.0001 <0.0001 0.0001 0.0001

Table 10.6 (continued) ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01D H51 Imipenem and 0.0044 0.0010 0.0054 0.0034 0.0009 0.0043 0.0016 0.0004 0.0020 0.0013 0.0003 0.0016 cilastatin

J01D I Other cephalosporins <0.0001 0.0002 0.0002 <0.0001 0.0002 0.0002 <0.0001 0.0001 0.0001 <0.0001 0.0001 0.0001 and penems J01D I02 Ceftaroline fosamil <0.0001 0.0002 0.0002 <0.0001 0.0002 0.0002 <0.0001 0.0001 0.0001 <0.0001 0.0001 0.0001

Table 10.7 Sulfonamides and trimethoprim, J01E ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01E Sulfonamides and 0.1043 0.0839 0.1881 0.0881 0.0764 0.1645 0.0381 0.0306 0.0687 0.0322 0.0280 0.0602 65

trimethoprim

J01E A Trimethoprim and 0.0009 - 0.0009 0.0003 0.0004 0.0007 0.0003 - 0.0003 0.0001 0.0001 0.0003 derivatives J01E A01 Trimethoprim 0.0009 - 0.0009 0.0003 0.0004 0.0007 0.0003 - 0.0003 0.0001 0.0001 0.0003

J01E E Combinations of 0.1034 0.0839 0.1873 0.0877 0.0760 0.1638 0.0377 0.0306 0.0683 0.0321 0.0278 0.0599 sulfonamides and trimethoprim, including derivatives J01E E01 Sulfamethoxazole and 0.1034 0.0839 0.1873 0.0877 0.0760 0.1638 0.0377 0.0306 0.0683 0.0321 0.0278 0.0599 trimethoprim

Table 10.8 Macrolides, lincosamides and streptogramins, J01F ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01F Macrolides, 0.2899 1.3011 1.5910 0.2087 1.3038 1.5125 0.1058 0.4749 0.5807 0.0764 0.4772 0.5536 lincosamides and streptogramins

J01F A Macrolides 0.2807 1.2925 1.5731 0.2016 1.2960 1.4976 0.1024 0.4717 0.5742 0.0738 0.4743 0.5481 J01F A01 Erythromycin 0.2004 0.2308 0.4312 0.1367 0.2643 0.4011 0.0731 0.0842 0.1574 0.0500 0.0967 0.1468 J01F A06 Roxithromycin - 0.0328 0.0328 - 0.0246 0.0246 - 0.0120 0.0120 - 0.0090 0.0090 J01F A09 Clarithromycin 0.0188 0.5185 0.5372 0.0235 0.4818 0.5053 0.0069 0.1892 0.1961 0.0086 0.1763 0.1849 J01F A10 Azithromycin 0.0615 0.5104 0.5719 0.0413 0.5253 0.5666 0.0225 0.1863 0.2087 0.0151 0.1923 0.2074

J01F F Lincosamides 0.0092 0.0087 0.0179 0.0071 0.0078 0.0149 0.0034 0.0032 0.0065 0.0026 0.0028 0.0055 J01F F01 Clindamycin 0.0092 0.0058 0.0150 0.0071 0.0063 0.0134 0.0034 0.0021 0.0055 0.0026 0.0023 0.0049 J01F F02 Lincomycin - 0.0029 0.0029 - 0.0015 0.0015 - 0.0011 0.0011 - 0.0005 0.0005

66 Table 10.9 Aminoglycoside antibacterials, J01G ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01G Aminoglycoside 0.0175 0.0043 0.0218 0.0129 0.0040 0.0169 0.0064 0.0016 0.0080 0.0047 0.0014 0.0062 antibacterials

J01G A Streptomycins 0.0050 - 0.0050 0.0029 - 0.0029 0.0018 - 0.0018 0.0011 - 0.0011 J01G A01 Streptomycin 0.0050 - 0.0050 0.0029 - 0.0029 0.0018 - 0.0018 0.0011 - 0.0011

J01G B Other aminoglycosides 0.0125 0.0043 0.0168 0.0100 0.0040 0.0140 0.0046 0.0016 0.0061 0.0037 0.0014 0.0051 J01G B03 Gentamicin 0.0088 0.0025 0.0114 0.0076 0.0024 0.0099 0.0032 0.0009 0.0041 0.0028 0.0009 0.0036 J01G B04 Kanamycin 0.0007 0.0013 0.0019 0.0005 0.0009 0.0014 0.0002 0.0005 0.0007 0.0002 0.0003 0.0005 J01G B06 Amikacin 0.0029 0.0004 0.0033 0.0019 0.0005 0.0024 0.0011 0.0001 0.0012 0.0007 0.0002 0.0009 J01G B07 Netilmicin 0.0001 0.0001 0.0002 0.0001 0.0002 0.0002 <0.0001 <0.0001 0.0001 <0.0001 0.0001 0.0001

Table 10.10 Quinolone antibacterials, J01M ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01M Quinolone 0.0395 0.8287 0.8682 0.0333 0.3677 0.4010 0.0144 0.3025 0.3169 0.0122 0.1346 0.1468 antibacterials

J01M A Fluoroquinolones 0.0395 0.8216 0.8611 0.0333 0.3637 0.3971 0.0144 0.2999 0.3143 0.0122 0.1331 0.1453 J01M A01 Ofloxacin 0.0065 0.0168 0.0233 0.0046 0.0137 0.0183 0.0024 0.0061 0.0085 0.0017 0.0050 0.0067 J01M A02 Ciprofloxacin 0.0270 0.6650 0.6921 0.0223 0.1870 0.2093 0.0099 0.2427 0.2526 0.0082 0.0684 0.0766 J01M A06 Norfloxacin - 0.0166 0.0166 - 0.0128 0.0128 - 0.0060 0.0060 - 0.0047 0.0047 J01M A07 Lomefloxacin - 0.0045 0.0045 - 0.0014 0.0014 - 0.0016 0.0016 - 0.0005 0.0005 J01M A12 Levofloxacin 0.0052 0.0852 0.0904 0.0061 0.1165 0.1225 0.0019 0.0311 0.0330 0.0022 0.0426 0.0449 J01M A14 Moxifloxacin 0.0008 0.0335 0.0343 0.0004 0.0324 0.0327 0.0003 0.0122 0.0125 0.0001 0.0119 0.0120

J01M B Other quinolones - 0.0071 0.0071 - 0.0040 0.0040 - 0.0026 0.0026 - 0.0014 0.0014 J01M B04 Pipemidic acid - 0.0071 0.0071 - 0.0040 0.0040 - 0.0026 0.0026 - 0.0014 0.0014

Table 10.11 Other antibacterials, J01X ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J01X Other antibacterials 0.0477 0.0148 0.0624 0.0429 0.0125 0.0554 0.0174 0.0054 0.0228 0.0157 0.0046 0.0203

J01X A Glycopeptide 0.0054 0.0004 0.0058 0.0045 0.0006 0.0051 0.0020 0.0002 0.0021 0.0016 0.0002 0.0019 antibacterials J01X A01 Vancomycin 0.0053 0.0002 0.0055 0.0045 0.0004 0.0049 0.0019 0.0001 0.0020 0.0016 0.0002 0.0018 J01X A02 Teicoplanin <0.0001 0.0002 0.0003 <0.0001 0.0002 0.0002 <0.0001 0.0001 0.0001 <0.0001 0.0001 0.0001

J01X B Polymyxins 0.0031 0.0001 0.0031 0.0018 0.0002 0.0020 0.0011 <0.0001 0.0011 0.0007 0.0001 0.0007 J01X B01 Colistin 0.0029 0.0001 0.0030 0.0017 0.0002 0.0019 0.0011 <0.0001 0.0011 0.0006 0.0001 0.0007 J01X B02 Polymyxin B 0.0002 - 0.0002 0.0001 - 0.0001 0.0001 - 0.0001 <0.0001 - <0.0001

J01X C Steroid antibacterials 0.0081 0.0004 0.0084 0.0075 0.0006 0.0081 0.0029 0.0001 0.0031 0.0027 0.0002 0.0030 J01X C01 Fusidic acid 0.0081 0.0004 0.0084 0.0075 0.0006 0.0081 0.0029 0.0001 0.0031 0.0027 0.0002 0.0030

J01X D Imidazole derivatives 0.0284 0.0052 0.0336 0.0285 0.0051 0.0336 0.0104 0.0019 0.0123 0.0104 0.0019 0.0123 68 J01X D01 Metronidazole 0.0284 0.0052 0.0336 0.0285 0.0051 0.0336 0.0104 0.0019 0.0123 0.0104 0.0019 0.0123

J01X E Nitrofuran derivatives 0.0022 0.0037 0.0059 0.0004 0.0009 0.0012 0.0008 0.0014 0.0022 0.0001 0.0003 0.0004 J01X E01 Nitrofurantoin 0.0022 0.0037 0.0059 0.0004 0.0009 0.0012 0.0008 0.0014 0.0022 0.0001 0.0003 0.0004

J01X X Other antibacterials 0.0006 0.0049 0.0055 0.0002 0.0051 0.0053 0.0002 0.0018 0.0020 0.0001 0.0019 0.0020 J01X X01 Fosfomycin <0.0001 0.0041 0.0041 <0.0001 0.0041 0.0041 <0.0001 0.0015 0.0015 <0.0001 0.0015 0.0015 J01X X04 Spectinomycin - - - - <0.0001 <0.0001 - - - - <0.0001 <0.0001 J01X X08 Linezolid 0.0006 0.0008 0.0014 0.0002 0.0010 0.0011 0.0002 0.0003 0.0005 0.0001 0.0004 0.0004 J01X X09 Daptomycin <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 J01X X11 Tedizolid - - - - <0.0001 <0.0001 - - - - <0.0001 <0.0001

Table 10.12 Antimycotics for systemic use, J02 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J02A Antimycotics for 0.0700 0.0930 0.1630 0.0418 0.0818 0.1236 0.0256 0.0339 0.0595 0.0153 0.0299 0.0452 systemic use

J02A A Antibiotics 0.0022 0.0001 0.0022 0.0027 0.0001 0.0028 0.0008 <0.0001 0.0008 0.0010 <0.0001 0.0010 J02A A01* Amphotericin B 0.0022 0.0001 0.0022 0.0027 0.0001 0.0028 0.0008 <0.0001 0.0008 0.0010 <0.0001 0.0010

J02A B Imidazole derivatives 0.0125 0.0095 0.0221 0.0036 0.0043 0.0079 0.0046 0.0035 0.0081 0.0013 0.0016 0.0029 J02A B02 Ketoconazole 0.0125 0.0095 0.0221 0.0036 0.0043 0.0079 0.0046 0.0035 0.0081 0.0013 0.0016 0.0029

J02A C Triazole derivatives 0.0545 0.0832 0.1377 0.0344 0.0773 0.1118 0.0199 0.0304 0.0503 0.0126 0.0283 0.0409 J02A C01 Fluconazole 0.0248 0.0562 0.0810 0.0207 0.0550 0.0757 0.0090 0.0205 0.0296 0.0076 0.0201 0.0277 J02A C02 Itraconazole 0.0290 0.0266 0.0556 0.0125 0.0220 0.0345 0.0106 0.0097 0.0203 0.0046 0.0080 0.0126 J02A C03 Voriconazole 0.0005 0.0002 0.0007 0.0010 0.0002 0.0012 0.0002 0.0001 0.0002 0.0004 0.0001 0.0004 J02A C04 Posaconazole 0.0003 0.0002 0.0005 0.0002 0.0002 0.0003 0.0001 0.0001 0.0002 0.0001 0.0001 0.0001

69 J02A X Other antimycotics for 0.0009 0.0001 0.0010 0.0010 0.0002 0.0012 0.0003 0.0001 0.0004 0.0004 0.0001 0.0004 systemic use J02A X01 Flucytosine 0.0001 - 0.0001 <0.0001 - <0.0001 <0.0001 - <0.0001 <0.0001 - <0.0001 J02A X04 Caspofungin 0.0004 <0.0001 0.0004 0.0005 <0.0001 0.0006 0.0001 <0.0001 0.0002 0.0002 <0.0001 0.0002 J02A X05 Micafungin <0.0001 <0.0001 <0.0001 - <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 - <0.0001 <0.0001 J02A X06 Anidulafungin 0.0003 0.0001 0.0004 0.0005 0.0001 0.0006 0.0001 <0.0001 0.0002 0.0002 <0.0001 0.0002

* Utilisation for conventional formulation of amphotericin B (J02A A01) is shown, excluding lipophilic products.

Table 10.13 Antimycobacterials, J04 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J04A Drugs for treatment of 0.5702 0.0706 0.6408 0.5121 0.0832 0.5953 0.2081 0.0258 0.2339 0.1874 0.0305 0.2179 tuberculosis

J04A B Antibiotics 0.1985 0.0045 0.2030 0.1579 0.0082 0.1661 0.0725 0.0016 0.0741 0.0578 0.0030 0.0608 J04A B01 Cycloserine 0.0015 - 0.0015 0.0006 - 0.0006 0.0005 - 0.0005 0.0002 - 0.0002

Table 10.13 (continued) ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J04A B02 Rifampicin 0.1970 0.0045 0.2015 0.1573 0.0082 0.1655 0.0719 0.0016 0.0735 0.0576 0.0030 0.0606 J04A B04 Rifabutin 0.0001 - 0.0001 <0.0001 - <0.0001 <0.0001 - <0.0001 <0.0001 - <0.0001

J04A C Hydrazides 0.2370 0.0294 0.2664 0.1988 0.0198 0.2186 0.0865 0.0107 0.0972 0.0727 0.0072 0.0800 J04A C01 Isoniazid 0.2370 0.0294 0.2664 0.1988 0.0198 0.2186 0.0865 0.0107 0.0972 0.0727 0.0072 0.0800

J04A D Thiocarbamide 0.0014 - 0.0014 0.0012 - 0.0012 0.0005 - 0.0005 0.0004 - 0.0004 derivatives J04A D03 Ethionamide 0.0014 - 0.0014 0.0012 - 0.0012 0.0005 - 0.0005 0.0004 - 0.0004

J04A K Other drugs for 0.0449 0.0164 0.0613 0.0563 0.0260 0.0822 0.0164 0.0060 0.0224 0.0206 0.0095 0.0301 treatment of tuberculosis J04A K01 Pyrazinamide 0.0275 0.0093 0.0367 0.0321 0.0152 0.0473 0.0100 0.0034 0.0134 0.0118 0.0055 0.0173

J04A K02 Ethambutol 0.0174 0.0072 0.0245 0.0241 0.0108 0.0350 0.0063 0.0026 0.0090 0.0088 0.0040 0.0128 7

0 J04A M Combinations of drugs 0.0884 0.0203 0.1087 0.0979 0.0293 0.1272 0.0323 0.0074 0.0397 0.0358 0.0107 0.0466 for treatment of tuberculosis J04A M02 Rifampicin and 0.0262 0.0045 0.0307 0.0370 0.0197 0.0567 0.0096 0.0016 0.0112 0.0135 0.0072 0.0207 isoniazid J04A M05 Rifampicin, - 0.0037 0.0037 0.0005 0.0012 0.0018 - 0.0014 0.0014 0.0002 0.0005 0.0007 pyrazinamide and isoniazid J04A M06 Rifampicin, 0.0622 0.0121 0.0743 0.0604 0.0083 0.0688 0.0227 0.0044 0.0271 0.0221 0.0030 0.0252 pyrazinamide, ethambutol and isoniazid

J04B Drugs for treatment of 0.0603 0.0058 0.0661 0.0306 0.0048 0.0355 0.0220 0.0021 0.0241 0.0112 0.0018 0.0130 lepra

J04B A Drugs for treatment of 0.0603 0.0058 0.0661 0.0306 0.0048 0.0355 0.0220 0.0021 0.0241 0.0112 0.0018 0.0130 lepra J04B A01 Clofazimine 0.0016 - 0.0016 0.0018 - 0.0018 0.0006 - 0.0006 0.0007 - 0.0007 J04B A02 Dapsone 0.0587 0.0058 0.0645 0.0288 0.0048 0.0337 0.0214 0.0021 0.0235 0.0106 0.0018 0.0123

Table 10.14 Antivirals for systemic use, J05 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J05A Direct acting antivirals 0.9871 0.2463 1.2334 1.2096 0.2021 1.4117 0.3603 0.0899 0.4502 0.4427 0.0740 0.5167

J05A B Nucleosides and 0.0160 0.0826 0.0986 0.0130 0.0412 0.0542 0.0058 0.0302 0.0360 0.0048 0.0151 0.0198 nucleotides excluding reverse transcriptase inhibitors J05A B01 Aciclovir 0.0151 0.0794 0.0944 0.0123 0.0382 0.0505 0.0055 0.0290 0.0345 0.0045 0.0140 0.0185 J05A B06 Ganciclovir 0.0004 <0.0001 0.0005 0.0004 <0.0001 0.0004 0.0002 <0.0001 0.0002 0.0001 <0.0001 0.0001 J05A B11 Valaciclovir <0.0001 0.0031 0.0031 <0.0001 0.0028 0.0028 <0.0001 0.0011 0.0011 <0.0001 0.0010 0.0010 J05A B14 Valganciclovir 0.0005 0.0001 0.0006 0.0003 0.0001 0.0005 0.0002 <0.0001 0.0002 0.0001 0.0001 0.0002

J05A E Protease inhibitors 0.0023 0.0003 0.0026 0.0004 0.0002 0.0007 0.0008 0.0001 0.0009 0.0002 0.0001 0.0002 J05A E01 Saquinavir <0.0001 <0.0001 <0.0001 - - - <0.0001 <0.0001 <0.0001 - - - J05A E02 Indinavir 0.0003 <0.0001 0.0003 - - - 0.0001 <0.0001 0.0001 - - - J05A E03 Ritonavir 0.0003 0.0002 0.0004 <0.0001 0.0001 0.0001 0.0001 0.0001 0.0002 <0.0001 <0.0001 <0.0001 71 J05A E10 Darunavir 0.0016 0.0001 0.0018 0.0004 0.0001 0.0006 0.0006 <0.0001 0.0006 0.0002 <0.0001 0.0002

J05A F Nucleoside and 0.2465 0.1204 0.3669 0.1749 0.1137 0.2886 0.0900 0.0439 0.1339 0.0640 0.0416 0.1056 nucleotide reverse transcriptase inhibitors J05A F01 Zidovudine 0.0055 <0.0001 0.0055 0.0038 <0.0001 0.0039 0.0020 <0.0001 0.0020 0.0014 <0.0001 0.0014 J05A F02 Didanosine 0.0024 - 0.0024 0.0009 - 0.0009 0.0009 - 0.0009 0.0003 - 0.0003 J05A F04 Stavudine 0.0008 - 0.0008 - - - 0.0003 - 0.0003 - - - J05A F05 Lamivudine 0.0091 0.0027 0.0118 0.0188 0.0035 0.0222 0.0033 0.0010 0.0043 0.0069 0.0013 0.0081 J05A F06 Abacavir 0.0046 <0.0001 0.0046 0.0035 <0.0001 0.0035 0.0017 <0.0001 0.0017 0.0013 <0.0001 0.0013 J05A F07 Tenofovir disoproxil 0.1757 0.0103 0.1860 0.1029 0.0158 0.1186 0.0641 0.0038 0.0679 0.0376 0.0058 0.0434 J05A F08 Adefovir dipivoxil 0.0027 0.0051 0.0078 0.0027 0.0014 0.0042 0.0010 0.0019 0.0029 0.0010 0.0005 0.0015 J05A F10 Entecavir 0.0348 0.0929 0.1277 0.0361 0.0866 0.1226 0.0127 0.0339 0.0466 0.0132 0.0317 0.0449 J05A F11 Telbivudine 0.0110 0.0093 0.0203 0.0062 0.0065 0.0127 0.0040 0.0034 0.0074 0.0023 0.0024 0.0047

J05A G Non-nucleoside 0.3143 0.0170 0.3313 0.5362 0.0124 0.5486 0.1147 0.0062 0.1209 0.1963 0.0045 0.2008 reverse transcriptase inhibitors J05A G01 Nevirapine 0.0848 0.0001 0.0849 0.0751 <0.0001 0.0751 0.0310 <0.0001 0.0310 0.0275 <0.0001 0.0275 J05A G03 Efavirenz 0.2288 0.0169 0.2457 0.4608 0.0122 0.4730 0.0835 0.0062 0.0897 0.1686 0.0045 0.1731 J05A G05 Rilpivirine 0.0007 <0.0001 0.0007 0.0004 0.0002 0.0005 0.0002 <0.0001 0.0003 0.0001 0.0001 0.0002

Table 10.14 (continued) ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

J05A H Neuraminidase 0.0035 0.0118 0.0153 0.0018 0.0184 0.0202 0.0013 0.0043 0.0056 0.0007 0.0067 0.0074 inhibitors J05A H01 Zanamivir - 0.0001 0.0001 - <0.0001 <0.0001 - <0.0001 <0.0001 - <0.0001 <0.0001 J05A H02 Oseltamivir 0.0035 0.0118 0.0153 0.0018 0.0184 0.0202 0.0013 0.0043 0.0056 0.0007 0.0067 0.0074

J05A P Antivirals for treatment 0.0001 0.0006 0.0006 <0.0001 0.0011 0.0011 <0.0001 0.0002 0.0002 <0.0001 0.0004 0.0004 of HCV infections J05A P01 Ribavirin 0.0001 0.0004 0.0005 <0.0001 0.0006 0.0007 <0.0001 0.0002 0.0002 <0.0001 0.0002 0.0002 J05A P03 Boceprevir - <0.0001 <0.0001 - - - - <0.0001 <0.0001 - - - J05A P08 Sofosbuvir - - - - 0.0001 0.0001 - - - - <0.0001 <0.0001 J05A P09 Dasabuvir - 0.0001 0.0001 - 0.0002 0.0002 - <0.0001 <0.0001 - 0.0001 0.0001 J05A P53 Ombitasvir, - 0.0001 0.0001 - 0.0002 0.0002 - <0.0001 <0.0001 - 0.0001 0.0001 paritaprevir and ritonavir

72 J05A R Antivirals for treatment 0.3924 0.0129 0.4053 0.4754 0.0137 0.4891 0.1432 0.0047 0.1479 0.1740 0.0050 0.1790 of HIV infections, combinations J05A R01 Zidovudine and 0.1396 0.0026 0.1422 0.1864 0.0021 0.1885 0.0510 0.0009 0.0519 0.0682 0.0008 0.0690 lamivudine J05A R02 Lamivudine and 0.0155 0.0011 0.0166 0.0140 0.0012 0.0152 0.0057 0.0004 0.0061 0.0051 0.0004 0.0056 abacavir J05A R03 Tenofovir disoproxil 0.2024 0.0039 0.2063 0.2134 0.0051 0.2185 0.0739 0.0014 0.0753 0.0781 0.0019 0.0800 and emtricitabine J05A R06 Emtricitabine, tenofovir - - - 0.0207 - 0.0207 - - - 0.0076 - 0.0076 disoproxil and efavirenz J05A R07 Stavudine, lamivudine 0.0052 - 0.0052 0.0052 - 0.0052 0.0019 - 0.0019 0.0019 - 0.0019 and nevirapine J05A R10 Lopinavir and ritonavir 0.0297 0.0054 0.0351 0.0357 0.0053 0.0409 0.0108 0.0020 0.0128 0.0131 0.0019 0.0150

J05A X Other antivirals 0.0120 0.0007 0.0127 0.0078 0.0013 0.0092 0.0044 0.0003 0.0046 0.0029 0.0005 0.0034 J05A X08 Raltegravir 0.0120 0.0007 0.0126 0.0078 0.0009 0.0088 0.0044 0.0002 0.0046 0.0029 0.0003 0.0032 J05A X12 Dolutegravir <0.0001 <0.0001 <0.0001 <0.0001 0.0004 0.0004 <0.0001 <0.0001 <0.0001 <0.0001 0.0001 0.0001

Table 10.15 Vaccines, J07 and bacterial vaccines, J07A (Utilisation in dose/year) ATC code Vaccine 2015 2016 Public Private Total Public Private Total

J07 Vaccines 9,107,709 2,366,168 11,473,877 8,192,166 2,464,966 10,657,132

J07A Bacterial vaccines 4,118,330 1,356,351 5,474,681 3,373,395 1,391,111 4,764,506

J07A E Cholera vaccines 1,595 7,165 8,760 1,915 4,149 6,064 J07A E01 Cholera, inactivated, 1,595 7,165 8,760 1,915 4,149 6,064 whole cell

J07A G Hemophilus influenzae 1,201 3,103 4,304 1,272 221 1,493 B vaccines J07A G01 Hemophilus influenzae 1,201 3,103 4,304 1,272 221 1,493 B, purified antigen conjugated

J07A H Meningococcal 36,015 188,715 224,730 28,786 180,770 209,556 vaccines J07A H04 Meningococcus 35,660 4,410 40,070 27,400 80 27,480 A,C,Y,W-135, tetravalent purified polysaccharides antigen J07A H08 Meningococcus 355 184,305 184,660 1,386 180,690 182,076 A,C,Y,W-135, tetravalent purified polysaccharides antigen conjugated

J07A J Pertussis vaccines 350 4,414 4,764 - 6,244 6,244 J07A J52 Pertussis, purified 350 4,414 4,764 - 6,244 6,244 antigen, combinations with toxoids

J07A L Pneumococcal 6,534 185,939 192,473 6,471 185,380 191,851 vaccines J07A L01 Pneumococcus, 4,740 21,531 26,271 3,851 16,520 20,371 purified polysaccharides antigen J07A L02 Pneumococcus, 1,699 137,182 138,881 2,620 146,963 149,583 purified polysaccharides antigen conjugated J07A L52 Pneumococcus 95 27,226 27,321 - 21,897 21,897 purified polysaccharides antigen and haemophilus influenzae, conjugated

J07A M Tetanus vaccines 2,955,900 279,350 3,235,250 2,412,500 250,299 2,662,799 J07A M01 Tetanus toxoid 2,460,400 272,170 2,732,570 1,821,500 241,329 2,062,829 J07A M51 Tetanus toxoid, 495,500 7,180 502,680 591,000 8,970 599,970 combinations with diphtheria toxoid

J07A N Tuberculosis vaccines 925,000 448,900 1,373,900 815,000 438,900 1,253,900 J07A N01 Tuberculosis, live 925,000 448,900 1,373,900 815,000 438,900 1,253,900 attenuated

Table 10.15 (continued) ATC code Vaccine 2015 2016 Public Private Total Public Private Total

J07A P Typhoid vaccines 191,735 238,765 430,500 107,451 325,148 432,599 J07A P01 Typhoid, oral, live - 2,700 2,700 - 3,417 3,417 attenuated J07A P03 Typhoid, purified 191,735 236,065 427,800 107,451 321,731 429,182 polysaccharide antigen

Table 10.16 Viral vaccines, J07B (Utilisation in dose/year) ATC code Vaccine 2015 2016 Public Private Total Public Private Total

J07B Viral vaccines 3,283,739 861,366 4,145,105 3,150,881 855,552 4,006,433

J07B A Encephalitis vaccines 77,425 15,959 93,384 96,805 16,968 113,773 J07B A02 Encephalitis, - 1,847 1,847 - 965 965 Japanese, inactivated, whole virus J07B A03 Encephalitis, 77,425 14,112 91,537 96,805 16,003 112,808 Japanese, live attenuated

J07B B Influenza vaccines 85,982 184,960 270,942 61,906 188,698 250,604 J07B B01 Influenza, inactivated, 2,389 41,400 43,789 1,837 18,243 20,080 whole virus J07B B02 Influenza, inactivated, 83,593 143,560 227,153 60,069 170,455 230,524 split virus or surface antigen

J07B C Hepatitis vaccines 1,437,116 410,795 1,847,911 1,334,067 384,271 1,718,338 J07B C01 Hepatitis B, purified 1,436,681 344,284 1,780,965 1,334,067 365,915 1,699,982 antigen - Paediatric 1,355,706 221,118 1,576,824 1,281,441 244,031 1,525,472 - Adult 80,975 123,166 204,141 52,626 121,884 174,510 J07B C02 Hepatitis A, 435 55,587 56,022 - 5,743 5,743 inactivated, whole virus J07B C20 Hepatitis A and - 10,924 10,924 - 12,613 12,613 hepatitis B

J07B D Measles vaccines 934,770 74,588 1,009,358 1,389,362 82,789 1,472,151 J07B D01 Measles, live 267,500 900 268,400 302,000 - 302,000 attenuated J07B D52 Measles, combinations 465,820 73,581 539,401 825,412 75,911 901,323 with mumps and rubella, live attenuated J07B D53 Measles, combinations 201,450 - 201,450 261,950 - 261,950 with rubella, live attenuated J07B D54 Measles, combinations - 107 107 - 6,878 6,878 with mumps, rubella and varicella, live attenuated

Table 10.16 (continued) ATC code Vaccine 2015 2016 Public Private Total Public Private Total

J07B F Poliomyelitis vaccines 296,000 130 296,130 - 110 110 J07B F02 Poliomyelitis oral, 296,000 130 296,130 - 110 110 trivalent, live attenuated

J07B G Rabies vaccines 5,538 1,547 7,085 2,837 1,541 4,378 J07B G01 Rabies, inactivated, 5,538 1,547 7,085 2,837 1,541 4,378 whole virus

J07B H Rota virus diarrhea 200 70,437 70,637 85 78,337 78,422 vaccines J07B H01 Rota virus, live 200 70,437 70,637 85 78,337 78,422 attenuated

J07B J Rubella vaccines 2,300 - 2,300 - - - J07B J01 Rubella, live 2,300 - 2,300 - - - attenuated

J07B K Varicella zoster 4 59,980 59,984 21 64,426 64,447 vaccines J07B K01 Varicella, live 4 59,980 59,984 21 64,426 64,447 attenuated

J07B L Yellow fever vaccines 2,048 3,707 5,755 140 4,651 4,791 J07B L01 Yellow fever, live 2,048 3,707 5,755 140 4,651 4,791 attenuated

J07B M Papillomavirus 442,356 39,263 481,619 265,658 33,761 299,419 vaccines J07B M01 Papillomavirus (human 442,336 33,878 476,214 265,648 31,730 297,378 types 6, 11, 16, 18) J07B M02 Papillomavirus (human 20 5,385 5,405 10 2,031 2,041 types 16, 18)

Table 10.17 Bacterial and viral vaccines in combination, J07C (Utilisation in dose/year) ATC code Vaccine 2015 2016 Public Private Total Public Private Total

J07C Bacterial and viral 1,705,640 148,451 1,854,091 1,667,890 218,303 1,886,193 vaccines, combined

J07C A Bacterial and viral 1,705,640 148,451 1,854,091 1,667,890 218,303 1,886,193 vaccines, combined J07C A02 Diphtheria-pertussis- - 6,986 6,986 - - - poliomyelitis-tetanus J07C A06 Diphtheria-Hemophilus 1,705,640 76,994 1,782,634 1,667,890 168,595 1,836,485 influenzae B-pertussis- poliomyelitis-tetanus J07C A09 Diphtheria-Hemophilus - 63,750 63,750 - 49,185 49,185 influenzae B-pertussis- poliomyelitis-tetanus- hepatitis B J07C A10 Typhoid-hepatitis A - 721 721 - 523 523

Utilisation of systemic antiinfectives 10.2 Leong Chee Loon, Steven Lim Chee Loon, Rahela Ambaras Khan, Preethi Raghavan, Hannah Md Mahir, Mak Woh Yon

Anti-infectives are amongst the most commonly used drugs in Malaysian health facilities. With the advent of more invasive procedures and immune-modulatory therapy, infections have become a major cause of morbidity and mortality. In view of limited new anti-infective agents in the pipeline, the judicious use of anti-infectives is vital to preserve the efficacy of the agents. In addition, accurate diagnosis and adequate source control are equally important to minimise the emergence of resistant organisms. The value presented in this chapter is based on DDD/per inhabitant/year.

Antibacterials

Cephalosporins are workhorse antibiotics commonly used in healthcare facilities throughout Malaysia. The largest usage of this group of antibacterials in year 2015 and 2016 was contributed by second- generation cephalosporins, mainly cefuroxime, with a 5.3% increment in 2016, driven by the usage in the private sector (Table 10.6). Overall, the largest increase in usage of cephalosporins was observed in cefoperazone/beta-lactamase inhibitor, despite having a relatively low utilisation. The 25.0% increment was mainly contributed by the private sector. However, the usage of other third-generation cephalosporins, such as ceftriaxone and ceftazidime has reduced.

Piperacillin/beta-lactamase inhibitor usage increased by 63.6% from year 2015 to 2016 (Table 10.5). In contrast, cefepime had a 21.3% reduction in usage. This could be due to a shift of choice of anti- pseudomonal agents, both in targeted and empirical therapy. This trend is likely to persist as many studies had shown that piperacillin/beta-lactamase inhibitor is a carbapenem-sparing option for multi-resistant organisms, such as extended spectrum beta-lactamases (ESBL) producing organisms.

In contrast to previous years, there is a 15.7% decline in usage of carbapenems, mainly observed in the public sector (Table 10.6). This could be attributed to the effort of antimicrobial stewardship (AMS) programme in public hospitals initiated by the MoH since 2014.

Among the fluoroquinolones, levofloxacin remained the only agent that continues to rise in usage (36% from year 2015 to 2016). This may be due to the increased usage of levofloxacin as a second line anti- tuberculosis (TB) agent in the setting of drug-induced hepatitis or multidrug resistant (MDR) TB.

The usage of polymyxins had reduced by 36.4% (Table 10.11) despite the increasing number of carbapenem-resistant enterobacteriaceae (CRE) isolates from year 2015 to 2016 as shown in the national surveillance data (National Antimicrobial Guideline 2019). The rise in CRE isolates may be due to the increased effort of CRE surveillance in public hospitals nationwide and may not represent the number of true pathogens. Thus, the reduction of polymyxins usage could be due to AMS effort in monitoring usage of polymyxins and distinguishing CRE pathogens from colonizers, which do not require antibiotic treatment.

Vancomycin, being the mainstay of antimethicillin-resistant Staphylacoccus aurues (MRSA) treatment in the public sector, saw a decrease in usage of 10.0%. This is consistent with the national surveillance data which reported a reduced number of MRSA isolates from year 2015 to 2016. On the other hand, the usage of linezolid continues to increase in the private sector.

Antimycotics

With regards to antimycotics, broad spectrum agents have shown an increase in usage from 2015 to 2016 in the public sector. There is a 25.0% increment of amphotericin B usage and two-fold increase in voriconazole usage. Apart from voriconazole, other azoles usage has reduced about 20%.

The increase in the usage of broad-spectrum antimycotics may be due to the increase in the number of critically-ill and immunocompromised patients. This is a concern as it might show an increase in non- albicans and aspergillosis cases. Furthermore, the emergence of fusarium and cryptococcosis cases might have led to the increased usage of broad-spectrum antimycotics.

Antivirals

There were increases in usage of fixed-dose combinations (FDCs) such as tenofovir/emtricitabine (6.2%) and use of a new three-drug FDC, tenofovir/emtricitabine/efavirenz in the public sector in 2016. This trend is consistent with WHO recommendation on first line antiretroviral regimen. Efavirenz continued to be the preferred non-nucleoside reverse transcriptase inhibitor with a two-fold increase in the year 2016 compared to its equivalent, nevirapine which shows a decline.

Utilisation of lopinavir/ritonavir, which is the preferred second line anti-retroviral, increased 17.2% from 2015 to 2016. This reflects an increasing number of HIV patients and first line anti-retroviral regimen failure.

A substantial increase in the utilisation of integrase inhibitor dolutegravir was noted in 2016 (Table 10.14). This may be due to increasing evidence on dolutegravir with regards to tolerability, ease of administration and high barrier for resistance.

Oseltamivir saw an increase in utilisation of approximately 32.1% in 2016. Zanamivir, however, showed very low usage. Both oseltamivir and zanamivir were largely used in the private sector due to the availability of diagnostic kits for influenza in the private sector. With increased promotion of vaccination as well as postexposure vaccination which is relatively inexpensive and have demonstrated clinical effectiveness, the utilisation of acyclovir is noted to have a decline of 46.4% from 2015 to 2016.

Anti-tuberculosis

The most common anti-tuberculosis drugs being used were isoniazid and rifampicin, respectively 36.7% and 27.8% in 2016. Over the two years, the usage of antimycobacterial had decreased in public sector about 10%. However, there is an increase in usage of 18.2% in the private sector. This may reflect that private healthcare providers were more involved in TB care. In the public sector, FDC of isoniazid and rifampicin were preferred over the individual rifampicin and isoniazid.

Utilisation of drugs for viral hepatitis C 10.3 Rosaida Md Said, Zalwani Zainuddin, Norasiah Abu Bakar, Tan Soek Siam, Muhammad Radzi Abu Hassan

In 2015 and 2016, the approved direct-acting antivirals (DAA) for the treatment of hepatitis C were boceprevir, sofosbuvir, dasabuvir and combination of ombitasvir, paritaprevir and ritonavir. Only a very small number of these medicines were prescribed in both private and public sectors. The usage of DAA had increased in year 2016 (0.0011 DDD/1,000 inhabitants/day) compared to year 2015 (0.0006 DDD/ 1,000 inhabitants/day). Even though chronic hepatitis C has caused a huge burden in Malaysia, the most likely reason for the low prescription of DAAs was the high cost of these medicines.

Utilisation of vaccines 10.4 Rohani Jahis, Jamiatul Aida Md Sani, Najwa Ahmad Hamdi

Vaccination is a well-known cost effective and safe method in disease control. National Immunisation Programme (NIP) in Malaysia was established in 1972 with only five antigens covered by vaccines. Since then, until 2016, five vaccines were in the NIP covering 11 pathogens and a vaccine for Japanese encephalitis (JE) only given to children in Sarawak. High immunisation coverage for each vaccine is essential in order to ensure herd immunity and to achieve the goals stated in Global Vaccine Action Plan (GVAP).1

Overall, the trend of bacterial vaccines consumptions was more as compared to viral vaccines or combined bacterial-viral vaccines (Table 10.15, 10.16 and 10.17). Procurement of tuberculosis vaccine which come in multidose preparation was double the number of estimated birth cohort (500,000), taking into account the wastage following open vial policy and once open it must be used within six hours.2 The usage for cholera vaccine in 2015 was noted to be higher as compared to 2016, probably in response to

big flood that occurred in end of 2014 to early 2015. The private sector continued to use conjugated meningococcal vaccine with reduction of polysaccharide vaccine usage. There was four-fold rise in the number of conjugated meningococcal vaccine procured in public sector in 2016 as compared to 2015 because of shortage of multidose meningococcal vaccine supply.

Policies on immunisation programme does have effects on the pattern of vaccines consumption or supply. In March 2016, an administrative order from the Secretary General of Ministry of Health (MoH) notifying that MoH facilities to stop supplying typhoid and yellow fever vaccines.3 Following this order, the consumption of yellow fever vaccine dropped drastically; meanwhile to typhoid fever the number was less as compared to 2015 as MoH had to honour the stock available in the concession. In May 2015, the Director General (DG) of Health issued an order to stop using oral polio vaccine (OPV) as to prevent polio cases from the live attenuated polio virus in OPV.4 Following that, there was no OPV use in public facilities, however there was 110 doses being prescribed in private facilities.

In December 2015, the National Committee for Policy and Practice on Vaccines had approved the proposal to change the measles vaccination schedule from one and seven years old, to nine and 12 months old.5 This step was taken as to reduce the number of measles cases among children less than one year old and to reduce the gap between the first and second dose of measles immunisation schedule. As an impact, the number of measles-mumps-rubella (MMR) vaccine consumption double in 2016. The change of schedule also gave an opportunity for children to get two doses of mumps vaccination. The measles schedule for children in Standard 1 will continue until the year 2022; when the cohort that have received two doses of vaccine enters primary school. It has shown by the similar number of doses consumed in 2015 and 2016.

Government tender also has an impact on the trend of vaccine usage in NIP. Human papilloma virus (HPV) quadrivalent vaccine was used by MoH in 2014 until early 2016. The quadrivalent vaccine was also a preferred vaccine in the private sector.

Knowledge on the vaccine consumption in private sector contributes to understanding the acceptance of publics for these vaccines. These are relatively new and expensive vaccines that have not been introduced in the public sector. The vaccines were conjugated meningococcal vaccine, conjugated pneumococcal vaccine, rotavirus and varicella vaccines. Their trend of consumption noted to be slightly increased in 2016 as compared to the previous year. It indicated that advocacy by the private health sector and vaccines manufacturers has increased the awareness of the public to seek for the vaccines. In 2015 and 2016, the consumption of pneumococcal conjugated vaccine (PCV) 13-valent was noted to accelerate (Figure 10.1) in public sector, probably following the recommendation by American Thoracic Society and America Advisory Committee on Immunisation Practice (ACIP),6 the physicians prescribed PCV-13 for high risk patients. The trend of usage for PCV-23 did not change significantly in 2015 and 2016.

Understanding the epidemiology of vaccine preventable diseases explained the increase consumption of certain vaccines. Following measles outbreaks in a few states including Terengganu, Kelantan and Pahang; measles monovalent vaccine usage was slightly higher in 2016 as compared to 2015. It was used in supplementary immunisation activities (SIA) in order to curb the outbreaks. The consumption of MMR and varicella combined vaccine in private sector has jumped 68 times in 2016 as compared to the previous years, only 107 doses; indicating that the private practitioner has been advocating varicella in children. It was following multiple chicken pox outbreaks especially involving the kindergartens. Meanwhile, there was a high usage of diphtheria-pertussis-tetanus-polio vaccine in private sector in 2015 as compared to 2016 following diphtheria outbreaks in 2015, involving children and adults. It was given as a booster. Rabies vaccine usage in public sector was notably high in 2015 (Table 10.18) following rabies outbreak among animals in the Northern Peninsular Malaysia i.e. Perlis, Kedah and Pulau Pinang. The vaccine was given to animal bite cases, particularly by dogs and cats.

In conclusion, the trend of presumed consumption of vaccines both in the private and public sectors was in accordance to policy changes, local epidemiology of vaccine preventable diseases and government procurement procedures, especially for multidose vaccine. The consumptions data also gave some ideas on the acceptability of vaccines by public and the coverage of vaccination.

160,000 3,000 Number of doses used in of Numberdosessector in used public

140,000 2,500

120,000

2,000 100,000

80,000 1,500

60,000 1,000

40,000

500

20,000 Number of doses used in privatesector used in doses ofNumber 0 0 2011 2012 2013 2014 2015 2016 Private PCV-13 Private PCV-10 Public PCV-13 Public PCV-10

Figure 10.1 Trend of pneumococcal conjugated vaccine (PCV) consumption, 2011-2016 (Utilisation in dose/year)

Table 10.18 The consumption of rabies vaccine in Malaysia, 2011-2016 (Utilisation in dose/year) Year 2011 2012 2013 2014 2015 2016 Public 604 931 1,218 924 5,538 2,837 Private 1,250 2,012 1,409 1,309 1,547 1,541 Total 1,854 2,943 2,627 2,233 7,085 4,378

REFERENCES

1. Regional Framework for Implementation of the Global Vaccine Action Plan in the Western Pacific 2013-2020; Regional Office for the Western Pacific: World Health Organization. 2. Panduan Program Imunisasi Kebangsaan Bayi dan Kanak-kanak untuk Anggota Kejururawatan 2008; Family Health Development Division, Ministry of Health Malaysia: Putrajaya, 2008. 3. Secretary General of Health’s Circular. Surat Pekeliling Ketua Setiausaha Kementerian Kesihatan Malaysia Bil. 1 Tahun 2016: Pelaksanaan Langkah-langkah Mengoptimumkan Perbelanjaan Kementerian Kesihatan Malaysia; Ministry of Health Malaysia, March 14, 2016. 4. Director General of Health’s Circular. Surat Pekeliling Ketua Pengarah Kesihatan Malaysia Bll. 8 Tahun 2015: Pemberhentian Pemberian Vaksin Oral Polio (OPV) di Malaysia; Ministry of Health Malaysia, May 29, 2015. 5. Director General of Health’s Circular. Surat Pekeliling Ketua Pengarah Kesihatan Malaysia Bll. 13 Tahun 2015: Perubahan Jadual Imunisasi Measles (Demam Campak) untuk Kanak-kanak di Malaysia; Ministry of Health Malaysia, December 15, 2015. 6. Berical, A. C.; Harris, D.; Dela Cruz, C. S.; Possick, J. D. Pneumococcal Vaccination Strategies. An Update and Perspective. Ann. Am. Thorac. Soc. 2016, 13(6), 933‐944, doi:10.1513/AnnalsATS.201511- 778F.

11 Antineoplastic and Immunomodulating Agents

Statistics on antineoplastic and immunomodulating agents 11.1

Table 11.1 Statistics by therapeutic groups of antineoplastic and immunomodulating agents, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

L Antineoplastic and 76.2853 35.2270 111.5122 83.7548 37.2774 121.0322 immunomodulating agents

L01 Antineoplastic agents 75.5349 34.8580 110.3929 82.9096 36.8675 119.7771 L02 Endocrine therapy 0.3567 0.2012 0.5579 0.3582 0.2282 0.5864 L03 Immunostimulants 0.0209 0.0075 0.0284 0.0150 0.0077 0.0227 L04 Immunosuppressants 0.3728 0.1602 0.5330 0.4721 0.1740 0.6460

Table 11.2 Alkylating agents, L01A ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in total cycle/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

L01 Antineoplastic agents 75.5349 34.8580 110.3929 82.9096 36.8675 119.7771 172,322 88,368 260,690 179,542 103,320 282,863

L01A Alkylating agents 2.0845 0.6456 2.7301 2.4047 0.6757 3.0804 20,784 5,927 26,711 16,473 6,654 23,127

L01A A Nitrogen mustard 1.9260 0.5833 2.5093 2.2937 0.6048 2.8985 19,203 5,539 24,741 15,558 6,212 21,770 analogues L01A A01 Cyclophosphamide 1.9166 0.5788 2.4955 1.4930 0.5961 2.0891 16,782 5,068 21,851 13,297 5,308 18,605 L01A A02 Chlorambucil 0.0024 0.0005 0.0029 0.0036 0.0006 0.0042 198 41 239 297 47 344 L01A A03 Melphalan 0.0041 0.0013 0.0054 0.0039 0.0030 0.0069 938 285 1,223 898 704 1,602 L01A A06 Ifosfamide 0.0015 0.0002 0.0016 0.0012 0.0002 0.0014 1,284 144 1,428 1,066 152 1,218 L01A A09 Bendamustine 0.0013 0.0025 0.0039 0.7920 0.0049 0.7970 ------

L01A B Alkyl sulfonates 0.0084 0.0012 0.0096 0.0071 0.0011 0.0083 120 17 137 103 17 120 L01A B01 Busulfan 0.0084 0.0012 0.0096 0.0071 0.0011 0.0083 120 17 137 103 17 120

L01A C Ethylene imines 0.0010 - 0.0010 0.0001 - 0.0001 149 - 149 14 - 14

L01A C01 Thiotepa 0.0010 - 0.0010 0.0001 - 0.0001 149 - 149 14 - 14

L01A D Nitrosoureas 0.0022 - 0.0022 0.0005 - 0.0005 135 - 135 29 - 29 L01A D02 Lomustine 0.0022 - 0.0022 0.0005 - 0.0005 135 - 135 29 - 29

L01A X Other alkylating 0.1469 0.0610 0.2079 0.1033 0.0698 0.1731 1,178 371 1,549 769 426 1,195 agents L01A X03 Temozolomide 0.0193 0.0291 0.0484 0.0265 0.0345 0.0610 61 92 153 85 111 196 L01A X04 Dacarbazine 0.1276 0.0319 0.1595 0.0768 0.0353 0.1121 1,117 279 1,396 684 315 998

Table 11.3 Antimetabolites, L01B ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in total cycle/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

L01B Antimetabolites 25.1520 22.9318 48.0838 31.0549 22.5614 53.6164 37,705 12,005 49,710 36,005 12,735 48,740

L01B A Folic acid analogues 0.6516 0.1452 0.7968 0.8175 0.1787 0.9962 2,457 1,018 3,475 3,054 1,153 4,207 L01B A01 Methotrexate 0.6177 0.0905 0.7083 0.7831 0.1234 0.9065 2,009 294 2,303 2,590 408 2,999 L01B A04 Pemetrexed 0.0338 0.0547 0.0885 0.0344 0.0553 0.0898 448 724 1,172 464 745 1,209

L01B B Purine analogues 0.7848 0.1178 0.9025 0.7927 0.0980 0.8908 10,647 1,594 12,241 10,853 1,340 12,193 L01B B02 Mercaptopurine 0.7287 0.1121 0.8408 0.7065 0.0973 0.8038 9,645 1,484 11,129 9,512 1,310 10,821 L01B B03 Tioguanine 0.0495 0.0047 0.0542 0.0817 0.0002 0.0819 655 63 717 1,100 2 1,102 L01B B05 Fludarabine 0.0065 0.0009 0.0074 0.0045 0.0005 0.0050 347 47 394 242 28 270 L01B B06 Clofarabine <0.0001 <0.0001 0.0001 - 0.0001 0.0001 ------

L01B C Pyrimidine analogues 23.7157 22.6688 46.3845 29.4447 22.2847 51.7294 24,601 9,393 33,994 22,097 10,242 32,339 L01B C01 Cytarabine 1.9822 0.1272 2.1094 1.4763 0.1258 1.6020 1,093 70 1,163 828 71 899 L01B C02 Fluorouracil 3.8405 1.0095 4.8500 3.6697 0.9915 4.6612 12,858 3,380 16,237 12,496 3,376 15,873 82 L01B C05 Gemcitabine 2.2566 0.4948 2.7514 1.2311 0.6456 1.8768 7,467 1,637 9,104 4,144 2,173 6,317 L01B C06 Capecitabine 15.5146 20.8336 36.3481 23.0030 20.0089 43.0118 2,934 3,939 6,873 4,424 3,848 8,272 L01B C07 Azacitidine 0.0027 0.0055 0.0082 0.0038 0.0049 0.0087 ------L01B C08 Decitabine 0.0014 0.0015 0.0029 0.0018 0.0011 0.0030 90 100 190 124 76 199 L01B C53 Tegafur, combinations 0.1177 0.1968 0.3145 0.0590 0.5069 0.5659 160 267 426 81 699 780

Table 11.4 Plant alkaloids and other natural products, L01C ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in total cycle/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

L01C Plant alkaloids and 0.3000 0.1545 0.4545 0.2855 0.2111 0.4965 14,768 8,576 23,344 16,069 11,109 27,178 other natural products

L01C A Vinca alkaloids and 0.0062 0.0104 0.0166 0.0066 0.0127 0.0193 5,660 2,687 8,347 5,785 3,188 8,974 analogues L01C A01 Vinblastine 0.0020 0.0007 0.0026 0.0029 0.0011 0.0040 1,128 373 1,500 1,700 623 2,323 L01C A02 Vincristine 0.0015 0.0004 0.0019 0.0013 0.0004 0.0018 4,225 1,254 5,479 3,809 1,274 5,083 L01C A04 Vinorelbine 0.0027 0.0093 0.0120 0.0024 0.0112 0.0135 308 1,060 1,368 277 1,292 1,569

L01C B Podophyllotoxin 0.1737 0.0430 0.2167 0.1340 0.0471 0.1812 2,299 569 2,868 1,805 634 2,439 derivatives L01C B01 Etoposide 0.1737 0.0430 0.2167 0.1340 0.0471 0.1812 2,299 569 2,868 1,805 634 2,439

L01C D Taxanes 0.1201 0.1011 0.2212 0.1448 0.1513 0.2961 6,809 5,320 12,129 8,479 7,286 15,765 L01C D01 Paclitaxel 0.0749 0.0717 0.1466 0.0875 0.1231 0.2106 2,842 2,719 5,561 3,377 4,751 8,129 83 L01C D02 Docetaxel 0.0452 0.0293 0.0745 0.0573 0.0280 0.0853 3,958 2,564 6,522 5,099 2,497 7,596 L01C D04 Cabazitaxel <0.0001 0.0001 0.0002 <0.0001 0.0001 0.0001 9 38 47 3 38 41

L01C X Other plant alkaloids - <0.0001 <0.0001 - <0.0001 <0.0001 ------and natural products L01C X01 Trabectedin - <0.0001 <0.0001 - <0.0001 <0.0001 ------

Table 11.5 Cytotoxic antibiotics and related substances, L01D ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in total cycle/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

L01D Cytotoxic antibiotics 0.1885 0.0469 0.2354 0.1790 0.0532 0.2321 22,828 5,522 28,349 21,196 7,023 28,219 and related substances

L01D A Actinomycines 0.0001 - 0.0001 0.0001 - 0.0001 598 - 598 683 - 683 L01D A01 Dactinomycin 0.0001 - 0.0001 0.0001 - 0.0001 598 - 598 683 - 683

L01D B Anthracyclines and 0.1756 0.0404 0.2160 0.1684 0.0487 0.2172 17,392 4,264 21,656 16,558 5,265 21,823 related substances L01D B01 Doxorubicin 0.0577 0.0192 0.0769 0.0476 0.0242 0.0717 7,294 2,430 9,724 6,120 3,108 9,228 L01D B02 Daunorubicin 0.0084 0.0012 0.0096 0.0099 0.0012 0.0111 417 59 476 498 59 556 L01D B03 Epirubicin 0.1084 0.0196 0.1280 0.1096 0.0231 0.1327 9,491 1,715 11,205 9,757 2,061 11,818 L01D B06 Idarubicin 0.0002 0.0002 0.0004 0.0011 0.0002 0.0013 22 22 45 122 20 142 L01D B07 Mitoxantrone 0.0009 0.0002 0.0011 0.0003 0.0001 0.0004 167 39 206 60 17 78

84 L01D C Other cytotoxic 0.0129 0.0065 0.0193 0.0104 0.0044 0.0149 4,839 1,257 6,096 3,956 1,758 5,714 antibiotics L01D C01 Bleomycin 0.0090 0.0059 0.0149 0.0073 0.0030 0.0103 1,135 749 1,884 942 385 1,328 L01D C03 Mitomycin 0.0039 0.0005 0.0044 0.0031 0.0014 0.0045 3,703 508 4,212 3,013 1,372 4,386

Table 11.6 Other antineoplastic agents, L01X ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in total cycle/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

L01X Other antineoplastic 47.8099 11.0793 58.8891 48.9856 13.3661 62.3517 76,238 56,337 132,576 89,799 65,800 155,600 agents

L01X A Platinum compounds 0.6704 0.2769 0.9474 0.5437 0.3620 0.9057 26,007 11,012 37,019 26,832 14,303 41,136 L01X A01 Cisplatin 0.0997 0.0274 0.1271 0.0897 0.0271 0.1169 8,727 2,401 11,127 7,993 2,416 10,409 L01X A02 Carboplatin 0.4901 0.1944 0.6844 0.2999 0.2584 0.5582 11,157 4,425 15,582 6,944 5,982 12,926 L01X A03 Oxaliplatin 0.0807 0.0552 0.1359 0.1541 0.0765 0.2306 6,123 4,187 10,310 11,896 5,905 17,801

L01X B Methylhydrazines 0.0176 - 0.0176 0.0380 - 0.0380 95 - 95 210 - 210 L01X B01 Procarbazine 0.0176 - 0.0176 0.0380 - 0.0380 95 - 95 210 - 210

L01X C Monoclonal antibodies 0.2136 0.2905 0.5041 0.2582 0.3060 0.5641 5,250 7,883 13,133 6,444 7,873 14,317 L01X C02 Rituximab 0.1253 0.0880 0.2133 0.1575 0.0946 0.2521 2,854 2,003 4,857 3,648 2,190 5,838 L01X C03 Trastuzumab 0.0645 0.0823 0.1468 0.0801 0.0818 0.1619 1,835 2,342 4,177 2,320 2,366 4,686 L01X C06 Cetuximab 0.0138 0.0295 0.0433 0.0126 0.0217 0.0343 196 420 616 183 315 497 85 L01X C07 Bevacizumab 0.0074 0.0789 0.0864 0.0071 0.0755 0.0826 283 2,995 3,278 275 2,913 3,187 L01X C08 Panitumumab 0.0022 0.0032 0.0054 0.0005 0.0023 0.0028 83 123 205 19 90 109 L01X C12 Brentuximab vedotin <0.0001 0.0001 0.0002 - 0.0003 0.0003 ------L01X C13 Pertuzumab - 0.0070 0.0070 0.0002 0.0205 0.0207 ------L01X C14 Trastuzumab 0.0004 0.0014 0.0017 0.0001 0.0023 0.0024 ------emtansine L01X C15 Obinutuzumab - - - - 0.0019 0.0019 ------L01X C18 Pembrolizumab - - - - 0.0051 0.0051 ------

L01X D Sensitizers used in - - - <0.0001 - <0.0001 ------photodynamic/ radiation therapy L01X D04 Aminolevulinic acid - - - <0.0001 - <0.0001 ------

L01X E Protein kinase 6.5592 3.6901 10.2493 8.7960 3.8661 12.6621 27,461 32,738 60,199 36,862 38,168 75,030 inhibitors L01X E01 Imatinib 1.4285 0.5387 1.9672 3.3478 0.4659 3.8137 1,452 547 1,999 3,461 482 3,942 L01X E02 Gefitinib 0.5146 0.9099 1.4245 0.3174 0.7890 1.1064 837 1,480 2,316 525 1,305 1,830 L01X E03 Erlotinib 0.1384 0.2604 0.3988 0.1093 0.2469 0.3563 563 1,059 1,621 452 1,021 1,473 L01X E04 Sunitinib 0.0114 0.0099 0.0213 0.0066 0.0107 0.0173 124 107 231 72 118 191 L01X E05 Sorafenib 0.1581 0.4554 0.6136 0.1337 0.3887 0.5224 80 231 312 69 201 270

Table 11.6 (continued) ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in total cycle/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

L01X E07 Lapatinib 0.1845 0.3551 0.5396 0.1209 0.4398 0.5608 792 1,525 2,318 528 1,922 2,450 L01X E08 Nilotinib 3.1392 0.2219 3.3611 3.1101 0.1954 3.3055 927 66 993 935 59 993 L01X E09 Temsirolimus - 0.0003 0.0003 - 0.0006 0.0006 - 30 30 - 64 64 L01X E10 Everolimus 0.0031 0.0051 0.0082 0.0040 0.0051 0.0091 3,585 5,790 9,375 4,635 5,865 10,500 L01X E11 Pazopanib 0.9425 0.6188 1.5613 1.6086 0.6525 2.2610 13,410 8,805 22,215 23,280 9,443 32,723 L01X E13 Afatinib 0.0200 0.0460 0.0660 0.0100 0.0611 0.0711 5,691 13,097 18,788 2,905 17,689 20,594 L01X E15 Vemurafenib - 0.0130 0.0130 - 0.0151 0.0151 ------L01X E16 Crizotinib 0.0132 0.2296 0.2427 0.0246 0.3576 0.3822 ------L01X E17 Axitinib 0.0002 0.0016 0.0018 0.0001 0.0016 0.0017 ------L01X E18 Ruxolitinib 0.0003 0.0107 0.0110 0.0008 0.0167 0.0174 ------L01X E21 Regorafenib 0.0052 0.0137 0.0189 0.0021 0.0141 0.0163 ------L01X E27 Ibrutinib - - - - 0.0410 0.0410 ------L01X E28 Ceritinib - - - - 0.1185 0.1185 ------L01X E31 Nintedanib - - - - 0.0031 0.0031 ------L01X E33 Palbociclib - - - - 0.0427 0.0427 ------86 L01X X Other antineoplastic 40.3490 6.8217 47.1707 39.3497 8.8321 48.1818 17,425 4,705 22,130 19,451 5,456 24,907 agents L01X X02 Asparaginase 4.1422 0.4999 4.6420 4.4058 0.6383 5.0441 2,358 285 2,642 2,551 370 2,920 L01X X05 Hydroxycarbamide 35.7026 6.2769 41.9795 34.8467 8.1276 42.9743 9,676 1,701 11,377 9,606 2,240 11,846 L01X X14 Tretinoin 0.0337 0.0096 0.0433 0.0331 0.0125 0.0456 331 94 425 330 125 455 L01X X17 Topotecan <0.0001 0.0001 0.0001 <0.0001 0.0001 0.0001 19 104 123 31 74 105 L01X X19 Irinotecan 0.0174 0.0298 0.0473 0.0519 0.0276 0.0795 641 1,095 1,736 1,940 1,030 2,970 L01X X23 Mitotane 0.4393 - 0.4393 - - - 18 - 18 - - - L01X X27 Arsenic trioxide 0.0041 0.0018 0.0059 0.0010 0.0081 0.0091 112 48 160 26 225 251 L01X X32 Bortezomib 0.0004 0.0002 0.0005 0.0004 0.0002 0.0006 466 198 664 523 296 819 L01X X35 Anagrelide 0.0093 0.0023 0.0117 0.0106 0.0021 0.0128 3,786 954 4,739 4,404 875 5,279 L01X X38 Vorinostat - 0.0011 0.0011 ------L01X X41 Eribulin <0.0001 0.0001 0.0001 <0.0001 0.0001 0.0001 19 228 247 41 221 262 L01X X44 Aflibercept - - - 0.0001 0.0020 0.0021 ------L01X X46 Olaparib - - - - 0.0135 0.0135 ------

Table 11.7 Drugs for endocrine therapy, L02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

L02A Hormones and related agents 0.0618 0.0694 0.1312 0.0614 0.0804 0.1418

L02A B Progestogens 0.0011 0.0061 0.0072 0.0004 0.0100 0.0104 L02A B01 Megestrol 0.0004 0.0061 0.0066 0.0004 0.0100 0.0104 L02A B02 Medroxyprogesterone 0.0007 - 0.0007 - - -

L02A E Gonadotropin releasing 0.0607 0.0633 0.1240 0.0610 0.0704 0.1314 hormone analogues L02A E01 Buserelin - 0.0010 0.0010 <0.0001 0.0011 0.0012 L02A E02 Leuprorelin 0.0508 0.0413 0.0920 0.0529 0.0480 0.1008 L02A E03 Goserelin 0.0076 0.0117 0.0193 0.0061 0.0109 0.0170 L02A E04 Triptorelin 0.0023 0.0093 0.0117 0.0019 0.0104 0.0124

L02B Hormone antagonists and 0.2949 0.1318 0.4267 0.2968 0.1478 0.4446 related agents

L02B A Anti-estrogens 0.2316 0.0898 0.3214 0.2320 0.0988 0.3307 L02B A01 Tamoxifen 0.2315 0.0890 0.3205 0.2319 0.0974 0.3294 L02B A03 Fulvestrant <0.0001 0.0009 0.0009 <0.0001 0.0013 0.0014

L02B B Anti-androgens 0.0160 0.0077 0.0237 0.0195 0.0094 0.0289 L02B B01 Flutamide 0.0002 0.0008 0.0010 0.0003 0.0013 0.0015 L02B B03 Bicalutamide 0.0158 0.0069 0.0227 0.0192 0.0080 0.0272 L02B B04 Enzalutamide - - - - 0.0001 0.0001

L02B G Aromatase inhibitors 0.0460 0.0326 0.0786 0.0449 0.0378 0.0827 L02B G03 Anastrozole 0.0217 0.0135 0.0352 0.0068 0.0150 0.0219 L02B G04 Letrozole 0.0195 0.0161 0.0356 0.0327 0.0191 0.0518 L02B G06 Exemestane 0.0049 0.0030 0.0078 0.0053 0.0036 0.0090

L02B X Other hormone antagonists 0.0012 0.0017 0.0030 0.0004 0.0019 0.0023 and related agents L02B X02 Degarelix 0.0009 0.0005 0.0014 0.0002 0.0006 0.0008 L02B X03 Abiraterone 0.0003 0.0013 0.0016 0.0003 0.0012 0.0015

Table 11.8 Immunostimulants, L03 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

L03A Immunostimulants 0.0209 0.0075 0.0284 0.0150 0.0077 0.0227

L03A A Colony stimulating factors 0.0071 0.0043 0.0114 0.0057 0.0052 0.0108 L03A A02 Filgrastim 0.0066 0.0014 0.0080 0.0053 0.0017 0.0070 L03A A10 Lenograstim 0.0002 0.0002 0.0004 0.0002 0.0001 0.0003 L03A A13 Pegfilgrastim 0.0003 0.0027 0.0030 0.0002 0.0033 0.0035

L03A B Interferons 0.0137 0.0032 0.0169 0.0093 0.0025 0.0119 L03A B04 Interferon alfa-2a 0.0002 <0.0001 0.0002 0.0001 <0.0001 0.0001 L03A B05 Interferon alfa-2b 0.0008 <0.0001 0.0008 0.0013 0.0001 0.0014 L03A B07 Interferon beta-1a 0.0063 0.0011 0.0074 0.0043 0.0008 0.0051 L03A B08 Interferon beta-1b 0.0004 0.0001 0.0005 <0.0001 <0.0001 0.0001 L03A B10 Peginterferon alfa-2b 0.0013 0.0008 0.0020 0.0004 0.0001 0.0005 L03A B11 Peginterferon alfa-2a 0.0047 0.0013 0.0060 0.0033 0.0014 0.0047

L03A X Other immunostimulants 0.0001 <0.0001 0.0001 <0.0001 <0.0001 <0.0001 L03A X03 BCG vaccine 0.0001 - 0.0001 - - - L03A X16 Plerixafor - <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

Table 11.9 Immunosuppresants, L04 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

L04A Immunosuppressants 0.3728 0.1602 0.5330 0.4721 0.1740 0.6460

L04A A Selective immunosuppressants 0.0753 0.0286 0.1039 0.1012 0.0291 0.1303 L04A A03 Antilymphocyte 0.0001 <0.0001 0.0001 0.0002 <0.0001 0.0002 immunoglobulin (horse) L04A A04 Antithymocyte <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 immunoglobulin (rabbit) L04A A06 Mycophenolic acid 0.0373 0.0170 0.0543 0.0404 0.0181 0.0584 L04A A10 Sirolimus 0.0003 0.0001 0.0005 0.0003 0.0001 0.0004 L04A A13 Leflunomide 0.0330 0.0094 0.0424 0.0580 0.0071 0.0651 L04A A18 Everolimus 0.0039 0.0016 0.0055 0.0017 0.0023 0.0040 L04A A23 Natalizumab <0.0001 <0.0001 <0.0001 - <0.0001 <0.0001 L04A A26 Belimumab 0.0001 0.0001 0.0002 0.0002 <0.0001 0.0002 L04A A27 Fingolimod 0.0004 0.0001 0.0005 0.0002 0.0002 0.0004 L04A A29 Tofacitinib 0.0002 0.0003 0.0005 0.0004 0.0012 0.0015

L04A B Tumor necrosis factor alpha 0.0064 0.0075 0.0140 0.0054 0.0099 0.0153 (TNF-α) inhibitors L04A B01 Etanercept 0.0014 0.0016 0.0031 0.0012 0.0021 0.0033 L04A B02 Infliximab 0.0020 0.0028 0.0049 0.0019 0.0039 0.0058 L04A B04 Adalimumab 0.0025 0.0016 0.0041 0.0019 0.0019 0.0038 L04A B05 Certolizumab pegol - 0.0003 0.0003 - 0.0005 0.0005 L04A B06 Golimumab 0.0005 0.0011 0.0016 0.0004 0.0015 0.0019

L04A C Interleukin inhibitors 0.0017 0.0028 0.0045 0.0013 0.0037 0.0050 L04A C02 Basiliximab <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 L04A C05 Ustekinumab 0.0012 0.0014 0.0026 0.0009 0.0013 0.0022 L04A C07 Tocilizumab 0.0005 0.0014 0.0019 0.0004 0.0019 0.0023 L04A C10 Secukinumab - - - - 0.0005 0.0005

L04A D Calcineurin inhibitors 0.0491 0.0072 0.0562 0.0451 0.0086 0.0537 L04A D01 Ciclosporin 0.0344 0.0042 0.0387 0.0313 0.0044 0.0357 L04A D02 Tacrolimus 0.0146 0.0029 0.0176 0.0139 0.0041 0.0180

L04A X Other immunosuppressants 0.2402 0.1141 0.3543 0.3190 0.1227 0.4418 L04A X01 Azathioprine 0.1135 0.0195 0.1329 0.1034 0.0189 0.1223 L04A X02 Thalidomide 0.0092 0.0031 0.0123 0.0029 0.0044 0.0072 L04A X03 Methotrexate 0.1175 0.0913 0.2087 0.2127 0.0989 0.3116 L04A X04 Lenalidomide 0.0001 0.0002 0.0003 0.0001 0.0006 0.0006 L04A X06 Pomalidomide - - - - <0.0001 <0.0001

Utilisation of antineoplastic agents, targeted therapy and endocrine 11.2 therapy Ros Suzanna Ahmad Bustaman, Prathepamalar Yehgambaram, Tan Chih Kiang, Nik Nuradlina Nik Adnan, Lee Mei Wah

Globocan reported 18.1 million new cancer cases and 9.6 million cancer deaths in 2018 worldwide.1 About 48.4% of the new cancer cases happened in Asia.1 In Malaysia, a total number of 106,262 new cancer cases were diagnosed during the period of 2014 to 2018.1 The five commonest cancer were breast (17.3%), colorectal (13.7%), lung (10.7%), nasopharyx (4.8%) and liver (4.4%).

The top five antineoplastic agents being used in Malaysia from 2015 to 2016 were capecitabine, 5- fluorouracil, cyclophosphamide, gemcitabine and carboplatin. The antineoplastic agents with the highest increment in use in public facilities were irinotecan (198.3%) and oxaliplatin (91.0%). The usage increment of irinotecan and oxaliplatin is in line with previous years, which had shown increased usage since 2011.2 Both the agents are mainly used in colorectal cancer as well as other solid tumours of the gastrointestinal tract.

The highest usage increment in private facilities was medicine with tegafur combinations with a 157.6% increment from 2015 to 2016. This is mainly due to the introduction of tegafur combinations in 2015, with very little or no usage prior to that. Furthermore, it may be preferred by patients due to its convenient oral administration route.

In short, there has been an increase in antineoplastic agents used over the years in line with an increased in number of new cancer cases diagnosed.

Targeted therapy

In general, there had been a rise in the use of targeted therapy (21%) and monoclonal antibodies (9%) in 2016 compared to 2015, both in public and private health sectors in Malaysia. The five commonly used targeted therapy in oncology specialty for the year 2015 and 2016 were imatinib, pazopanib, gefitinib, lapatinib and sorafenib. Imatinib remained as the targeted therapy with the highest use because it is being prescribed for both gastrointestinal stromal tumour and chronic myeloid leukemia.

Pazopanib was listed in Ministry of Health Malaysia Medicines Formulary (MoHMF) in 2013 as it had showed to increase progression-free survival in patients with metastatic renal cell carcinoma in two phase III randomized controlled trials.3,4 Thus, the usage of this drug has gradually increased over the years, with an increase of 44.8% from 2015 to 2016. Afatinib was approved by Food and Drug Administration (FDA) in 2013 for first line treatment of patients with metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 mutation.5 This resulted in usage increment from 2015 to 2016, mainly in private facilities.

Endocrine therapy

Tamoxifen remained the top hormonal therapy used in breast cancer and its usage was stable between 2015 and 2016. The use of aromatase inhibitors namely letrozole, anastrozole and exemestane has been increasing over the years.

The landscape for hormonal treatment in prostate cancer has remained in status quo as demonstrated in the usage value.

Immunostimulants

Overall, the use of colony stimulating factors had reduced in 2016 compared to 2015. This could be due to more patients are using targeted therapy which has minimal risk of neutropenia compared to standard chemotherapy. The commonest agent used was filgrastim.

Antiemetics

There was an increase of serotonin (5HT3) antagonist usage by 28.1% in both public and private hospitals in 2016 (Table 4.4). The usage of granisetron was higher than ondansetron. Granisetron has a longer half- life and more effective than ondansetron in the prevention of delayed nausea and vomiting associated with chemotherapy.6 The use of aprepitant was reduced by 50.0% in public hospitals.

Utilisation of immunosuppressive agents in rheumatology 11.3 Gun Suk Chyn, Mollyza Mohd Zain, Liza Mohd Isa, Chong Hwee Cheng, Siti Rabiatul Adawiyah

The immunosuppressive agents commonly used in Malaysia include selective immunosuppressants (mycophenolic acid, leflunomide, belimumab and tofacitinib), tumour necrosis factor alpha (TNF-) inhibitors (etanercept, infliximab, adalimumab, golimumab and certolizumab pegol), interleukin inhibitors (tocilizumab and secukinumab) and other immunosuppressants (azathioprine, methotrexate, hydroxychloroquine and sulfasalazine).

The overall usage of immunosuppressants in 2015 and 2016 showed an increasing trend from 0.5330 DDD/1,000 inhabitants/day to 0.6460 DDD/1,000 inhabitants/day, indicating a 21.2% rise (Table 11.9). Despite this, the use of immunosuppressive agents in Malaysia was still much lower in comparison to Finland due to a limited availability of immunosuppressive agents.1

Within the group of selective immunosuppressants, mycophenolic acid had a DDD/1,000 inhabitants/day of 0.0543 in 2015 which had increased to 0.0584 in 2016. Public sector usage was higher than the private sector. This increment was likely contributed by non-renal transplant indications such as lupus nephritis, extra-renal lupus and other autoimmune diseases. The use of leflunomide was 0.0424 DDD/1,000 inhabitants/day in 2015 and 0.0651 DDD/1,000 inhabitants/day in 2016. Leflunomide use in public sector was 3.5 times higher compared to private sector in 2015 and the gap widened further to eight times in 2016. Tofacitinib use was low when first introduced in 2015 with DDD/1,000 inhabitants/day of 0.0005 but had increased three folds in 2016 with DDD/1,000 inhabitants/day of 0.0015 (Table 11.9).

Usage of TNF- inhibitors remained low in 2015 and 2016 due to the high cost. There was a 15.6% reduction in TNF- inhibitors use in the public sector with DDD/1,000 inhabitants/day of 0.0064 to 0.0054. On the other hand, the use in private sector was increased by 32.0% with DDD/1,000 inhabitants/day of 0.0075 to 0.0099. The commonest used TNF- inhibitors was infliximab, followed by adalimumab, etanercept and golimumab. Certolizumab was only used in the private sector as it was not registered in the MoHMF.

Tocilizumab was the only interleukin inhibitor used in 2015 with DDD/1,000 inhabitants/day of 0.0019. Its use remained low in the public sector but there was an increased use of 35.7% in the private sector with DDD/ 1,000 inhabitants/day of 0.0014 in 2015 to 0.0019 in 2016. Secukinumab was introduced in 2016 and was used only in the private sector with DDD/1,000 inhabitants/day of 0.0005.

There was a rise of 81.0% in the use of methotrexate in the public sector compared to 8.3% in the private sector. In contrast, there was a reduction in the usage of hydroxychloroquine (Table 14.3), sulfasalazine (Table 4.7) and azathioprine by 18.5%, 2.6% and 8.0%, respectively, over the two years.

REFERENCES

1. Bray, F.; Ferlay, J.; Soerjomataram, I.; et al. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer J. Clin. 2018, 68, 394–424. 2. Malaysian Statistics on Medicines 2011-2014; Pharmaceutical Services Division, Ministry of Health Malaysia: Kuala Lumpur, 2017. 3. Sternberg, C. N.; Davis, I. D.; Mardiak, J.; et al. Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial. J. Clin. Oncol. 2010, 28(6), 1061–1068. 4. Motzer, R. J.; Hutson, T. E.; Cella, D.; et al. Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma. N. Engl. J. Med. 2013, 369, 722–731. 5. Sequist, L. V.; Yang, J. C.; Yamamoto, N.; et al. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients with Metastatic Lung Adenocarcinoma with EGFR Mutations. J. Clin. Oncol. 2013, 31(27), 3327‐3334. 6. Stewart, L.; Crawford, S. M.; Taylor, P. A. The Comparative Effectiveness of Ondansetron and Granisetron in a Once Daily Dosage in the Prevention of Nausea and Vomiting Caused by Cisplatin: a Double-Blind Clinical Trial. The Pharmaceutical Journal 2000, 265(7104), 59-62.

12 Musculo-Skeletal System

Statistics on medicines for musculo-skeletal system 12.1

Table 12.1 Statistics by therapeutic groups for musculo-skeletal system, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

M Musculo-skeletal system 3.7443 13.8012 17.5455 3.2830 11.9622 15.2452

M01 Antiinflammatory and 2.3547 11.2517 13.6065 2.0019 9.6440 11.6460 antirheumatic products M03 Muscle relaxants 0.1673 1.0697 1.2370 0.1293 0.9284 1.0578 M04 Antigout preparations 0.9282 0.9346 1.8628 0.9175 0.9125 1.8300 M05 Drugs for treatment of bone 0.2941 0.5452 0.8393 0.2341 0.4773 0.7114 diseases

Table 12.2 Statistics by therapeutic groups for musculo-skeletal system, in public and private sector (Utilisation in DDD/inhabitants/year) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

M Musculo-skeletal system 1.3667 5.0375 6.4041 1.2016 4.3782 5.5797

M01 Antiinflammatory and 0.8595 4.1069 4.9664 0.7327 3.5297 4.2624 antirheumatic products M03 Muscle relaxants 0.0611 0.3904 0.4515 0.0473 0.3398 0.3871 M04 Antigout preparations 0.3388 0.3411 0.6799 0.3358 0.3340 0.6698 M05 Drugs for treatment of bone 0.1073 0.1990 0.3063 0.0857 0.1747 0.2604 diseases

Table 12.3 Antiinflammatory and antirheumatic products, M01 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

M01A Antiinflammatory and 2.3540 11.2515 13.6054 2.0012 9.6440 11.6452 0.8592 4.1068 4.9660 0.7324 3.5297 4.2622 antirheumatic products, non-steroids

M01A B Acetic acid derivatives 1.0676 3.3875 4.4551 0.7494 2.2977 3.0471 0.3897 1.2364 1.6261 0.2743 0.8409 1.1152 and related substances M01A B01 Indometacin 0.0487 0.0398 0.0885 0.0265 0.0276 0.0541 0.0178 0.0145 0.0323 0.0097 0.0101 0.0198 M01A B05 Diclofenac 1.0173 3.3311 4.3484 0.7215 2.2701 2.9916 0.3713 1.2159 1.5872 0.2641 0.8308 1.0949 M01A B11 Acemetacin - 0.0165 0.0165 - - - - 0.0060 0.0060 - - - M01A B15 Ketorolac 0.0016 <0.0001 0.0017 0.0014 <0.0001 0.0014 0.0006 <0.0001 0.0006 0.0005 <0.0001 0.0005

M01A C Oxicams 0.0477 1.4343 1.4820 0.0329 1.2173 1.2501 0.0174 0.5235 0.5409 0.0120 0.4455 0.4575 M01A C01 Piroxicam 0.0002 0.3588 0.3590 <0.0001 0.4823 0.4823 0.0001 0.1310 0.1310 <0.0001 0.1765 0.1765 M01A C02 Tenoxicam - 0.0253 0.0253 - 0.0105 0.0105 - 0.0092 0.0092 - 0.0038 0.0038 92 M01A C06 Meloxicam 0.0475 1.0501 1.0977 0.0328 0.7246 0.7574 0.0173 0.3833 0.4006 0.0120 0.2652 0.2772

M01A E Propionic acid 0.1400 2.0949 2.2349 0.0974 2.0922 2.1896 0.0511 0.7646 0.8157 0.0357 0.7658 0.8014 derivatives M01A E01 Ibuprofen 0.0895 0.5848 0.6744 0.0735 0.4986 0.5721 0.0327 0.2135 0.2462 0.0269 0.1825 0.2094 M01A E02 Naproxen 0.0505 1.3798 1.4303 0.0239 1.4792 1.5031 0.0184 0.5036 0.5221 0.0088 0.5414 0.5501 M01A E17 Dexketoprofen - 0.0051 0.0051 - 0.0040 0.0040 - 0.0019 0.0019 - 0.0015 0.0015 M01A E52 Naproxen and - 0.1251 0.1251 - 0.1104 0.1104 - 0.0457 0.0457 - 0.0404 0.0404 esomeprazole

M01A G Fenamates 0.6041 1.8817 2.4857 0.5302 1.5307 2.0609 0.2205 0.6868 0.9073 0.1941 0.5602 0.7543 M01A G01 Mefenamic acid 0.6041 1.8817 2.4857 0.5302 1.5307 2.0609 0.2205 0.6868 0.9073 0.1941 0.5602 0.7543

M01A H Coxibs 0.4946 2.4531 2.9477 0.5913 2.5062 3.0975 0.1805 0.8954 1.0759 0.2164 0.9173 1.1337 M01A H01 Celecoxib 0.3579 1.0148 1.3727 0.4496 1.0608 1.5103 0.1306 0.3704 0.5010 0.1645 0.3882 0.5528 M01A H04 Parecoxib 0.0029 0.0422 0.0451 0.0052 0.0475 0.0526 0.0011 0.0154 0.0164 0.0019 0.0174 0.0193 M01A H05 Etoricoxib 0.1338 1.3962 1.5299 0.1366 1.3979 1.5345 0.0488 0.5096 0.5584 0.0500 0.5116 0.5616

Table 12.3 (continued) ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

M01C Specific antirheumatic 0.0008 0.0003 0.0010 0.0007 <0.0001 0.0007 0.0003 0.0001 0.0004 0.0003 <0.0001 0.0003 agents

M01C C Penicillamine and 0.0008 0.0003 0.0010 0.0007 <0.0001 0.0007 0.0003 0.0001 0.0004 0.0003 <0.0001 0.0003 similar agents M01C C01 Penicillamine 0.0008 0.0003 0.0010 0.0007 <0.0001 0.0007 0.0003 0.0001 0.0004 0.0003 <0.0001 0.0003

Table 12.4 Muscle relaxants, M03 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

M03B Muscle relaxants, 0.1673 1.0697 1.2370 0.1293 0.9284 1.0578 0.0611 0.3904 0.4515 0.0473 0.3398 0.3871 93

centrally acting agents

M03B B Oxazol, thiazine, and - 0.1421 0.1421 - 0.1221 0.1221 - 0.0519 0.0519 - 0.0447 0.0447 triazine derivatives M03B B03 Chlorzoxazone - 0.1421 0.1421 - 0.1221 0.1221 - 0.0519 0.0519 - 0.0447 0.0447

M03B C Ethers, chemically 0.0105 0.7499 0.7604 0.0045 0.6261 0.6307 0.0038 0.2737 0.2776 0.0017 0.2292 0.2308 close to antihistamines M03B C01 Orphenadrine (citrate) 0.0102 0.0593 0.0694 0.0044 0.0554 0.0598 0.0037 0.0216 0.0253 0.0016 0.0203 0.0219 M03B C51 Orphenadrine, 0.0003 0.6906 0.6910 0.0001 0.5707 0.5709 0.0001 0.2521 0.2522 <0.0001 0.2089 0.2089 combinations

M03B X Other centrally acting 0.1568 0.1776 0.3344 0.1248 0.1802 0.3050 0.0572 0.0648 0.1221 0.0457 0.0660 0.1116 agents M03B X01 Baclofen 0.1024 0.0064 0.1088 0.1017 0.0050 0.1067 0.0374 0.0023 0.0397 0.0372 0.0018 0.0391 M03B X09 Eperisone 0.0544 0.1712 0.2256 0.0231 0.1752 0.1983 0.0198 0.0625 0.0823 0.0084 0.0641 0.0726

Table 12.5 Antigout preparations, M04 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/per inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

M04A Antigout preparations 0.9282 0.9346 1.8628 0.9175 0.9125 1.8300 0.3388 0.3411 0.6799 0.3358 0.3340 0.6698

M04A A Preparations inhibiting 0.8154 0.4365 1.2518 0.7698 0.4020 1.1718 0.2976 0.1593 0.4569 0.2817 0.1471 0.4289 uric acid production M04A A01 Allopurinol 0.8146 0.4273 1.2420 0.7691 0.3942 1.1633 0.2973 0.1560 0.4533 0.2815 0.1443 0.4258 M04A A03 Febuxostat 0.0007 - 0.0007 0.0007 0.0001 0.0009 0.0003 - 0.0003 0.0003 <0.0001 0.0003 M04A A51 Allopurinol, - 0.0092 0.0092 - 0.0076 0.0076 - 0.0033 0.0033 - 0.0028 0.0028 combinations

M04A B Preparations 0.0015 0.0056 0.0071 0.0022 0.0030 0.0052 0.0005 0.0020 0.0026 0.0008 0.0011 0.0019 increasing uric acid excretion M04A B01 Probenecid 0.0015 0.0056 0.0071 0.0022 0.0030 0.0052 0.0005 0.0020 0.0026 0.0008 0.0011 0.0019

M04A C Preparations with no 0.1114 0.4926 0.6040 0.1456 0.5074 0.6530 0.0406 0.1798 0.2204 0.0533 0.1857 0.2390 94 effect on uric acid metabolism M04A C01 Colchicine 0.1114 0.4926 0.6040 0.1456 0.5074 0.6530 0.0406 0.1798 0.2204 0.0533 0.1857 0.2390

Table 12.6 Drugs for treatment of bone diseases, M05 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/per inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

M05B Drugs affecting bone 0.2941 0.5452 0.8393 0.2341 0.4773 0.7114 0.1073 0.1990 0.3063 0.0857 0.1747 0.2604 structure and mineralization

M05B A Bisphosphonates 0.0967 0.1226 0.2193 0.0974 0.1277 0.2251 0.0353 0.0448 0.0801 0.0357 0.0467 0.0824 M05B A02 Clodronic acid 0.0010 0.0007 0.0017 0.0006 0.0005 0.0011 0.0004 0.0002 0.0006 0.0002 0.0002 0.0004 M05B A03 Pamidronic acid 0.0002 <0.0001 0.0002 0.0002 0.0001 0.0003 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 M05B A04 Alendronic acid 0.0768 0.0651 0.1420 0.0737 0.0652 0.1390 0.0280 0.0238 0.0518 0.0270 0.0239 0.0509 M05B A06 Ibandronic acid 0.0180 0.0530 0.0710 0.0225 0.0576 0.0801 0.0066 0.0194 0.0259 0.0082 0.0211 0.0293 M05B A07 Risedronic acid 0.0005 0.0035 0.0040 - 0.0042 0.0042 0.0002 0.0013 0.0015 - 0.0015 0.0015 M05B A08 Zoledronic acid 0.0003 0.0003 0.0005 0.0004 0.0002 0.0005 0.0001 0.0001 0.0002 0.0001 0.0001 0.0002

M05B B Bisphosphonates, 0.1455 0.1516 0.2971 0.0918 0.1375 0.2293 0.0531 0.0553 0.1085 0.0336 0.0503 0.0839 combinations M05B B03 Alendronic acid and 0.1455 0.1516 0.2971 0.0918 0.1375 0.2293 0.0531 0.0553 0.1085 0.0336 0.0503 0.0839 95 colecalciferol

M05B X Other drugs affecting 0.0519 0.2709 0.3228 0.0449 0.2121 0.2569 0.0189 0.0989 0.1178 0.0164 0.0776 0.0940 bone structure and mineralization M05B X03 Strontium ranelate 0.0129 0.1274 0.1403 0.0121 0.1107 0.1228 0.0047 0.0465 0.0512 0.0044 0.0405 0.0450 M05B X04 Denosumab 0.0390 0.1435 0.1825 0.0328 0.1013 0.1341 0.0142 0.0524 0.0666 0.0120 0.0371 0.0491

13 Nervous System

Statistics on medicines for nervous system 13.1

Table 13.1 Statistics by therapeutic groups for nervous system, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

N Nervous system 12.1210 9.6454 21.7664 11.4169 9.2311 20.6480

N02 Analgesics 4.1205 5.5553 9.6759 3.6324 5.3432 8.9757 N03 Antiepileptics 1.8070 0.3652 2.1723 1.6813 0.3884 2.0697 N04 Anti-parkinson drugs 0.7606 0.1318 0.8925 0.6800 0.1455 0.8255 N05 Psycholeptics 2.8144 1.4146 4.2290 2.7182 1.2788 3.9970 N06 Psychoanaleptics 1.4205 1.0645 2.4850 1.3971 0.9546 2.3517 N07 Other nervous system drugs 1.1979 1.1139 2.3118 1.3078 1.1206 2.4284

Table 13.2 Analgesics, N02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

N02A Opioids 0.2777 0.3482 0.6259 0.3634 0.2641 0.6275

N02A A Natural opium alkaloids 0.0565 0.0136 0.0700 0.0583 0.0123 0.0706 N02A A01 Morphine 0.0366 0.0032 0.0398 0.0428 0.0036 0.0464 N02A A05 Oxycodone 0.0089 0.0045 0.0134 0.0066 0.0048 0.0115 N02A A08 Dihydrocodeine 0.0078 0.0036 0.0114 0.0073 0.0015 0.0089 N02A A55 Oxycodone and naloxone 0.0032 0.0023 0.0054 0.0016 0.0023 0.0039

N02A B Phenylpiperidine derivatives 0.0056 0.0096 0.0152 0.0058 0.0100 0.0159 N02A B02 Pethidine 0.0035 0.0088 0.0123 0.0030 0.0093 0.0123 N02A B03 Fentanyl 0.0020 0.0008 0.0029 0.0029 0.0007 0.0036

N02A E Oripavine derivatives <0.0001 0.0001 0.0001 <0.0001 <0.0001 0.0001 N02A E01 Buprenorphine <0.0001 0.0001 0.0001 <0.0001 <0.0001 0.0001

N02A F Morphinan derivatives 0.0008 0.0002 0.0010 0.0007 0.0002 0.0009 N02A F02 Nalbuphine 0.0008 0.0002 0.0010 0.0007 0.0002 0.0009

N02A J Opioids in combination with 0.0028 0.1804 0.1833 0.0026 0.1425 0.1451 non-opioid analgesics N02A J06 Codeine and paracetamol - 0.0989 0.0989 - 0.0866 0.0866 N02A J13 Tramadol and paracetamol 0.0028 0.0815 0.0843 0.0026 0.0559 0.0584

N02A X Other opioids 0.2120 0.1443 0.3563 0.2960 0.0990 0.3950 N02A X02 Tramadol 0.2120 0.1443 0.3563 0.2960 0.0990 0.3950

N02B Other analgesics and 3.8194 5.1185 8.9379 3.2542 5.0033 8.2575 antipyretics

N02B A Salicylic acid and derivatives - 0.0131 0.0131 - 0.0255 0.0255 N02B A01 Acetylsalicylic acid - 0.0096 0.0096 - 0.0223 0.0223 N02B A51 Acetylsalicylic acid, - 0.0035 0.0035 - 0.0032 0.0032 combinations excluding psycholeptics

N02B E Anilides 3.8194 5.1054 8.9248 3.2542 4.9777 8.2320 N02B E01 Paracetamol 3.8194 4.8978 8.7173 3.2542 4.8738 8.1280 N02B E51 Paracetamol, combinations - 0.1834 0.1834 - 0.1021 0.1021 excluding psycholeptics N02B E71 Paracetamol, combinations - 0.0241 0.0241 - 0.0019 0.0019 with psycholeptics

N02C Antimigraine preparations 0.0234 0.0887 0.1121 0.0148 0.0759 0.0907

N02C A Ergot alkaloids 0.0001 0.0747 0.0748 0.0003 0.0623 0.0626 N02C A52 Ergotamine, combinations 0.0001 0.0747 0.0748 0.0003 0.0623 0.0626 excluding psycholeptics

N02C C Selective serotonin (5HT1) 0.0090 0.0081 0.0170 0.0051 0.0075 0.0126 agonists N02C C01 Sumatriptan 0.0090 0.0081 0.0170 0.0051 0.0075 0.0126

N02C X Other antimigraine 0.0143 0.0059 0.0203 0.0095 0.0061 0.0156 preparations N02C X01 Pizotifen 0.0133 0.0059 0.0192 0.0091 0.0061 0.0152 N02C X02 Clonidine 0.0011 - 0.0011 0.0004 - 0.0004

Table 13.3 Antiepileptics, N03 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

N03A Antiepileptics 1.8070 0.3652 2.1723 1.6813 0.3884 2.0697

N03A A Barbiturates and derivatives 0.0572 0.0167 0.0739 0.0483 0.0203 0.0686 N03A A02 Phenobarbital 0.0570 0.0166 0.0736 0.0480 0.0201 0.0681 N03A A03 Primidone 0.0002 0.0001 0.0003 0.0003 0.0002 0.0005

N03A B Hydantoin derivatives 0.4433 0.0356 0.4789 0.3807 0.0338 0.4145 N03A B02 Phenytoin 0.4433 0.0356 0.4789 0.3807 0.0338 0.4145

N03A E Benzodiazepine derivatives 0.0731 0.0507 0.1238 0.0785 0.0531 0.1316 N03A E01 Clonazepam 0.0731 0.0507 0.1238 0.0785 0.0531 0.1316

N03A F Carboxamide derivatives 0.2574 0.0297 0.2872 0.2214 0.0351 0.2566 N03A F01 Carbamazepine 0.2566 0.0240 0.2806 0.2211 0.0299 0.2510 N03A F02 Oxcarbazepine 0.0008 0.0058 0.0066 0.0003 0.0053 0.0056

N03A G Fatty acid derivatives 0.5660 0.0566 0.6226 0.5223 0.0578 0.5800 N03A G01 Valproic acid 0.5651 0.0563 0.6215 0.5214 0.0576 0.5790 N03A G04 Vigabatrin 0.0009 0.0002 0.0011 0.0009 0.0001 0.0010

N03A X Other antiepileptics 0.4099 0.1760 0.5859 0.4302 0.1883 0.6185 N03A X03 Sultiame - - - <0.0001 - <0.0001 N03A X09 Lamotrigine 0.0699 0.0076 0.0775 0.0655 0.0079 0.0735 N03A X11 Topiramate 0.0218 0.0022 0.0240 0.0256 0.0024 0.0280 N03A X12 Gabapentin 0.0992 0.0377 0.1369 0.1485 0.0355 0.1840 N03A X14 Levetiracetam 0.1844 0.0339 0.2183 0.1469 0.0373 0.1842 N03A X15 Zonisamide 0.0056 0.0026 0.0081 0.0036 0.0033 0.0069 N03A X16 Pregabalin 0.0278 0.0897 0.1174 0.0393 0.0982 0.1375 N03A X17 Stiripentol 0.0001 - 0.0001 - - - N03A X18 Lacosamide 0.0011 0.0023 0.0033 0.0006 0.0028 0.0034 N03A X22 Perampanel 0.0001 0.0001 0.0002 0.0001 0.0009 0.0010

Table 13.4 Anti-parkinson drugs, N04 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

N04A Anticholinergic agents 0.4206 0.0439 0.4645 0.3620 0.0473 0.4092

N04A A Tertiary amines 0.4206 0.0439 0.4645 0.3620 0.0473 0.4092 N04A A01 Trihexyphenidyl 0.4205 0.0439 0.4644 0.3619 0.0473 0.4092 N04A A04 Procyclidine 0.0001 - 0.0001 <0.0001 - <0.0001

N04B Dopaminergic agents 0.3400 0.0880 0.4280 0.3181 0.0982 0.4163

N04B A Dopa and dopa derivatives 0.2178 0.0507 0.2684 0.1964 0.0582 0.2545 N04B A02 Levodopa and decarboxylase 0.2062 0.0454 0.2516 0.1864 0.0523 0.2387 inhibitor N04B A03 Levodopa, decarboxylase 0.0116 0.0053 0.0168 0.0100 0.0059 0.0158 inhibitor and comt inhibitor

N04B B Adamantane derivatives 0.0180 0.0019 0.0199 0.0113 0.0008 0.0121 N04B B01 Amantadine 0.0180 0.0019 0.0199 0.0113 0.0008 0.0121

N04B C Dopamine agonists 0.0344 0.0179 0.0523 0.0312 0.0183 0.0495 N04B C04 Ropinirole 0.0091 0.0058 0.0150 0.0078 0.0060 0.0137 N04B C05 Pramipexole 0.0152 0.0060 0.0213 0.0151 0.0067 0.0218 N04B C08 Piribedil 0.0080 0.0034 0.0114 0.0064 0.0029 0.0093 N04B C09 Rotigotine 0.0020 0.0026 0.0047 0.0019 0.0028 0.0047

N04B D Monoamine oxidase B 0.0581 0.0164 0.0746 0.0649 0.0192 0.0842 inhibitors N04B D01 Selegiline 0.0581 0.0164 0.0746 0.0649 0.0192 0.0842

N04B X Other dopaminergic agents 0.0116 0.0010 0.0127 0.0143 0.0016 0.0159 N04B X02 Entacapone 0.0116 0.0010 0.0127 0.0143 0.0016 0.0159

Table 13.5 Psycholeptics, N05 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

N05A Antipsychotics 2.4468 0.2229 2.6696 2.3639 0.2413 2.6052

N05A A Phenothiazines with aliphatic 0.2043 0.0129 0.2172 0.1503 0.0064 0.1567 side-chain N05A A01 Chlorpromazine 0.2043 0.0129 0.2172 0.1503 0.0064 0.1567

N05A B Phenothiazines with piperazine 0.6185 0.0793 0.6978 0.5168 0.0872 0.6040 structure N05A B02 Fluphenazine 0.5152 0.0069 0.5222 0.4199 0.0054 0.4253 N05A B03 Perphenazine 0.0034 0.0005 0.0039 0.0039 0.0050 0.0090 N05A B04 Prochlorperazine 0.0456 0.0450 0.0906 0.0389 0.0431 0.0820 N05A B06 Trifluoperazine 0.0543 0.0269 0.0811 0.0540 0.0337 0.0877

N05A D Butyrophenone derivatives 0.1567 0.0013 0.1579 0.1345 0.0004 0.1349 N05A D01 Haloperidol 0.1567 0.0013 0.1579 0.1345 0.0004 0.1349

N05A E Indole derivatives 0.0003 0.0013 0.0016 0.0003 0.0013 0.0016 N05A E04 Ziprasidone 0.0003 0.0013 0.0016 0.0003 0.0013 0.0016

N05A F Thioxanthene derivatives 0.1780 0.0175 0.1955 0.1719 0.0150 0.1869 N05A F01 Flupentixol 0.0882 0.0124 0.1007 0.0858 0.0103 0.0961 N05A F05 Zuclopenthixol 0.0898 0.0051 0.0949 0.0861 0.0047 0.0908

Table 13.5 (continued) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

N05A H Diazepines, oxazepines, 0.6036 0.0449 0.6485 0.5141 0.0548 0.5689 thiazepines and oxepines N05A H02 Clozapine 0.1126 0.0014 0.1140 0.0848 0.0022 0.0870 N05A H03 Olanzapine 0.3781 0.0228 0.4008 0.2988 0.0275 0.3262 N05A H04 Quetiapine 0.1096 0.0179 0.1275 0.1282 0.0218 0.1500 N05A H05 Asenapine 0.0033 0.0028 0.0061 0.0023 0.0033 0.0056

N05A L Benzamides 0.1620 0.0123 0.1742 0.1893 0.0101 0.1994 N05A L01 Sulpiride 0.1053 0.0057 0.1110 0.1276 0.0050 0.1326 N05A L05 Amisulpride 0.0567 0.0065 0.0632 0.0616 0.0052 0.0668

N05A N Lithium 0.0627 0.0078 0.0705 0.0786 0.0161 0.0947 N05A N01 Lithium 0.0627 0.0078 0.0705 0.0786 0.0161 0.0947

N05A X Other antipsychotics 0.4607 0.0455 0.5062 0.6082 0.0500 0.6582 N05A X08 Risperidone 0.3134 0.0322 0.3455 0.4349 0.0335 0.4684 N05A X12 Aripiprazole 0.0964 0.0063 0.1027 0.1007 0.0096 0.1103 N05A X13 Paliperidone 0.0510 0.0070 0.0581 0.0725 0.0069 0.0794

N05B Anxiolytics 0.2441 0.9257 1.1698 0.1998 0.7976 0.9975

N05B A Benzodiazepine derivatives 0.2098 0.7837 0.9935 0.1786 0.5890 0.7676 N05B A01 Diazepam 0.0519 0.1847 0.2366 0.0351 0.2552 0.2903 N05B A06 Lorazepam 0.0508 0.0584 0.1092 0.0768 0.0710 0.1478 N05B A08 Bromazepam 0.0005 0.0268 0.0273 0.0007 0.0237 0.0244 N05B A09 Clobazam 0.0273 0.0364 0.0637 0.0163 0.0376 0.0539 N05B A12 Alprazolam 0.0794 0.4773 0.5567 0.0496 0.2015 0.2511

N05B B Diphenylmethane derivatives 0.0343 0.1421 0.1763 0.0213 0.2086 0.2299 N05B B01 Hydroxyzine 0.0343 0.1421 0.1763 0.0213 0.2086 0.2299

N05C Hypnotics and sedatives 0.1236 0.2660 0.3896 0.1544 0.2398 0.3943

N05C D Benzodiazepine derivatives 0.0670 0.0979 0.1648 0.0753 0.0583 0.1335 N05C D02 Nitrazepam 0.0046 0.0186 0.0232 0.0025 0.0004 0.0029 N05C D05 Triazolam - 0.0467 0.0467 - 0.0241 0.0241 N05C D08 Midazolam 0.0624 0.0325 0.0950 0.0728 0.0337 0.1065

N05C F Benzodiazepine related drugs 0.0557 0.1680 0.2238 0.0700 0.1815 0.2515 N05C F01 Zopiclone - 0.0529 0.0529 - 0.0581 0.0581 N05C F02 Zolpidem 0.0557 0.1152 0.1709 0.0700 0.1234 0.1934

N05C H Melatonin receptor agonists - - - 0.0084 - 0.0084 N05C H01 Melatonin - - - 0.0084 - 0.0084

N05C M Other hypnotics and sedatives 0.0008 0.0001 0.0009 0.0007 0.0001 0.0008 N05C M18 Dexmedetomidine 0.0008 0.0001 0.0009 0.0007 0.0001 0.0008

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Table 13.6 Psychoanaleptics, N06 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

N06A Antidepressants 1.2485 0.8502 2.0988 1.2135 0.7492 1.9627

N06A A Non-selective monoamine 0.1456 0.0824 0.2281 0.1158 0.0765 0.1924 reuptake inhibitors N06A A02 Imipramine 0.0166 0.0114 0.0279 0.0081 0.0080 0.0161 N06A A04 Clomipramine 0.0128 0.0050 0.0178 0.0053 0.0046 0.0099 N06A A09 Amitriptyline 0.0924 0.0519 0.1443 0.0846 0.0504 0.1350 N06A A10 Nortriptyline 0.0004 - 0.0004 0.0001 - 0.0001 N06A A16 Dosulepin 0.0235 0.0141 0.0376 0.0176 0.0136 0.0312

N06A B Selective serotonin reuptake 0.9764 0.5817 1.5581 0.9663 0.4393 1.4055 inhibitors N06A B03 Fluoxetine 0.1543 0.1231 0.2775 0.0849 0.0464 0.1313 N06A B04 Citalopram - 0.0060 0.0060 - 0.0044 0.0044 N06A B05 Paroxetine 0.0019 0.0295 0.0313 0.0008 0.0246 0.0254 N06A B06 Sertraline 0.3344 0.0766 0.4111 0.2495 0.0503 0.2998 N06A B08 Fluvoxamine 0.2778 0.0432 0.3210 0.3769 0.0399 0.4168 N06A B10 Escitalopram 0.2080 0.3032 0.5112 0.2541 0.2736 0.5277

N06A G Monoamine oxidase A 0.0050 0.0005 0.0054 0.0041 0.0005 0.0046 inhibitors N06A G02 Moclobemide 0.0050 0.0005 0.0054 0.0041 0.0005 0.0046

N06A X Other antidepressants 0.1215 0.1857 0.3072 0.1274 0.2329 0.3603 N06A X03 Mianserin 0.0018 0.0002 0.0020 0.0013 0.0001 0.0014 N06A X11 Mirtazapine 0.0517 0.0603 0.1119 0.0649 0.0667 0.1315 N06A X12 Bupropion 0.0002 0.0045 0.0048 0.0003 0.0040 0.0043 N06A X14 Tianeptine 0.0001 0.0056 0.0057 0.0001 0.0057 0.0058 N06A X16 Venlafaxine 0.0251 0.0157 0.0408 0.0216 0.0153 0.0369 N06A X21 Duloxetine 0.0252 0.0397 0.0649 0.0222 0.0388 0.0610 N06A X22 Agomelatine 0.0125 0.0294 0.0419 0.0116 0.0298 0.0414 N06A X23 Desvenlafaxine 0.0049 0.0271 0.0320 0.0055 0.0280 0.0335 N06A X26 Vortioxetine - 0.0031 0.0031 - 0.0444 0.0444

N06B Psychostimulants, agents used 0.0648 0.1636 0.2284 0.0466 0.1485 0.1951 for ADHD and nootropics

N06B A Centrally acting 0.0373 0.0132 0.0504 0.0230 0.0122 0.0351 sympathomimetics N06B A04 Methylphenidate 0.0349 0.0125 0.0474 0.0213 0.0115 0.0328 N06B A09 Atomoxetine 0.0024 0.0007 0.0031 0.0016 0.0007 0.0023

N06B C Xanthine derivatives <0.0001 - <0.0001 <0.0001 - <0.0001 N06B C01 Caffeine <0.0001 - <0.0001 <0.0001 - <0.0001

N06B X Other psychostimulants and 0.0275 0.1505 0.1780 0.0236 0.1363 0.1599 nootropics N06B X03 Piracetam 0.0275 0.1505 0.1780 0.0236 0.1363 0.1599

N06D Anti-dementia drugs 0.1072 0.0506 0.1578 0.1370 0.0569 0.1939

N06D A Anticholinesterases 0.0871 0.0256 0.1128 0.1172 0.0317 0.1489 N06D A02 Donepezil 0.0588 0.0188 0.0776 0.0929 0.0243 0.1172 N06D A03 Rivastigmine 0.0283 0.0066 0.0349 0.0243 0.0072 0.0314 N06D A04 Galantamine - 0.0002 0.0002 - 0.0002 0.0002

N06D X Other anti-dementia drugs 0.0201 0.0250 0.0450 0.0198 0.0253 0.0451 N06D X01 Memantine 0.0201 0.0250 0.0450 0.0198 0.0253 0.0451

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Table 13.7 Other nervous system drugs, N07 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

N07A Parasympathomimetics 0.1103 0.0154 0.1257 0.0955 0.0118 0.1073

N07A A Anticholinesterases 0.1103 0.0154 0.1257 0.0955 0.0118 0.1073 N07A A01 Neostigmine 0.0157 0.0070 0.0227 0.0154 0.0049 0.0204 N07A A02 Pyridostigmine 0.0946 0.0084 0.1030 0.0801 0.0068 0.0870

N07B Drugs used in addictive 0.7865 0.3055 1.0920 0.8884 0.3149 1.2032 disorders

N07B A Drugs used in nicotine 0.0191 0.0310 0.0500 0.0075 0.0310 0.0385 dependence N07B A01 Nicotine 0.0036 0.0225 0.0261 0.0003 0.0251 0.0253 N07B A03 Varenicline 0.0155 0.0084 0.0239 0.0072 0.0059 0.0131

N07B B Drugs used in alcohol 0.0021 0.0005 0.0026 0.0028 0.0007 0.0035 dependence N07B B04 Naltrexone 0.0021 0.0005 0.0026 0.0028 0.0007 0.0035

N07B C Drugs used in opioid 0.7654 0.2740 1.0393 0.8781 0.2832 1.1613 dependence N07B C01 Buprenorphine - - - 0.0001 - 0.0001 N07B C02 Methadone 0.7648 0.2740 1.0388 0.8764 0.2807 1.1571 N07B C51 Buprenorphine, combinations 0.0006 - 0.0006 0.0016 0.0025 0.0041

N07C Antivertigo preparations 0.3006 0.7923 1.0929 0.3239 0.7933 1.1172

N07C A Antivertigo preparations 0.3006 0.7923 1.0929 0.3239 0.7933 1.1172 N07C A01 Betahistine 0.2342 0.5569 0.7912 0.2794 0.5784 0.8578 N07C A02 Cinnarizine 0.0482 0.1735 0.2217 0.0300 0.1282 0.1582 N07C A03 Flunarizine 0.0182 0.0619 0.0801 0.0144 0.0867 0.1011

N07X Other nervous system drugs 0.0005 0.0007 0.0012 <0.0001 0.0006 0.0007

N07X X Other nervous system drugs 0.0005 0.0007 0.0012 <0.0001 0.0006 0.0007 N07X X02 Riluzole 0.0003 0.0005 0.0008 <0.0001 0.0004 0.0004 N07X X06 Tetrabenazine <0.0001 - <0.0001 - - - N07X X07 Fampridine 0.0002 0.0002 0.0004 - 0.0002 0.0002 N07X X09 Dimethyl fumarate 0.0001 <0.0001 0.0001 - 0.0001 0.0001

Utilisation of drugs for neurological disorders 13.2 Zariah Abdul Aziz, Norsima Nazifah Sidek, Sapiah Sapuan, Tee Sow Kuan, Tan Ai Leen, Puvanarajah SD

Four major categories of neurological drugs for 2015 and 2016 were analysed, namely the antiepileptic drugs (AEDs), anti-parkinson drugs, anti-migraine medicines and other central nervous system (CNS) drugs.

Overall, these drugs showed a reducing trend in DDD/1,000 inhabitants/day. AEDs were the most frequently prescribed group of neurological drugs for both years at 2.1723 and 2.0697 DDD/1,000 inhabitants/day, respectively. This can be explained by its usage in other conditions such as treatment for migraine, neuropathic pain and selected psychiatric conditions.1 In the second place was anti-parkinson drugs at 0.8925 and 0.8255 DDD/1,000 inhabitants/day, respectively.

Antiepileptic drugs

The three most commonly prescribed AEDs for 2015 and 2016 were valproic acid, phenytoin and carbamazepine (Table 13.3). They remained as the most widely used first-line therapy over the two years,

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as they are easily available. Valproic acid was also used as a mood stabiliser and for migraine prophylaxis,2 phenytoin for myotonia3 and carbamazepine for neuropathic pain as well.

For newer AEDs, levetiracetam and lamotrigine were the preferred choices, as they have a better safety profile for women of child-bearing age.1

Overall, the lowest usage of AEDs was noted for oxcarbazepine, vigabatrin, stiripentol, lacosamide and perampanel.

Anti-parkinson drugs

The main classes of anti-parkinson drugs were levodopa (plus peripheral dopamine decarboxylase inhibitors), enzyme inhibitors (catechol-O-methyltransferase inhibitors and monoamine oxidase B inhibitors) and dopamine agonists (ergot and non-ergot). Trihexyphenidyl remained the most commonly used anticholinergic despite the side effects encountered particularly in older patients and those with cognitive impairment (Table 13.4).4

Among the dopaminergic agents, levodopa plus dopamine decarboxylase inhibitor had the highest utilisation being the gold standard for Parkinson’s disease. In the dopamine agonist group, pramipexole was the preferred choice with an increasing trend of usage seen, compared to higher income countries such as Finland, where the Finnish usage was 30 folds higher than Malaysians.5

Anti-migraine drugs

Migraine treatment comprises of acute (abortive) and preventive therapy. For abortive therapy, ergot was widely used in the private sector, with four to five-fold higher in total usage compared to sumatriptan (Table 13.2).

For preventive therapy, pizotifen usage remained low at 0.0192 and 0.0152 DDD/1,000 inhabitants/day for respective years. The usage appeared low because of the tendency to use other groups of drugs which include tricyclic antidepressants, beta-blockers, calcium-channel blockers, anti-vertigo and AEDs.6

Other nervous system drugs

Other nervous system drugs were categorised as anticholinesterases, antivertigo preparations, and other nervous system drugs (Table 13.7).

Among the anticholinesterases, pyridostigmine was the most widely used for myasthenia gravis. Parenteral neostigmine was mainly used for reversal of neuromuscular blockade, and occasionally as off- label use for diagnosis of myasthenia gravis. The usage remained constant throughout 2015 to 2016.

Among the antivertigo preparations, betahistine remained the drug of choice for vertigo. This was followed by cinnarizine and flunarizine.

Other nervous system drugs include riluzole for motor neuron disease, tetrabenazine for movement disorders, fampridine and dimethyl fumarate for multiple sclerosis.

Interferon Beta-1A and 1B remained the first-line treatment for multiple sclerosis with higher usage in government hospitals (Table 11.8).

Among the immunosuppressants, a higher usage was seen with azathioprine and methotrexate (Table 11.9).

It was also noted that the usage of alteplase was minimal at less than 0.0001 DDD/1,000 inhabitants/day though alteplase had been listed in the MoHMF for hyperacute stroke therapy since 2012 (Table 5.2).

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Utilisation of drugs for psychiatric disorders 13.3 Norhalina Bahar, Chin Loi Fei, Azizul Awaluddin, Noormazita Mislan

The National Health and Morbidity Survey (NHMS) 2015 showed a marked increase in prevalence of psychiatric morbidity, where 29.2% of adults suffered from mental health issues, a three-fold increase from 10.6% in NHMS 1996. Ironically, the total utilisation of psycholeptic agents had decreased from 2015 to 2016. These included antipsychotic group, anxiolytics, antidepressants and parasympathomimetic agents, with respective utilisation had reduced from 2.6696 to 2.6052, 1.1698 to 0.9975, 2.0988 to 1.9627 and 0.1257 to 0.1073 DDD/1,000 inhabitants/day. In the following paragraphs, the value presented also is based on DDD/1,000 inhabitants/day.

Antipsychotics

In 2015 and 2016, the overall use of antipsychotics was more prevalent in public sector (Table 13.5). Predominantly, atypical antipsychotics were the most utilised antipsychotics and the usage of typical antipsychotic was evidently decreased from 2015 to 2016. In comparison for 2015 and 2016, risperidone was the most utilised atypical antipsychotic, followed by olanzapine while fluphenazine was the most utilised typical antipsychotic. The usage of lithium was low as shown by the DDD of 0.0705 in 2015 and 0.0947 in 2016. This might be due to serum lithium monitoring service which was not widely provided in many hospitals. In addition, psychiatrists prefer to use sodium valproate, carbamazepine and lamotrigine as mood stabilizers.

Anxiolytics, hypnotics and sedatives

There was a reduction of 10.7% in the overall use of anxiolytics, hypnotics and sedatives in 2015 as compared to 2016, respectively 1.5594 and 1.3918 (Table 13.5). The private sector had used 1.1917, which is 76.4% of the total utilisation of anxiolytics, hypnotics and sedatives class in 2015 and 74.5% in 2016 (1.0374 DDD/1,000 inhabitants/day) in contrast with public sector.

For 2015, alprazolam was the most commonly prescribed anxiolytics. The great usage impact was from the private sector, 0.4773 compared to total utilisation of 0.5567. In fact, the use of alprazolam was 2.4 folds the total use of diazepam which is 0.2366. Interestingly, in 2016, diazepam was the largest prescribed anxiolytics while there was a substantial reduction in the usage of alprazolam, with utilisation of 0.2903 and 0.2511, respectively. The legal provision and recent enforcement by relevant authorities to curb misuse of these medicines could likely be the reason for this decline.

Antidepressants

Consumption of antidepressants had shown a reduction from 2.0988 in 2015 to 1.9627 in 2016.

Among the different classes, selective serotonin reuptake inhibitors (SSRIs) remained the biggest contributor in terms of proportion, i.e. 74.2% in 2015 and 71.6% in 2016 (Table 13.6). The top three SSRIs were escitalopram, fluvoxamine and sertraline. In total, escitalopram was the most widely used antidepressant both in 2015 and 2016 with respective DDD/1,000 inhabitants/day of 0.5112 and 0.5277. Ecitalopram’s profile as one of the SSRIs with the least drug-drug interaction might have encouraged its use in special population such as the medically ill group of patients, and it was also prescribed by other health care professionals of various specialties in private practice. Overall, non-SSRI antidepressants had showed reduction in usage, except for mirtazapine which had increased from 0.1119 in 2015 to 0.1315 in 2016 and the multimodal serotonin modulator vortioxetine, increased 0.0413 DDD/1,000 inhabitants/day to 0.0444 in 2016.

Utilisation of antidepressants was higher in public sector as compared to private sector. However, the trend of using other antidepressants, for example vortioxetine, mirtazapine and agomelatine was more prominent in private sector than in public sector (0.1857 versus 0.1215 in 2015 and 0.2329 versus 0.1274 in 2016).

Psychostimulants, agents used for ADHD and nootropics

Psychostimulants were most commonly used for treatment of attention deficit hyperactive disorder (ADHD), specifically methylphenidate with utilisation of 0.0474 and 0.0328 for 2015 and 2016, respectively (Table 13.6). Interestingly, the use of psychostimulant agents for ADHD and nootropics was higher in

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private sector, above 70% of total utilisation. Specifically, despite a lower usage of atomoxetine, it showed a slight decrease in trend, from 0.0031 in 2015 to 0.0023 in 2016. Interestingly, piracetam as a nootropic was used more frequently at 0.1780 and 0.1599, respectively for both years.

Anti-dementia drugs

Anti-dementia drugs usage had increased by 22.9%, from 0.1578 in 2015 to 0.1939 in 2016 (Table 13.6). Donepezil remained the most commonly prescribed anti-dementia drugs for 2015 and 2016. In 2015, the use of memantine was higher in private sector with utilisation of 0.0250 while donepezil use was 0.0188. Nevertheless, the utilisation of memantine and donepezil in the private sector was almost equal in 2016.

Drugs used in addictive disorders

As a group, usage of drugs for addictive disorders however had shown an increasing trend from 1.0920 in 2015 to 1.2032 in 2016 (Table 13.7). There was about 10.2% increment of use in which methadone was the most widely prescribed agent. Overall, usage in public sector was higher as compared to private sector which were 72.0% in 2015 and 73.8% in 2016.

The use of methadone in opioid dependence had increased by 11.4% in 2016 in which 75.7% was prescribed by the public sector (0.8764 DDD/1,000 inhabitants/day). Buprenorphine combination was not documented in 2015 for the private sector. Interestingly, utilisation in 2016 showed remarkable usage in private sector as compared to the public sector, which had contributed 61.0% of total use. Buprenorphine use was only documented by the public sector of 0.0001 in 2016 but no utilisation was showed in 2015.

The second most commonly used group of medicines for addictive disorders was for nicotine dependence. Total utilisation of nicotine had decreased 0.0008 to 0.0253 in 2016. Despite the down trend use of nicotine, the prescription was predominant in private sector, 86.2% and 99.2%, respectively in 2015 and 2016. The trend of varenicline use had shown similar pattern of reduction, from 0.0239 in 2015 to 0.0131 in 2016. It was mainly prescribed by the public health practitioners, respectively 64.9% and 55.0% in 2015 and 2016.

Naltrexone remained the treatment of choice being used for alcohol dependence and the data showed an increasing trend of total use by 34.6%, to 0.0035 DDD/1000 inhabitants/day in 2016. It was mainly prescribed in public sector in 2015 and 2016, 80.8% and 80.0%, respectively.

In conclusion, psycholeptics utilisation showed a decreased trend from 2015 to 2016, despite the worrying prevalence of mental health problems. There are several possible explanations to reflect such interesting findings. Mental health concerns have becoming an important integral of well-being. Hence, numerous efforts from various stakeholders were as important as pharmacotherapy, such as practicing psychosocial interventions towards effective mental health literacy and awareness, and providing easy accessibility to mental health services.

REFERENCES

1. Raymond A. A.; Tan, C. T.; Raihanah A. K.; et al. (Eds). Consensus Guidelines on the Management of Epilepsy 2010; Malaysian Society of Neurosciences: Kuala Lumpur, 2010. 2. Rosenberg, G. The Mechanism of Action of Valproate in Neuropsychiatric Disorders: Can We See the Forest for the Trees? Cell. Mol. Life Sci. 2007, 64(16), 2090‐2103. 3. Finkel, M. J. Phenytoin Revisited. Clin. Ther. 1984, 6(5), 577‐591. 4. Lim, S. Y.; Norlinah M. I.; Puvanarajah, S.; et al. 2012 Consensus Guidelines for the Treatment of Parkinson’s Disease; Movement Disorders Council: Kuala Lumpur, 2012. 5. Finnish Statistics on Medicines 2015; Finnish Medicines Agency and Social Insurance Institution: Helsinki, 2016. 6. Becker, W. J.; Findlay, T.; Moga, C.; et al. Guideline for Primary Care Management of Headache in Adults. Can. Fam. Physician 2015, 61, 670-679.

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14 Antiparasitic Products

Statistics on antiparasitic products 14.1

Table 14.1 Statistics by therapeutic groups of antiparasitic products, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

P Antiparasitic products, 0.3663 0.2387 0.6050 0.3105 0.2157 0.5262 insecticides and repellents

P01 Antiprotozoals 0.1940 0.1601 0.3541 0.1607 0.1377 0.2985 P02 Anthelmintics 0.1723 0.0787 0.2510 0.1498 0.0780 0.2278

Table 14.2 Statistics by therapeutic groups of antiparasitic products, in public and private sector (Utilisation in DDD/inhabitant/year) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

P Antiparasitic products, 0.1337 0.0871 0.2208 0.1137 0.0789 0.1926 insecticides and repellents

P01 Antiprotozoals 0.0708 0.0584 0.1292 0.0588 0.0504 0.1092 P02 Anthelmintics 0.0629 0.0287 0.0916 0.0548 0.0285 0.0834

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Table 14.3 Antiprotozoals, P01 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

P01A Agents against 0.0944 0.1358 0.2302 0.0865 0.1172 0.2037 0.0345 0.0496 0.0840 0.0317 0.0429 0.0746 amoebiasis and other protozoal diseases

P01A B Nitroimidazole 0.0944 0.1358 0.2302 0.0865 0.1172 0.2037 0.0345 0.0496 0.0840 0.0317 0.0429 0.0746 derivatives P01A B01 Metronidazole 0.0944 0.1350 0.2294 0.0865 0.1168 0.2034 0.0345 0.0493 0.0837 0.0317 0.0428 0.0744 P01A B02 Tinidazole - 0.0008 0.0008 - 0.0003 0.0003 - 0.0003 0.0003 - 0.0001 0.0001

P01B Antimalarials 0.0995 0.0243 0.1238 0.0741 0.0206 0.0946 0.0363 0.0089 0.0452 0.0271 0.0075 0.0346

P01B A Aminoquinolines 0.0943 0.0217 0.1160 0.0715 0.0183 0.0898 0.0344 0.0079 0.0423 0.0262 0.0067 0.0329 P01B A01 Chloroquine 0.0079 0.0013 0.0091 0.0011 - 0.0011 0.0029 0.0005 0.0033 0.0004 - 0.0004 P01B A02 Hydroxychloroquine 0.0823 0.0201 0.1024 0.0652 0.0183 0.0835 0.0300 0.0073 0.0374 0.0239 0.0067 0.0306

P01B A03 Primaquine 0.0041 0.0004 0.0045 0.0052 <0.0001 0.0052 0.0015 0.0001 0.0016 0.0019 <0.0001 0.0019 107

P01B B Biguanides <0.0001 0.0011 0.0011 - 0.0008 0.0008 <0.0001 0.0004 0.0004 - 0.0003 0.0003 P01B B51 Proguanil, <0.0001 0.0011 0.0011 - 0.0008 0.0008 <0.0001 0.0004 0.0004 - 0.0003 0.0003 combinations

P01B C Methanolquinolines 0.0002 <0.0001 0.0002 <0.0001 <0.0001 <0.0001 0.0001 <0.0001 0.0001 <0.0001 <0.0001 <0.0001 P01B C01 Quinine 0.0002 <0.0001 0.0002 <0.0001 - <0.0001 0.0001 <0.0001 0.0001 <0.0001 - <0.0001 P01B C02 Mefloquine - <0.0001 <0.0001 - <0.0001 <0.0001 - <0.0001 <0.0001 - <0.0001 <0.0001

P01B D Diaminopyrimidines 0.0039 0.0013 0.0052 0.0019 0.0013 0.0033 0.0014 0.0005 0.0019 0.0007 0.0005 0.0012 P01B D01 Pyrimethamine 0.0009 - 0.0009 0.0004 - 0.0004 0.0003 - 0.0003 0.0001 - 0.0001 P01B D51 Pyrimethamine, 0.0030 0.0013 0.0043 0.0016 0.0013 0.0029 0.0011 0.0005 0.0016 0.0006 0.0005 0.0011 combinations

P01B E Artemisinin and 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 derivatives, plain P01B E03 Artesunate 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

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Table 14.3 (continued) ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

P01B F Artemisinin and 0.0011 0.0001 0.0011 0.0005 <0.0001 0.0006 0.0004 <0.0001 0.0004 0.0002 <0.0001 0.0002 derivatives, combinations P01B F01 Artemether and 0.0004 0.0001 0.0004 0.0005 <0.0001 0.0006 0.0001 <0.0001 0.0002 0.0002 <0.0001 0.0002 lumefantrine P01B F02 Artesunate and 0.0007 - 0.0007 - - - 0.0003 - 0.0003 - - - mefloquine

P01C Agents against 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.0001 leishmaniasis and trypanosomiasis

P01C X Other agents against 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.0001 leishmaniasis and

trypanosomiasis 1

0 P01C X01 Pentamidine 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.0001 8

isethionate

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Table 14.4 Antihelmintics, P02 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

P02C Antinematodal agents 0.1723 0.0787 0.2510 0.1498 0.0780 0.2278 0.0629 0.0287 0.0916 0.0548 0.0285 0.0834

P02C A Benzimidazole 0.1708 0.0783 0.2491 0.1498 0.0771 0.2269 0.0623 0.0286 0.0909 0.0548 0.0282 0.0830 derivatives P02C A01 Mebendazole - 0.0118 0.0118 - 0.0079 0.0079 - 0.0043 0.0043 - 0.0029 0.0029 P02C A03 Albendazole 0.1708 0.0665 0.2373 0.1498 0.0692 0.2190 0.0623 0.0243 0.0866 0.0548 0.0253 0.0802

P02C C Tetrahydropyrimidine - 0.0003 0.0003 - 0.0009 0.0009 - 0.0001 0.0001 - 0.0003 0.0003 derivatives P02C C01 Pyrantel - 0.0003 0.0003 - 0.0009 0.0009 - 0.0001 0.0001 - 0.0003 0.0003

P02C E Imidazothiazole 0.0015 - 0.0015 - - - 0.0006 - 0.0006 - - - derivatives P02C E01 Levamisole 0.0015 - 0.0015 - - - 0.0006 - 0.0006 - - -

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Utilisation of antimalarials 14.2 Leong Chee Loon, Steven Lim Chee Loon, Rahela Ambaras Khan, Preethi Raghavan, Hannah Md Mahir, Mak Woh Yon

Among antimalarial agents, arthemeter/lumefantrine combination was the most common agent with a 1.5-fold increment (Table 14.3). This shows a paradigm shift in favour of fixed-dose combinations (FDC) as compared to the individual conventional agents.

110

15 Respiratory System

Statistics on medicines for respiratory system 15.1

Table 15.1 Statistics by therapeutic groups for respiratory system, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

R Respiratory system 16.8111 33.4937 50.3047 14.9787 33.2894 48.2681

R01 Nasal preparations 0.9372 3.9439 4.8811 0.7375 3.9016 4.6391 R03 Drugs for obstructive airway 9.2977 5.5902 14.8878 8.5853 5.3016 13.8869 diseases R05 Cough and cold preparations 0.9183 6.8790 7.7973 0.8765 6.7969 7.6734 R06 Antihistamines for systemic use 5.6576 17.0806 22.7382 4.7791 17.2892 22.0683 R07 Other respiratory system 0.0003 <0.0001 0.0004 0.0003 <0.0001 0.0004 products

Table 15.2 Statistics by therapeutic groups for respiratory system, in public and private sector (Utilisation in DDD/inhabitant/year) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

R Respiratory system 2.7424 10.1848 12.9271 2.3399 10.2436 12.5835

R01 Nasal preparations 0.3421 1.4395 1.7816 0.2699 1.4280 1.6979 R05 Cough and cold preparations 0.3352 2.5108 2.8460 0.3208 2.4877 2.8085 R06 Antihistamines for systemic use 2.0650 6.2344 8.2994 1.7491 6.3279 8.0770 R07 Other respiratory system 0.0001 <0.0001 0.0001 0.0001 <0.0001 0.0001 products

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Table 15.3 Nasal preparations, R01 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

R01A Decongestants and 0.8268 2.4511 3.2779 0.6552 2.4949 3.1501 0.3018 0.8946 1.1964 0.2398 0.9131 1.1529 other nasal preparations for topical use

R01A A Sympathomimetics, 0.0254 0.8678 0.8932 0.0169 0.9426 0.9595 0.0093 0.3167 0.3260 0.0062 0.3450 0.3512 plain R01A A05 Oxymetazoline 0.0254 0.8382 0.8636 0.0169 0.9208 0.9377 0.0093 0.3059 0.3152 0.0062 0.3370 0.3432 R01A A07 Xylometazoline - 0.0296 0.0296 - 0.0218 0.0218 - 0.0108 0.0108 - 0.0080 0.0080

R01A C Antiallergic agents, - 0.0002 0.0002 - - - - 0.0001 0.0001 - - - excluding corticosteroids R01A C01 Cromoglicic acid - 0.0002 0.0002 - - - - 0.0001 0.0001 - - -

112 R01A D Corticosteroids 0.8014 1.5832 2.3845 0.6382 1.5523 2.1905 0.2925 0.5779 0.8704 0.2336 0.5681 0.8017

R01A D01 Beclometasone 0.0725 0.0284 0.1009 0.0348 0.0279 0.0627 0.0265 0.0104 0.0368 0.0127 0.0102 0.0229 R01A D05 Budesonide 0.2943 0.4791 0.7734 0.1959 0.4183 0.6142 0.1074 0.1749 0.2823 0.0717 0.1531 0.2248 R01A D08 Fluticasone 0.0171 0.2696 0.2867 0.0071 0.2499 0.2570 0.0063 0.0984 0.1046 0.0026 0.0915 0.0941 R01A D09 Mometasone 0.2961 0.3520 0.6481 0.3137 0.3916 0.7053 0.1081 0.1285 0.2366 0.1148 0.1433 0.2581 R01A D11 Triamcinolone - 0.0943 0.0943 - 0.1000 0.1000 - 0.0344 0.0344 - 0.0366 0.0366 R01A D12 Fluticasone furoate 0.1194 0.2894 0.4088 0.0860 0.3123 0.3983 0.0436 0.1056 0.1492 0.0315 0.1143 0.1458 R01A D13 Ciclesonide 0.0019 0.0704 0.0723 0.0007 0.0524 0.0531 0.0007 0.0257 0.0264 0.0003 0.0192 0.0194

R01B Nasal decongestants 0.1104 1.4928 1.6031 0.0823 1.4067 1.4890 0.0403 0.5449 0.5851 0.0301 0.5149 0.5450 for systemic use

R01B A Sympathomimetics 0.1104 1.4928 1.6031 0.0823 1.4067 1.4890 0.0403 0.5449 0.5851 0.0301 0.5149 0.5450 R01B A52 Pseudoephedrine, 0.1104 1.3947 1.5051 0.0823 1.3191 1.4014 0.0403 0.5091 0.5493 0.0301 0.4828 0.5129 combinations R01B A53 Phenylephrine, - 0.0981 0.0981 - 0.0876 0.0876 - 0.0358 0.0358 - 0.0321 0.0321 combinations

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Table 15.4 Adrenergics for obstructive airway diseases, inhalants, R03A (Utilisation in DDD/1,000 inhabitants /day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

R03A Adrenergics, inhalants 4.7925 3.6542 8.4468 4.4439 3.4592 7.9031

R03A C Selective beta-2- 3.4770 2.7114 6.1884 3.0800 2.4613 5.5413 adrenoreceptor agonists R03A C02 Salbutamol 3.4186 2.6627 6.0813 3.0570 2.4187 5.4757 R03A C03 Terbutaline 0.0397 0.0107 0.0505 0.0127 0.0085 0.0212 R03A C04 Fenoterol - 0.0296 0.0296 0.0009 0.0296 0.0305 R03A C13 Formoterol 0.0055 0.0007 0.0063 0.0007 0.0007 0.0014 R03A C18 Indacaterol 0.0131 0.0078 0.0208 0.0087 0.0037 0.0124 R03A C19 Olodaterol - - - - 0.0001 0.0001

R03A K Adrenergics in combination 0.6165 0.7171 1.3336 0.7851 0.7525 1.5377 with corticosteroids or other drugs, excluding anticholinergics R03A K06 Salmeterol and fluticasone 0.4023 0.3995 0.8018 0.5337 0.4007 0.9344 R03A K07 Formoterol and budesonide 0.2054 0.2720 0.4774 0.2500 0.2602 0.5101 R03A K08 Formoterol and 0.0087 0.0155 0.0242 0.0015 0.0184 0.0199 beclometasone R03A K09 Formoterol and mometasone 0.0001 0.0006 0.0007 - - - R03A K10 Vilanterol and fluticasone - 0.0031 0.0031 - 0.0319 0.0319 furoate R03A K11 Formoterol and fluticasone - 0.0145 0.0145 - 0.0329 0.0329 R03A K13 Salbutamol and - 0.0119 0.0119 - 0.0084 0.0084 beclometasone

R03A L Adrenergics in combinations 0.6991 0.2257 0.9248 0.5788 0.2453 0.8241 with anticholinergics including triple combinations with corticosteroids R03A L01 Fenoterol and ipratropium 0.4767 0.1500 0.6266 0.3512 0.1562 0.5074 bromide R03A L02 Salbutamol and ipratropium 0.2224 0.0703 0.2927 0.2266 0.0708 0.2973 bromide R03A L03 Vilanterol and umeclidinium - - - - 0.0022 0.0022 bromide R03A L04 Indacaterol and - 0.0054 0.0054 0.0011 0.0161 0.0172 glycopyrronium bromide

Table 15.5 Other drugs for obstructive airway diseases, inhalants, R03B (Utilisation in DDD/1,000 inhabitants /day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

R03B Other drugs for obstructive 3.6671 0.2988 3.9659 3.3844 0.2778 3.6623 airway diseases, inhalants

R03B A Glucocorticoids 3.0765 0.2142 3.2907 3.0329 0.1873 3.2201 R03B A01 Beclometasone 0.2644 0.0126 0.2770 0.2397 0.0052 0.2450 R03B A02 Budesonide 2.5870 0.0774 2.6644 2.4663 0.0658 2.5321 R03B A05 Fluticasone 0.2081 0.0958 0.3038 0.3210 0.0909 0.4119 R03B A08 Ciclesonide 0.0170 0.0284 0.0454 0.0058 0.0253 0.0311

R03B B Anticholinergics 0.5906 0.0846 0.6752 0.3516 0.0905 0.4421 R03B B01 Ipratropium bromide 0.2207 0.0385 0.2593 0.1554 0.0386 0.1939 R03B B04 Tiotropium bromide 0.3692 0.0423 0.4115 0.1962 0.0496 0.2459 R03B B06 Glycopyrronium bromide 0.0007 0.0038 0.0045 - 0.0023 0.0023

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Table 15.6 Systemic adrenergics for obstructive airway diseases, R03C (Utilisation in DDD/1,000 inhabitants /day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

R03C Adrenergics for systemic use 0.2058 0.7561 0.9619 0.0935 0.6437 0.7372

R03C C Selective beta-2- 0.2058 0.7561 0.9619 0.0935 0.6437 0.7372 adrenoreceptor agonists R03C C02 Salbutamol 0.1869 0.6014 0.7883 0.0873 0.5118 0.5990 R03C C03 Terbutaline 0.0189 0.1038 0.1227 0.0062 0.0933 0.0995 R03C C04 Fenoterol - 0.0155 0.0155 - 0.0022 0.0022 R03C C08 Procaterol - 0.0041 0.0041 - 0.0035 0.0035 R03C C13 Clenbuterol - 0.0313 0.0313 - 0.0330 0.0330

Table 15.7 Other systemic drugs for obstructive airway diseases, R03D (Utilisation in DDD/1,000 inhabitants /day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

R03D Other systemic drugs for 0.6322 0.8810 1.5133 0.6635 0.9209 1.5844 obstructive airway diseases

R03D A Xanthines 0.5146 0.3846 0.8993 0.4887 0.3587 0.8474 R03D A04 Theophylline 0.5128 0.3797 0.8924 0.4872 0.3541 0.8413 R03D A05 Aminophylline 0.0018 0.0002 0.0020 0.0015 0.0001 0.0016 R03D A54 Theophylline, combinations - 0.0048 0.0048 - 0.0045 0.0045 excluding psycholeptics

R03D C Leukotriene receptor 0.1162 0.4930 0.6092 0.1738 0.5590 0.7327 antagonists R03D C03 Montelukast 0.1162 0.4930 0.6092 0.1738 0.5590 0.7327

R03D X Other systemic drugs for 0.0014 0.0034 0.0048 0.0011 0.0032 0.0043 obstructive airway diseases R03D X05 Omalizumab 0.0004 0.0003 0.0007 0.0004 0.0003 0.0008 R03D X07 Roflumilast 0.0009 0.0031 0.0041 0.0006 0.0028 0.0035

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Table 15.8 Cough and cold preparations, R05 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

R05C Expectorants, 0.9181 5.0974 6.0156 0.8754 5.1340 6.0095 0.3351 1.8606 2.1957 0.3204 1.8791 2.1995 excluding combinations with cough suppressants

R05C A Expectorants - 3.3638 3.3638 0.0056 3.4466 3.4522 - 1.2278 1.2278 0.0021 1.2615 1.2635 R05C A03 Guaifenesin - 0.0927 0.0927 - 0.0770 0.0770 - 0.0338 0.0338 - 0.0282 0.0282 R05C A10 Expectorants, - 3.2711 3.2711 0.0056 3.3696 3.3753 - 1.1940 1.1940 0.0021 1.2333 1.2353 combinations

R05C B Mucolytics 0.9181 1.7336 2.6518 0.8698 1.6874 2.5572 0.3351 0.6328 0.9679 0.3183 0.6176 0.9360 R05C B01 Acetylcysteine 0.0058 0.3109 0.3167 0.0056 0.3059 0.3116 0.0021 0.1135 0.1156 0.0021 0.1120 0.1140 R05C B02 Bromhexine 0.9120 0.6318 1.5438 0.8638 0.5727 1.4365 0.3329 0.2306 0.5635 0.3161 0.2096 0.5257 R05C B03 Carbocisteine - 0.2127 0.2127 - 0.2073 0.2073 - 0.0776 0.0776 - 0.0759 0.0759 R05C B06 Ambroxol 0.0003 0.2988 0.2991 0.0004 0.2937 0.2940 0.0001 0.1091 0.1092 0.0001 0.1075 0.1076 115 R05C B10 Mucolytics, - 0.2795 0.2795 - 0.3078 0.3078 - 0.1020 0.1020 - 0.1127 0.1127

combinations

R05D Cough suppressants, 0.0002 1.5081 1.5083 0.0010 1.4607 1.4617 0.0001 0.5505 0.5505 0.0004 0.5346 0.5350 excluding combinations with expectorants

R05D A Opium alkaloids and 0.0002 1.2903 1.2905 0.0010 1.2744 1.2754 0.0001 0.4710 0.4710 0.0004 0.4664 0.4668 derivatives R05D A08 Pholcodine 0.0002 0.1224 0.1225 0.0002 0.1185 0.1186 0.0001 0.0447 0.0447 0.0001 0.0434 0.0434 R05D A09 Dextromethorphan - 0.3365 0.3365 0.0009 0.3215 0.3224 - 0.1228 0.1228 0.0003 0.1177 0.1180 R05D A20 Opium alkaloids and - 0.8314 0.8314 - 0.8344 0.8344 - 0.3035 0.3035 - 0.3054 0.3054 derivatives, combinations

R05D B Other cough - 0.2179 0.2179 - 0.1863 0.1863 - 0.0795 0.0795 - 0.0682 0.0682 suppressants R05D B21 Cloperastine - 0.2179 0.2179 - 0.1863 0.1863 - 0.0795 0.0795 - 0.0682 0.0682

115

Table 15.8 (continued) ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

R05F Cough suppressants - 0.2734 0.2734 - 0.2021 0.2021 - 0.0998 0.0998 - 0.0740 0.0740 and expectorants, combinations

R05F A Opium derivatives and - 0.0450 0.0450 - 0.0517 0.0517 - 0.0164 0.0164 - 0.0189 0.0189 expectorants R05F A01 Opium derivatives and - 0.0447 0.0447 - 0.0517 0.0517 - 0.0163 0.0163 - 0.0189 0.0189 mucolytics R05F A02 Opium derivatives and - 0.0003 0.0003 - - - - 0.0001 0.0001 - - - expectorants

R05F B Other cough - 0.2284 0.2284 - 0.1504 0.1504 - 0.0834 0.0834 - 0.0551 0.0551 suppressants and expectorants R05F B01 Cough suppressants - 0.1497 0.1497 - 0.1043 0.1043 - 0.0546 0.0546 - 0.0382 0.0382 116 and mucolytics

R05F B02 Cough suppressants - 0.0788 0.0788 - 0.0462 0.0462 - 0.0287 0.0287 - 0.0169 0.0169 and expectorants

116

Table 15.9 Antihistamines for systemic use, R06 ATC code Drug/Chemical Utilisation in DDD/1,000 inhabitants/day Utilisation in DDD/inhabitant/year substance 2015 2016 2015 2016 Public Private Total Public Private Total Public Private Total Public Private Total

R06A Antihistamines for 5.6576 17.0806 22.7382 4.7791 17.2892 22.0683 2.0650 6.2344 8.2994 1.7491 6.3279 8.0770 systemic use

R06A A Aminoalkyl ethers 0.7460 0.2672 1.0132 0.6228 0.2418 0.8646 0.2723 0.0975 0.3698 0.2279 0.0885 0.3164 R06A A02 Diphenhydramine 0.7460 0.2544 1.0004 0.6228 0.2418 0.8646 0.2723 0.0929 0.3652 0.2279 0.0885 0.3164 R06A A04 Clemastine - 0.0127 0.0127 - - - - 0.0046 0.0046 - - -

R06A B Substituted 2.1031 3.6554 5.7585 1.8150 3.0965 4.9115 0.7676 1.3342 2.1018 0.6643 1.1333 1.7976 alkylamines R06A B02 Dexchlorpheniramine 0.0046 0.9039 0.9085 0.0007 0.7295 0.7302 0.0017 0.3299 0.3316 0.0003 0.2670 0.2673 R06A B04 Chlorphenamine 2.0985 2.7515 4.8500 1.8143 2.3670 4.1812 0.7660 1.0043 1.7703 0.6640 0.8663 1.5303

R06A D Phenothiazine 0.0849 1.2830 1.3679 0.0700 1.1067 1.1767 0.0310 0.4683 0.4993 0.0256 0.4051 0.4307 derivatives R06A D02 Promethazine 0.0849 1.2830 1.3679 0.0700 1.1060 1.1759 0.0310 0.4683 0.4993 0.0256 0.4048 0.4304 117 R06A D07 Mequitazine - - - - 0.0008 0.0008 - - - - 0.0003 0.0003

R06A E Piperazine derivatives 0.5624 8.3266 8.8891 0.3138 8.8309 9.1448 0.2053 3.0392 3.2445 0.1149 3.2321 3.3470 R06A E01 Buclizine - 0.0080 0.0080 - 0.0086 0.0086 - 0.0029 0.0029 - 0.0031 0.0031 R06A E07 Cetirizine 0.4506 7.3811 7.8318 0.2769 7.7533 8.0302 0.1645 2.6941 2.8586 0.1013 2.8377 2.9390 R06A E09 Levocetirizine 0.0964 0.9052 1.0016 0.0231 1.0345 1.0576 0.0352 0.3304 0.3656 0.0084 0.3786 0.3871 R06A E55 Meclozine, 0.0154 0.0323 0.0477 0.0139 0.0346 0.0485 0.0056 0.0118 0.0174 0.0051 0.0127 0.0177 combinations

R06A X Other antihistamines 2.1612 3.5484 5.7096 1.9575 4.0133 5.9707 0.7888 1.2952 2.0840 0.7164 1.4689 2.1853 for systemic use R06A X13 Loratadine 2.1142 2.4021 4.5164 1.9044 2.7172 4.6216 0.7717 0.8768 1.6485 0.6970 0.9945 1.6915 R06A X17 Ketotifen - 0.1494 0.1494 - 0.1102 0.1102 - 0.0545 0.0545 - 0.0403 0.0403 R06A X26 Fexofenadine 0.0003 0.4052 0.4056 - 0.4531 0.4531 0.0001 0.1479 0.1480 - 0.1658 0.1658 R06A X27 Desloratadine 0.0466 0.4841 0.5307 0.0531 0.4975 0.5506 0.0170 0.1767 0.1937 0.0194 0.1821 0.2015 R06A X29 Bilastine - 0.1076 0.1076 - 0.2352 0.2352 - 0.0393 0.0393 - 0.0861 0.0861

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Table 15.10 Other respiratory system products, R07 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

R07A Other respiratory system 0.0003 <0.0001 0.0004 0.0003 <0.0001 0.0004 products

R07A A Lung surfactants 0.0003 <0.0001 0.0004 0.0003 <0.0001 0.0004 R07A A02 Natural phospholipids - <0.0001 <0.0001 - <0.0001 <0.0001 R07A A30 Lung surfactants, 0.0003 <0.0001 0.0004 0.0003 <0.0001 0.0003 combinations

Utilisation of antihistamines and nasal decongestants 15.2 Siti Sabzah Mohd Hasim, Abd Razak Ahmad, Zulkiflee Salahuddin, Iskandar Hailani, Amran Mohamad, Jothi Shanmuganathan, Halimuddin Sawali, Leow Wooi Leong

Nasal preparations and antihistamines are medicines commonly used for allergy and nasal symptoms in otorhinolaryngology clinics in Malaysia. Allergic disorders such as allergic rhinitis is a global health problem, affecting 10 to 40% of population.1 Chong and Chew reported a prevalence of 4.5% among adults and 24 to 25.6% among children in Singapore.2 Locally, a 2016 paper reported a prevalence of 18.8% among 462 students from junior high schools in Johor Bahru.3,4

The overall usage of decongestants and other nasal preparations for topical use (R01A) has shown a decreasing trend as opposed to the expected increased in the prevalence of the disease. However, further analysis of the medicines under R01A demonstrates an increase use of plain sympathomimetics preparations (R01A A) from 2011 to 20145 and to 2016. This increase is contributed largely by the private sector.

Mometasone, budesonide and fluticasone furoate are still the most commonly used intranasal steroid preparations since the last report.

Use of antihistamines for systemic use (R06A) has marginally decreased from 2015 to 2016 as shown in Table 15.9. Non-sedative antihistamines, namely piperazine derivatives (R06A E) and other antihistamines for systemic use (R06A X) has shown an increase in utilisation over the sedative antihistamines, which are aminoalkyl ethers (R06A A), substituted alkylamines (R06A B) and phenothiazine derivatives (R06A D). As a whole, use of systemic antihistamines in Malaysia is 22.0683 DDD/1,000 inhabitants/day in 2016, lower in comparison to Finland (52.19 DDD/1,000 inhabitants/day).6

Utilisation of drugs for obstructive airway diseases 15.3 Nabilah Salman Parasi @ Sulaiman, Mona Zaria Nasaruddin, Liew Mei Yao

This report reviews the drug utilisation analysis for obstructive airway diseases based on data obtained between 2015 and 2016. However, the data does not differentiate between drugs used in asthma and chronic obstructive pulmonary disease (COPD). COPD is currently the fourth leading cause of global mortality7 and its prevalence is predicted to rise. The overall estimated COPD prevalence was 6.2%, with 19.1% of subjects having severe COPD.8 Meanwhile, the prevalence of asthma is also increasing in many countries especially among children.9

From 2014 to 2016, the usage of drugs for obstructive airway diseases has decreased from 16.1881 DDD/1,000 inhabitants/day in 2014 to 14.8878 and 13.8869 DDD/1,000 inhabitants/day in 2015 and 2016, respectively. Comparing the use of various drugs for obstructive airway diseases between 2015 and 2016, the total use of inhaled short-acting ß2 adrenoreceptor agonists (SABA) in 2016 has reduced considerably from 6.1614 to 5.5274 DDD/1,000 population/day. This decrease was more significantly seen in public sector (from 3.4583 to 3.0706 DDD/1,000 inhabitants/day) compared to that of private sector (2.7030 to

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2.4568 DDD/1,000 inhabitants/day). Besides, the total use of SABAs and anticholinergic combination in 2016 has also decreased slightly from 0.9193 to 0.8047 DDD/1,000 inhabitants/day, both in public and private sectors.

In addition, compared to 2015, the use of long-acting ß2 adrenoreceptor agonists (LABA) in 2016 has also showed decrease of these drugs (from 0.0271 to 0.0139 DDD/1,000 inhabitants/day). This reduction is due to the availability of combination LABA bronchodilator and long-acting anticholinergic agent for COPD. Besides, tiotropium and glycopyrronium bromide, the long acting anticholinergic, which is indicated for COPD, has also shown a decrease usage in 2016 (0.4160 to 0.2482 DDD/1,000 inhabitants/day).

There was an increasing use of inhaled single-agent glucocorticoids since 2011 (2.7855 DDD/1,000 inhabitants/day) until 2015 (3.2907 DDD/1,000 inhabitants/day). However, in 2016, the use of inhaled glucocorticoids has reduced to 3.2201 DDD/1,000 inhabitants/day. This reduction was particularly more marked in the private sector. One of the reasons could be the use of inhaled glucocorticoids with LABA bronchodilators (ICS/LABA) combination that had increased substantially from 1.3217 to 1.5292 DDD/1,000 inhabitants/day. Underuse of glucocorticoids in the treatment of asthma may lead to more patients with uncontrolled asthma and an increase use of rescue ß2 adrenoreceptor agonists.

The adrenergics in combination with anticholinergics bronchodilator therapy was introduce in private and public sectors for COPD patients. This is following treatment recommendation to achieve optimal bronchodilation. Studies have demonstrated that it reduces symptoms and risk of exacerbations with comparable safety profile. There was an increase use of the medicines in this population group. The use of oral theophylline was unchanged however noted a decline trend from 0.8924 to 0.8413 DDD/1,000 inhabitants/day. Meanwhile, oral montelukast usage increased from 0.6092 to 0.7327 DDD/1,000 inhabitants/day. This could be as an add-on management of poorly controlled asthma or with concomitant allergic rhinitis. The utilisation of omalizumab remained low from 0.0007 to 0.0008 DDD/1,000 inhabitants/day.

Analysis from OECD countries showed that Malaysia has the lowest utilisation of drugs for obstructive airway diseases with 14.9 DDD/1,000 inhabitants/day in year 2015 and 14.5 DDD/1,000 inhabitants/day in year 2016. The average drug utilisation for obstructive airway diseases among OECD countries was 95.9 DDD/1,000 inhabitants/day in year 2015 and 97.3 DDD/1,000 inhabitants/day in year 2016. Comparison with other Asia Pacific countries such as Korea and Australia, Malaysia also showed to has the lowest utilisation of drugs for obstructive airway diseases.10

REFERENCES

1. Broźek, J. L.; Bousquet, J.; Agache, I.; et al. Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines 2016 revision. J. Allergy Clin. Immunol. 2007, 140(4), 950-958. 2. Chong, S. N.; Chew, F. T. Epidemiology of Allergic Rhinitis and Associated Risk Factors in Asia. World Allergy Organization Journal 2018, 11, 17. 3. Norbäck, D.; Hashim J. H,; Markowicz P.; et al. Endotoxin, Ergosterol, Muramic Acid and Fungal DNA in Dust from Schools in Johor Bahru, Malaysia: Associations with Rhinitis and Sick Building Syndrome (SBS) in Junior High School Students. Sci. Total Environ. 2016, 545–546, 95–103. 4. Norbäck, D.; Hashim J. H.; Cai G. H.; et al. Rhinitis, Ocular, Throat and Dermal Symptoms, Headache and Tiredness Among Students in Schools from Johor Bahru, Malaysia: Associations with Fungal DNA and Mycotoxins in Classroom Dust. PLoS One 2016, 11, 1–15. 5. Malaysian Statistics on Medicines 2011-2014; Pharmaceutical Services Division, Ministry of Health Malaysia: Kuala Lumpur, 2017. 6. Finnish Statistics on Medicines 2016; Finnish Medicines Agency and Social Insurance Institution: Helsinki, 2017. 7. The Global Burden of Disease 2004 Update; World Health Organization: Geneva, 2008. 8. Lim, S.; Lam, C. D.; Muttalif, A. R.; et al. Impact of Chronic Obstructive Pulmonary Disease (COPD) In the Asia-Pacific Region: The Epic Asia Population-Based Survey. Asia Pacific Family Medicine 2015, 14, 4. 9. Global Initiative for Asthma: Global strategy for asthma management and prevention 2019. 10. Pharmaceutical Market, Organisation for Economic Co-operation and Development, OECD Stat. https://stats.oecd.org (accessed December 3, 2019).

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16 Sensory Organs

Statistics on medicines for sensory organs 16.1

Table 16.1 Statistics by therapeutic groups for sensory organs, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group 2015 2016 Public Private Total Public Private Total

S Sensory organs 3.4285 3.6536 7.0821 3.7350 3.7840 7.5190

S01 Ophthalmologicals 3.2125 2.6949 5.9074 3.5475 2.9027 6.4502 S02 Otologicals 0.1595 0.0575 0.2170 0.1386 0.0653 0.2039 S03 Ophthalmological and 0.0565 0.9012 0.9578 0.0489 0.8160 0.8649 otological preparations

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Table 16.2 Antiinfectives for ophthalmological system, S01A (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01A Antiinfectives 0.6739 0.6823 1.3562 0.5854 0.7071 1.2925

S01A A Antibiotics 0.6398 0.6087 1.2485 0.5576 0.6294 1.1871 S01A A01 Chloramphenicol 0.6003 0.4902 1.0905 0.5361 0.5175 1.0537 S01A A02 Chlortetracycline 0.0002 0.0004 0.0006 - 0.0001 0.0001 S01A A10 Natamycin 0.0002 0.0001 0.0003 <0.0001 0.0001 0.0002 S01A A11 Gentamicin 0.0151 0.0236 0.0386 0.0048 0.0226 0.0275 S01A A12 Tobramycin - 0.0099 0.0099 - 0.0088 0.0088 S01A A13 Fusidic acid 0.0178 0.0298 0.0477 0.0122 0.0270 0.0392 S01A A17 Erythromycin - 0.0016 0.0016 - 0.0017 0.0017 S01A A30 Combinations of different 0.0062 0.0532 0.0593 0.0045 0.0515 0.0560 antibiotics

S01A D Antivirals 0.0005 - 0.0005 0.0010 0.0007 0.0017 S01A D03 Aciclovir 0.0005 - 0.0005 0.0010 0.0007 0.0017

S01A E Fluoroquinolones 0.0336 0.0736 0.1072 0.0267 0.0770 0.1037 S01A E01 Ofloxacin - - - - 0.0013 0.0013 S01A E03 Ciprofloxacin 0.0222 0.0116 0.0338 0.0142 0.0098 0.0239 S01A E05 Levofloxacin 0.0001 0.0075 0.0076 <0.0001 0.0122 0.0122 S01A E06 Gatifloxacin - 0.0098 0.0098 - 0.0069 0.0069 S01A E07 Moxifloxacin 0.0113 0.0435 0.0548 0.0125 0.0459 0.0584 S01A E08 Besifloxacin - 0.0011 0.0011 - 0.0009 0.0009

Table 16.3 Antiinflammatory agents for ophthalmological system, S01B (Utilisation in DDD/1,000 inhabitants /day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01B Antiinflammatory agents 0.0602 0.1475 0.2077 0.0594 0.1362 0.1957

S01B A Corticosteroids, plain 0.0534 0.1042 0.1576 0.0503 0.0893 0.1396 S01B A01 Dexamethasone 0.0397 0.0280 0.0677 0.0414 0.0278 0.0691 S01B A04 Prednisolone 0.0047 0.0443 0.0490 0.0032 0.0327 0.0358 S01B A07 Fluorometholone 0.0088 0.0253 0.0341 0.0057 0.0243 0.0299 S01B A14 Loteprednol 0.0002 0.0066 0.0068 0.0001 0.0046 0.0047

S01B C Antiinflammatory agents, non- 0.0068 0.0433 0.0502 0.0091 0.0470 0.0561 steroids S01B C05 Ketorolac 0.0060 0.0123 0.0183 0.0086 0.0113 0.0199 S01B C10 Nepafenac 0.0008 0.0310 0.0318 0.0005 0.0357 0.0362

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Table 16.4 Antiinflammatory agents and antiinfectives in combination for ophthalmological system, S01C (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01C Antiinflammatory agents and 0.0412 0.1264 0.1676 0.0423 0.1281 0.1704 antiinfectives in combination

S01C A Corticosteroids and 0.0412 0.1264 0.1676 0.0423 0.1281 0.1704 antiinfectives in combination S01C A01 Dexamethasone and 0.0412 0.1264 0.1676 0.0381 0.1281 0.1662 antiinfectives S01C A05 Betamethasone and - <0.0001 <0.0001 0.0042 - 0.0042 antiinfectives

Table 16.5 Antiglaucoma preparations and miotics, S01E (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01E Antiglaucoma preparations 1.9741 0.8163 2.7904 2.1352 0.7914 2.9266 and miotics

S01E A Sympathomimetics in 0.2060 0.0717 0.2778 0.2238 0.0599 0.2837 glaucoma therapy S01E A05 Brimonidine 0.2060 0.0717 0.2778 0.2238 0.0599 0.2837

S01E B Parasympathomimetics 0.0234 0.0214 0.0448 0.0234 0.0196 0.0430 S01E B01 Pilocarpine 0.0167 0.0214 0.0381 0.0187 0.0196 0.0384 S01E B02 Carbachol 0.0067 - 0.0067 0.0046 - 0.0046

S01E C Carbonic anhydrase inhibitors 0.1894 0.0792 0.2686 0.2437 0.0890 0.3327 S01E C01 Acetazolamide 0.0100 0.0061 0.0162 0.0093 0.0065 0.0158 S01E C03 Dorzolamide 0.1465 0.0123 0.1588 0.1963 0.0164 0.2127 S01E C04 Brinzolamide 0.0328 0.0608 0.0936 0.0381 0.0661 0.1041

S01E D Beta blocking agents 0.9622 0.4532 1.4154 0.8933 0.4385 1.3318 S01E D01 Timolol 0.8571 0.1839 1.0410 0.8014 0.1719 0.9733 S01E D02 Betaxolol 0.0679 0.0284 0.0963 0.0530 0.0250 0.0780 S01E D51 Timolol, combinations 0.0371 0.2410 0.2781 0.0389 0.2416 0.2805

S01E E Prostaglandin analogues 0.5931 0.1908 0.7839 0.7511 0.1844 0.9354 S01E E01 Latanoprost 0.5409 0.0884 0.6292 0.7221 0.0783 0.8003 S01E E03 Bimatoprost 0.0493 0.0333 0.0826 0.0241 0.0249 0.0490 S01E E04 Travoprost 0.0030 0.0682 0.0712 0.0049 0.0593 0.0642 S01E E05 Tafluprost - 0.0010 0.0010 - 0.0219 0.0219

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Table 16.6 Mydriatics and cycloplegics, S01F (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01F Mydriatics and cycloplegics 0.0238 0.0109 0.0347 0.0176 0.0105 0.0281

S01F A Anticholinergics 0.0213 0.0094 0.0308 0.0158 0.0091 0.0249 S01F A01 Atropine 0.0076 0.0015 0.0091 0.0056 0.0017 0.0073 S01F A04 Cyclopentolate 0.0029 0.0031 0.0060 0.0025 0.0026 0.0050 S01F A05 Homatropine 0.0038 0.0011 0.0049 0.0020 0.0011 0.0032 S01F A06 Tropicamide 0.0046 0.0031 0.0077 0.0046 0.0031 0.0077 S01F A54 Cyclopentolate, combinations 0.0024 0.0006 0.0030 0.0011 0.0005 0.0016

S01F B Sympathomimetics excluding 0.0025 0.0015 0.0039 0.0018 0.0014 0.0032 antiglaucoma preparations S01F B01 Phenylephrine 0.0025 0.0015 0.0039 0.0018 0.0014 0.0032

Table 16.7 Decongestants and antiallergics for ophthalmological system, S01G (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01G Decongestants and 0.0247 0.4897 0.5144 0.0138 0.5383 0.5520 antiallergics

S01G A Sympathomimetics used as 0.0008 0.3991 0.3999 0.0007 0.4494 0.4500 decongestants S01G A01 Naphazoline - 0.0079 0.0079 - 0.0452 0.0452 S01G A02 Tetryzoline <0.0001 0.0257 0.0257 <0.0001 0.0229 0.0230 S01G A05 Phenylephrine - 0.0109 0.0109 - 0.0097 0.0097 S01G A51 Naphazoline, combinations 0.0008 0.3546 0.3554 0.0006 0.3716 0.3722

S01G X Other antiallergics 0.0239 0.0906 0.1145 0.0131 0.0889 0.1020 S01G X01 Cromoglicic acid 0.0169 0.0534 0.0703 0.0083 0.0544 0.0627 S01G X06 Emedastine - 0.0030 0.0030 <0.0001 0.0025 0.0025 S01G X08 Ketotifen - 0.0048 0.0048 - 0.0038 0.0038 S01G X09 Olopatadine 0.0070 0.0225 0.0295 0.0048 0.0228 0.0276 S01G X10 Epinastine - 0.0069 0.0069 - 0.0055 0.0055

Table 16.8 Local anaesthetics for ophthalmological system, S01H (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01H Local anesthetics 0.0333 0.0292 0.0625 0.0287 0.0297 0.0584

S01H A Local anesthetics 0.0333 0.0292 0.0625 0.0287 0.0297 0.0584 S01H A03 Tetracaine 0.0001 0.0010 0.0011 <0.0001 0.0009 0.0010 S01H A04 Proxymetacaine 0.0332 0.0282 0.0614 0.0287 0.0287 0.0574

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Table 16.9 Ophthalmic surgical aids, S01K (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01K Surgical aids 0.3797 0.3712 0.7509 0.6640 0.5443 1.2083

S01K A Viscoelastic substances 0.3797 0.3712 0.7509 0.6640 0.5443 1.2083 S01K A01 Hyaluronic acid 0.0039 0.0828 0.0867 0.0037 0.1830 0.1867 S01K A02 Hypromellose 0.3758 0.2884 0.6642 0.6603 0.3612 1.0215 S01K A51 Hyaluronic acid, combinations - <0.0001 <0.0001 - <0.0001 <0.0001

Table 16.10 Ocular vascular disorder agents, S01L (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01L Ocular vascular disorder 0.0001 0.0006 0.0007 0.0001 0.0007 0.0008 agents

S01L A Antineovascularisation agents 0.0001 0.0006 0.0007 0.0001 0.0007 0.0008 S01L A01 Verteporfin <0.0001 0.0002 0.0003 0.0001 0.0002 0.0003 S01L A04 Ranibizumab <0.0001 <0.0001 0.0001 <0.0001 0.0001 0.0001 S01L A05 Aflibercept <0.0001 0.0003 0.0004 <0.0001 0.0004 0.0004

Table 16.11 Other ophthalmological agents, S01X (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S01X Other ophthalmologicals 0.0015 0.0207 0.0222 0.0010 0.0164 0.0174

S01X A Other ophthalmologicals 0.0015 0.0207 0.0222 0.0010 0.0164 0.0174 S01X A18 Ciclosporin 0.0015 0.0207 0.0222 0.0010 0.0164 0.0174 S01X A22 Ocriplasmin - <0.0001 <0.0001 - <0.0001 <0.0001

Table 16.12 Otological preparations, S02 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S02A Antiinfectives 0.1584 0.0187 0.1771 0.1379 0.0261 0.1640

S02A A Antiinfectives 0.1584 0.0187 0.1771 0.1379 0.0261 0.1640 S02A A01 Chloramphenicol 0.1487 0.0047 0.1534 0.1276 0.0074 0.1349 S02A A16 Ofloxacin 0.0097 0.0076 0.0173 0.0103 0.0094 0.0197 S02A A30 Antiinfectives, combinations - 0.0064 0.0064 - 0.0093 0.0093

S02C Corticosteroids and 0.0010 0.0388 0.0398 0.0008 0.0392 0.0400 antiinfectives in combination

S02C A Corticosteroids and 0.0010 0.0388 0.0398 0.0008 0.0392 0.0400 antiinfectives in combination S02C A03 Hydrocortisone and 0.0010 0.0388 0.0398 0.0008 0.0392 0.0400 antiinfectives

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Table 16.13 Ophthalmological and otological preparations, S03 (Utilisation in DDD/1,000 inhabitants/day) ATC code Drug/Chemical substance 2015 2016 Public Private Total Public Private Total

S03A Antiinfectives 0.0041 0.0933 0.0975 0.0031 0.0916 0.0948

S03A A Antiinfectives 0.0041 0.0933 0.0975 0.0031 0.0916 0.0948 S03A A06 Gentamicin 0.0041 0.0933 0.0975 0.0031 0.0916 0.0948

S03C Corticosteroids and 0.0524 0.8079 0.8603 0.0458 0.7244 0.7702 antiinfectives in combination

S03C A Corticosteroids and 0.0524 0.8079 0.8603 0.0458 0.7244 0.7702 antiinfectives in combination S03C A01 Dexamethasone and 0.0397 0.7448 0.7845 0.0401 0.6650 0.7051 antiinfectives S03C A06 Betamethasone and 0.0127 0.0631 0.0758 0.0057 0.0594 0.0651 antiinfectives

Utilisation of ophthalmological agents 16.2 Shamala Retnasabapathy, Jamalia Rahmat, Vanitha Ratnalingan

In ophthalmology, defined daily dose (DDD) has been assigned for antiglaucoma preparations only.1 For the purpose of this report, the above standard has been applied to all ophthalmologicals.

Antiinfectives

The commonest antiinfective used in 2015 and 2016 was chloramphenicol followed by combination antibiotics of which, many contained combinations of neomycin or polymyxin B with other antibiotics. The most frequently used fluoroquinolone was moxifloxacin. However, an increasing trend of usage of levofloxacin was seen from 2014 (0.0012 DDD/1,000 inhabitants/day) to 2016 (0.0122 DDD/1,000 inhabitants/day).2

Antiinflammatory

Antiinflammatory ophthalmologicals can be either corticosteroids or non-steroids. Corticosteroids were more commonly used with dexamethasone most prescribed. With regards to non-steroids, nepafenac was more commonly used compared to ketorolac and showed an increasing trend from 2014 (0.0297 DDD/1,000 inhabitants/day) to 2016 (0.0362 DDD/1,000 inhabitants/day).2 The use of combination antiinflammatory agents and antiinfectives has shown a reduction from 2014 (0.2244 DDD/1,000 inhabitants/day) to 2016 (0.1704 DDD/1,000 inhabitants/day).2

Antiglaucoma

Antiglaucoma ophthalmologicals were the commonest of all preparations prescribed. Of these, beta blocking agents were most frequently used especially timolol and timolol combinations. This was followed by prostaglandin analogues of which latanoprost showed an upward going trend.

Decongestants and antiallergics

Decongestants and antiallergics were more commonly used in the private sector with naphazoline and/or naphazoline combinations being used most frequently.

Ocular vascular disorder agents

The usage of antineovascularisation agents has remained similar between 2015 and 2016. Aflibercept was the most commonly used.

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In conclusion, antiglaucoma agents remained the most widely used ophthalmologicals. Among the antiinfectives, levofloxacin showed an upward going trend.

Utilisation of otological agents 16.3 Siti Sabzah Mohd Hashim, Abd Razak Ahmad, Zulkiflee Salahuddin, Iskandar Hailani, Amran Mohamad, Jothi Shanmuganathan, Halimuddin Sawali, Leow Wooi Leong

Otological preparations used in Malaysia are classified into local antiinfectives ear drops, local corticosteroid ear drops and combination of antiinfectives and corticosteroid ear drops. There are two types of otological drugs that are mainly used, corticosteroid and antiinfective preparations. The most widely used antiinfective is chloramphenicol which is easily available in peripheral government clinics and private general practitioners.

REFERENCES

1. Guidelines for ATC Classification and DDD Assignment 2019; WHO Collaborating Centre for Drug Statistics Methodology: Oslo, Norway, 2018. 2. Malaysian Statistics on Medicines 2011-2014; Pharmaceutical Services Division, Ministry of Health Malaysia: Kuala Lumpur, 2017.

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17 Various Therapeutic Products

Statistics on other therapeutic products 17.1

Table 17.1 Statistics on other therapeutic products, V03, in public and private sector (Utilisation in DDD/1,000 inhabitants/day) ATC code Therapeutic group/ 2015 2016 Drug/Chemical substance Public Private Total Public Private Total

V Various 0.0281 0.0117 0.0398 0.0276 0.0135 0.0411

V03 All other therapeutic products 0.0281 0.0117 0.0398 0.0276 0.0135 0.0411

V03A All other therapeutic products 0.0281 0.0117 0.0398 0.0276 0.0135 0.0411

V03A E Drugs for treatment of 0.0185 0.0097 0.0282 0.0168 0.0111 0.0279 hyperkalemia and hyperphosphatemia V03A E01 Polystyrene sulfonate 0.0082 0.0008 0.0090 0.0084 0.0011 0.0095 V03A E02 Sevelamer 0.0030 0.0041 0.0072 0.0037 0.0054 0.0091 V03A E03 Lanthanum carbonate 0.0072 0.0048 0.0120 0.0047 0.0046 0.0093

V03A F Detoxifying agents for 0.0096 0.0019 0.0116 0.0108 0.0023 0.0132 antineoplastic treatment V03A F03 Calcium folinate 0.0096 0.0019 0.0116 0.0108 0.0023 0.0132

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