The Caribbean Public Health Agency is the Caribbean region’s collective response to strengthening health systems and addressing public health challenges which threaten development.

To obtain additional information, please contact: Caribbean Public Health Agency (CARPHA) 16-18 Jamaica Boulevard Federation Park Port of Spain, Trinidad and Tobago Tel: 868-299-0895 Fax: 868-622-2792 Email: [email protected] Website: http://carpha.org/

Suggested citation.

Caribbean Public Health Agency. Access to essential diabetic medicines. Organisation of Eastern Caribbean States, editor. Guidelines for the Management of Diabetes in Primary Care in the Caribbean; Vol. 4. Port of Spain: CARPHA; 2019.

ISBN 978-976-8114-54-9

© Caribbean Public Health Agency 2019 Module 5 Systems for Monitoring

CARPHA Guidelines Module 4 For Management Module 1 Access To of Diabetes In Evidence-Based Essential Medicines Primary Care In The Treatment Protocols Caribbean for Diabetes

Module 3 Guidance For Module 2 Persons With Healthy Lifestyle Diabetes (PwD) & Counselling Caregivers Contents

6 List of Tables 7 List of Appendices 8 List of Abbreviations 11 Preface 13 Acknowledgements 15 CARPHA Diabetes Guidelines: The Modular Approach Expanded 18 The Client-Centred Approach to Chronic Care 21 Introduction

23 Section 1: Medicines Used in the Treatment of Diabetes

24 Access to Essential Diabetic Medicines 27 Oral Lowering Agents 29 for Type 2 Diabetes Mellitus 32 Pharmacovigilance

34 Section 2: Supply Management

35 Introduction

35 Medicine Supply Chain Management 36 Selection 36 Procurement 37 Inventory Management 38 Standard Re-ordering Formulas 39 Pricing 39 Storage 40 Supply During Disasters 42 Reference List 50 Appendices

5 List of Tables

17 Table A: Modules of the Guidelines for the Management of Diabetes in Primary Care

26 Table 1: Profile of presently Available Glucose Lowering Agents Not including Insulin

28 Table 2: Risks and Benefits of Common Glucose Lowering Agents

30 Table 3: Types of Insulin Available

31 Table 4: Risk of Insulin

31 Table 5: Pharmacokinetic Properties of Insulin Products

6 List of Appendices i Adverse Reporting Form ii Quantification Exercise: Consumption Method

7 List of Abbreviations

ACE Angiotensin Converting Enzyme

ACEI ACE inhibitors

ADA American Diabetes Association

AER Albumin Excretion Rate

ARB Angiotensin Receptor Blockers

BMI Body Mass Index

CARPHA Caribbean Public Health Agency

CCFP Caribbean College of Family Physicians

CRS Caribbean Regulatory System

CVD Cardiovascular Disease

DCCT Diabetes Control and Complications

DKA Diabetic Ketoacidosis

DKD Diabetic Disease

DM Diabetes Mellitus

DPN Distal Symmetric Polyneuropathy

8 DPP-4 Dipeptidyl Peptidase 4 Inhibitor

EMB Evidence Based Medicine

EML Essential Medical List

ESRD End Stage Renal Disease

FBS Fasting Blood Sugar

GDM Gestational Diabetes

GLP-1 Glucagon like Peptide 1 Receptor Agonist

GMP Good Manufacturing Practice

HBA1c Glycosylated Haemoglobin

HHS Hyperglycaemic Hyperosmolar Syndrome

IDF International Diabetes Federation

IGT Impaired Glucose Tolerance

IFG Impaired Fasting Glucose

Meds Medications/Medicines

NCD Non-Communicable Disease

NGSP National Glycohemoglobin Standardization Program

9 OECS Organisation of Eastern Caribbean States

OGTT Oral Glucose Tolerance Test

PCP Primary Care Physician

PWD Persons with Diabetes

OECS PPS OECS Pharmaceutical Procurement Service

RPG Random Plasma Glucose

T2DM Type 2 Diabetes Mellitus

TZDs

UHC Universal Health Coverage

WDF World Diabetes Foundation

WHO World Health Organization

WINDREF Windward Islands Research and Education Foundation

10 Preface

The CARPHA Guidelines on the Management of Diabetes in Primary Care in the Caribbean provide a strategic approach to improving diabetes health outcomes, by providing simple directives on key aspects of care for persons with diabetes (PWD).

In 2018, the OECS Health Unit, as part of the Strategic Pillar ‘Healthy Environments and Health Empowerment,’ and consistent with the emphasis placed on Non-communicable Diseases (NCDs) in the region, collaborated with CARPHA and WINDREF and secured funding from the World Diabetes Foundation for the implementation of the “OECS Diabetes, Prevention and Care Project.” A key component of the project, required to support its implementation, was the updating of clinical practice guidelines for the management of diabetes. The collaborators viewed this project as opportune, as it allowed for the review and update of the CARPHA Management of Diabetes in Primary Care in the Caribbean.

Previous versions of these guidelines were produced in 1995, 1998 and 2006. However, with rapid advancements in research, resulting in new international guidelines and treatment protocols, there was a need for an updated document to be produced. Consistent with its remit to provide an accurate, timely and relevant evidence-base for public health decision-making, the Caribbean Public Health Agency teamed up with the Organisation of Eastern Caribbean States to expedite the production of the revised guidelines, aligning them with current WHO strategies on Non-communicable Disease (NCD) treatment and management, including the WHO HEARTS and WHO’s Package of Essential Package of Non-communicable Disease Interventions (WHO PEN).

11 High-quality, evidence-informed clinical practice guidelines bridge the gap between policy, best practice, local contexts and client choice. They have been upheld as an essential part of quality medical practice and have been defined as ‘a convenient way of packaging evidence and presenting recommendations to health care decision makers,’ improving effectiveness and quality of care, by standardising clinical practices, and reducing costly and preventable mistakes and adverse events.

This newest version of the CARPHA guidelines has been extensively modified from its previous format and uses a modular approach which includes five modules.

● Module 1: EVIDENCE-BASED TREATMENT PROTOCOLS ● Module 2: GUIDING LIFESTYLE CHANGES ● Module 3: GUIDANCE FOR PERSONS WITH DIABETES (PWD) AND CAREGIVERS ● Module 4: ACCESS TO ESSENTIAL MEDICINES ● Module 5: SYSTEMS FOR MONITORING

These modules are intended for use by clinicians, caregivers, policymakers and programme managers. Each one focuses on complementary aspects of care of diabetes in the health system, and targets different cadres of workers and care providers for management of diabetes. Target users may vary, based on context, existing health systems and national priorities in CARPHA Member States, and recommendations made in each of the modules may require adaptation for implementation at country level. Ultimately, the revised guidelines seek to support the efforts of Ministries of Health, to strengthen and standardise the management of diabetes in primary care and improve outcomes in care of diabetes, regionally.

12 Acknowledgements

The Caribbean Public Health Agency and the Organisation of Eastern Caribbean States acknowledge, with appreciation, the World Diabetes Foundation (WDF) and the several regional individuals and agencies whose contributions were indispensable to the successful completion of these revised guidelines:

Dr. Avery Hinds and Dr. Lisa Monrose, the Consultants who were instrumental in the development of this revised document.

The members of the CARPHA Expert Working Groups:

WORKING GROUP 1:

Prof. Surujpal Teelucksingh - UWI, St. Augustine • Dr. Michael Boyne - UWI, Mona • Dr. Marshall Tulloch-Reid – UWI, Mona • Dr. Sonia Roache-Barker - Caribbean College of Family Practitioners (CCFP) • Prof. Nigel Unwin - UWI, Cave Hill • Dr. Claude Khan – Ministry of Health Trinidad and Tobago

WORKING GROUPS 2 AND 3:

• Ms. June Holdip - Registered Dietitian • Ms. Alecia Surujlal - Registered Dietitian, Diabetes Educator • Ms. Jochelle Mohammed - Registered Dietitian

13 • Ms. Vanesa Martina - Public Health Nutritionist • Ms. Denesia Venus - Registered Dietitian and Public Health Nutritionist

The technical persons who assisted in the provision of materials, development of various modules, editing and revision including:

• CARPHA Technical Officers - .Dr Kimberly Ashby-Mitchell, Dr. Virginia Asin-Oostburg, Dr. Cheryl Jones, Dr. Glennis Andall- Brereton, and Ms. Christine Bocage • OECS Health Unit Staff - Ms. Lydia Atkins, Dr. Carlene Radix, and Ms. Eliza James • OECS Pharmaceutical Procurement Service Unit - Mr. Francis Burnett and Mr. Abraham Weekes • WINDREF - Professor Calum MacPherson and Dr. Satesh Bidaisee • Ministry of Health Saint Lucia - Dr. Christy Nathaniel and Ms Ira Isaac • Dr. Rohan Maharaj - University of the West Indies • Ms. Anica Sanoir – Caribbean Certified Diabetes Educator • Health Professionals, who participated in the peer review consultations • Mr. Sherlan Gittens, responsible for the graphics and layout of the guidelines

14 CARPHA Diabetes Guidelines: The Modular Approach Expanded

The revised CARPHA Guidelines take a modular approach to providing guidance on the Management of Diabetes in Primary Care in the Caribbean.

Module 1: EVIDENCE-BASED TREATMENT PROTOCOLS Targets primary care physicians, nurse-practitioners and any other health care provider who is directly involved in the medical management of diabetes. This module aims to give updated algorithms on care, incorporating the most recent recommendations in the care of diabetes.

Module 2: GUIDING LIFESTYLE CHANGES Intended for all persons on the health team, who provide care and lifestyle-counselling to persons living with diabetes (PWD). It is specifically geared toward physicians, dietitians, nutritionists, nurses, community aides and home-help. This module covers all aspects of lifestyle that directly impact target outcomes. Therefore, diet, physical activity, weight management and mental health are addressed in this module.

Module 3: GUIDANCE FOR PERSONS WITH DIABETES (PWD) AND CAREGIVERS Aims to inform to persons living with diabetes (PWD) and all persons involved in their care, with or without a medical or health care background. This module should be particularly useful to community nurses, home-help, community aides, and other community caregivers,

15 especially those involved in caring for PWD in their homes and can serve as a directory of topics relevant to caregivers. It addresses topics such as foot care, self-monitoring of blood glucose, identification and management of low blood glucose (hypoglycaemia) and high blood glucose (hyperglycaemia).

Module 4: ACCESS TO ESSENTIAL MEDICINES Targets physicians, nurses, pharmacists and personnel involved in ensuring the efficiency of health system procurement mechanisms. It provides information on the various classes of medicine available for care of diabetes, issues related to their availability, as well as the risks, benefits and cautions that should be considered in their use.

Module 5: SYSTEMS FOR MONITORING Targets all health care providers but is of particular relevance to Primary Care Managers and those involved in health systems evaluations. It focuses on monitoring and reporting information on the prevention and management of T2DM, and the implementation of the guidelines using standardised indicators and data collection tools.

Table I, below, summarises the scope and highlights the target users of each module.

16 Table A: Modules of The Guidelines for The Management Of Diabetes In Primary Care In The Caribbean

Modules of the Management of Diabetes in Primary Care Guidelines

ho are the target users Module hat does it cover Dietitians Physicians Nurses Pharmacist Carers Nutritionist

Module 1 Documentation of protocols vidence aimed at standardiing the ased clinical approach to the reatment management of 2DM in Protocols primary care.

Module 2 Information on lifestyle uiding interventions that target the Lifestyle four modifiable ris factors Changes for diabetes.

Module 3 Information for Persons ith uidance for Diabetes PD and lay PD and caregivers related to the Caregivers care of diabetes.

Information on medicines Module 4 and technologies available ccess to for diabetes management ssential and their supply-chain Medicines management at the primary care facility level.

Monitoring and reporting Module information standardied Systems for indicators and data collection Monitoring tools for use in the prevention and management of 2DM.

17 The Client-Centred Approach to Chronic Care

Diabetes is a chronic illness which extends across an individual’s lifespan. The goal of all clinicians and persons on the health team should therefore be to deliver optimal and evidence-based care and support. The Chronic Care Model, endorsed by PAHO/WHO, emphasises the importance of the team approach to the care of all Non-communicable Diseases (NCDs) and further underscores the integral role of high-level policy support in optimising the delivery of care to persons with chronic illnesses. This framework informs the approaches recommended in these guidelines and is both endorsed and encouraged by CARPHA and the OECS as a mechanism for improving the standard of health care delivered to people of the region.

The Chronice Car Model identifies patient-centeredness, effectiveness, efficiency, equity and timeliness as essential elements of efficient health service delivery for people with this chronic illness. From as early as the 1980’s, the approach to the care of “clients” has undergone a paradigm shift from the doctor-centred model, to one which gives more focus, autonomy and involvement to the recipient of health care services, initially called “patient-centred care.” Moria Stewart et al (2003, highlighted that persons receiving care preferred this model and reported improved satisfaction, outcomes, and health care utilisation with this approach. As archetypes, relating to health care delivery continued to evolve, and the shared role of health care providers and recipients in decision-making became more widely accepted, and the terminology describing health care participants was updated. “Patients” are now called “clients,” a term recognising the

18 more empowered role they play in their own health care. Rather than passively presenting to be “fixed” by a doctor, they are recognised as an integral part of the health care team for their treatment. These guidelines will therefore utilise the terms “persons with diabetes” (PWD) and “clients” in reference to the recipients of health care services for diabetes.

At each visit, health care providers need to remember that clients are individuals, with the circumstances of their lives constantly changing. The natural progression of the disease process also means that recommended management will almost certainly need to be adjusted periodically. Early involvement of the wider team of health professionals in the prevention and management of the complications of diabetes is a critical risk mitigation strategy, the success of which hinges upon the cooperation of educated, motivated clients and integrated, coordinated providers of health care. At each point of care, it behoves the care-provider, to seek an integrated understanding of the client’s world and to solicit feedback alongside the provision of their recommendations for improving management. Each member of the health team must recognise that managing the non-clinical (emotional, social, economic, psychological) needs and life issues of the client plays an important role in ensuring successful outcomes and must understand the relevance of tailoring their care to suit their individual clients.

Integrating the individual client-centred approach into the broader framework of the Chronic Care Model will, necessarily, take varying forms in different Member States and will require the adaptation of both systems and individuals to new ways of executing health care functions; but the benefits to be derived at both the individual and the systemic level from improving the quality of health care delivery have been shown, in many other jurisdictions greatly, to outweigh the costs.

19 MODULE 4 Access to Essential Medicines Introduction

The World Health Organization defines essential medicines as those that satisfy the priority health care needs of the population. They are selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost-effectiveness. Essential medicines are intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality and adequate information, and at a price the individual and the community can afford. The implementation of the concept of essential medicines is intended to be flexible and adaptable to many different situations; exactly which medicines are regarded as essential remains a national responsibility.

Reliable access to essential medicines and health products is dependent on an efficient procurement and supply management system. Consistently available, quality-assured, affordable medicines and technologies is a major strategy for reducing the burden of non-communicable diseases, such as diabetes.

The most common obstruction to the availability of essential medicines and technologies is poor supply chain management. Supply chains are able to deliver essential medicines and technologies as well as provide critical information to planners and policy-makers regarding demand and consumption. Medicines and technologies need to be managed appropriately to ensure that the correct medicines are selected, procured in the right quantities, distributed to facilities on time, and handled and stored in a way that maintains their quality.

21 This is supported by policies that enable sufficient quantities to be procured in order to reduce cost inefficiencies, ensure the reliability and security of the distribution system, and encourage the appropriate use of these health products.

Effective supply chain management avoids stock-outs and the disruption of treatment. It is dependent on timely procurement, continuous performance monitoring and prompt action in response to problems that may arise. Additionally, medicines must be dispensed correctly and used rationally by the healthcare providers and patients.

This module focuses on access to essential medicines for diabetes management, and includes:

• information on the pharmaceutical management cycle and policies; • selection of appropriate medicines; • supply-chain management, including quantification, forecasting, distribution, storage and handling; and • ensuring supply and accountability.

Pharmaceutical management requires continuous support, including policies and legislative frameworks and the country specific regulatory authority. In countries with no regulatory authority, procurement agencies should prequalify suppliers and manufacturers to ensure medicines are manufactured to international standards and Good Manufacturing Practice (GMP). Countries should also consider medicines approved by the Caribbean Regulatory System (CRS),which is a function which is under the aegis of the Caribbean Public Health Agency (CARPHA).

22 Section 1: Medicines Used in the Treatment of Diabetes Access to Essential Medicines for the Treatment of Diabetes There are several classes of medicine that are now used worldwide, in the treatment of diabetes. WHO Second and Third line Medicine in Diabetes Mellitus Care, and IDF 2017 Recommendations For Managing Type 2 Diabetes In Primary Care along with numerous other studies, suggest that should be the first drug to be chosen in the care of PWD. It can be given as monotherapy along with lifestyle changes to newly diagnosed persons with diabetes. To achieve greater client tolerance to the drug, start low and go slow. Recommended start 500mg daily and increase to 2000mg. Slow-release or modified release metformin can also be used if having significant gastrointestinal side effects. At present the modified release metformin is not available through the OECS but a Start low and go slow to supplier has been identified and achieve greater client tolerance to prescribed discussions are ongoing to add it to the medicines! formulary. If metformin is not tolerated or Recommended start 500mg adequate blood glucose control is not daily and increase to 2000mg. obtained with monotherapy, then advance to dual therapy by adding another glucose lowering drug (Module 1, Algorithm 2). If weight loss is a major issue, options that promotes weight loss should be considered. Newer classes of the glucose lowering medicines GLP-1 (Glucagon like peptide) or SGLT-2 (sodium- glucose-co-transporter Type 2 inhibitors), are recommended as they are associated with promoting weight loss.

The use of sulphonylureas continues to remain a second line of treatment in the Caribbean, because of the low cost of these medications. WHO supports its use from a public health standpoint, for that same reason. However, the first generation sulphonylureas such as and , should be avoided in older adults because of the increased risk of hypoglycaemia.24 Class of Drug Drug M fficacy Cost

Metformin epatic glucose output igh Low iguinide 200080mg Delays glucose absorption

Insulin release liclaide Sulphonylurea 30mg MR tab Maor complication is 2nd 60mg SR tab igh Low hypoglycaemia esp in eneration lyburide first generation

Meglitinides igh glinides Insulin Release

lpha Intestinal lucosidase carbose absorption of Moderate inhibitors carbohydrates

Ds Rosiglitqaone Insulin sensitivity igh Moderate hiaolidinedions Pioglitaone

nhances insulin DPP-4 inhibitors secretion in response dipeptidyl ildagliptin to meals Intermediate igh peptidase-4 Saagliptin lucagon secretion inhibitors logliphin lucose dependant

ugments insulin secretion after meal ingestion LP-1 enatide Suppresses glucagon igh igh Receptor gonist enatide R release Reduces hepatic glucose production

SL-2 Reduce plasma glucose Canaglifloin inhibitors by inducing glycosuria Dapaglifloin Sodium-glucose (Thus major Intermediate igh mpaglifloin Cotransporters complication is urinary Ipraglifloin ype 2 tract infection) Inhibitors

25 Class of Drug Drug M fficacy Cost

cts by a hepatic ile cid Colesevelam mechanism in ery igh sequestrants decreasing hepatic glucose output

lucagon mylin secretion slows ery igh mimetics gastric emptying

Table 1: Profile of presently available glucose lowering agents not including Insulin

Physicians are encouraged to customize prescribing, by considering the patient’s profile (age, weight, and any complications that pre- exist). The risk and benefits of each glucose lowering medication should also be considered before prescribing. (Tables 2 and 4). Combinations of different classes of medicine, with different mechanisms of action, are frequently AVOID first generation sulphonylureas such as required for optimum control. With so gl many returning nationals and tourists who ibenclamide, due to high associated risk of visit our shores with the medicines they hypoglycaemia! have been prescribed in their home countries primary care physicians must be aware of global trends and recommendations whilst providing to clients in limited resource settings. The current cost of newer medicine in the Caribbean such as (TZDs), and DPP-4 inhibitors, may be prohibitive in some cases.

Chlorpropamide and glibenclamide, both long-acting sulphonylureas are no longer recommended. Where still available, it should be used with extreme caution in the elderly and should be avoided in those with renal disease. It is the suggestion of these guidelines that it should be taken off the formulary to diminish risks to our population.

26 (a dopamine-2 agonist), which is outdated in its use as a glucose lowering drug as well as alpha glucosidase inhibitors such as arcabose have been discontinued in several OECS territories, because of their relatively limited effect on the lowering of HbA1c.

Oral Glucose Lowering Agents

Therapy with oral agents should be introduced simultaneously with diet and exercise. The majority of PWD will eventually require drug therapy in increasing dosages and often in multiple drug regimens as Type 2 Diabetes Mellitus (T2DM) is a progressive disorder. Many persons will also subsequently require the addition or substitution of insulin to achieve glycaemic control. T2DM, may require insulin for control at the time of diagnosis, if the patient is very symptomatic and/or has severe hyperglycaemia or high HbA1c of >11.0%.

The therapeutic options for the treatment of T2DM are:

• - increases insulin sensitivity; • Thiazolidinediones- increases insulin sensitivity; • - increases insulin release; • Meglitinides- increase insulin release; • Alpha-glucosidase inhibitors - modifies intestinal absorption of carbohydrates; • Dipeptidyl-peptidase 4 Inhibitors (DPP-4 inhibitors) - augments the release of insulin;

27 Medicine ypo eight I Side Maor Chronic ther Chronic ffects C eart Side idney vents Failure ffects Disease S3

Reduce Slight dose in 3 Metformin Neutral Moderate enefit Neutral Nil loss Contraindicated in 34

Moderate Caution high ris hypo stg3 Sulphonylurea ain Neutral Neutral Neutral Nil Contraindicated Severe ecept glipiide 1st en and glicaide

dema Pioglitaone Neutral ain Neutral Neutral Ris and one Neutral loss

Neutral stage lpha- 3 3 lucosidase Neutral Neutral Moderate Neutral Neutral Nil Inhibitors Contraindicated stage 4

Pancreatitis Neutral but DPP4- must reduce Neutral Neutral Neutral Neutral Neutral Inhibitors dose ecept eart failure not a class effect

Caution with LP1 eenatide R enefit age Receptor Neutral Loss Moderate Neutral Nil st 3 3 2RC gonists Contraindicated stage 4

Mycotic genital SL2 Neutral Loss Neutral enefit Neutral infections Contraindicated Inhibitors fractures stage 3 amputation

Table 2: Risks and benefits of common glucose lowering agents 28 • Glucagon-like, Peptide -1 receptor agonist (GLP-1 receptor agonist) - enhances glucose-stimulated insulin, biosynthesis and secretion, suppresses post-prandial glucagon release, decreases appetite and food intake, delays gastric emptying; • Sympatholytic dopamine-2 agonist: cycloset (bromocriptine mesylate) - inhibits excessive sympathetic tone within the central nervous system resulting in a reduction in post meal plasma glucose; • Sodium-Glucose-co-transporter-2 Inhibitors (SLGT-2) – reduces plasma glucose concentration by inducing glycosuria; • - replaces insulin deficiency.

Table 3 looks at the risks and benefits of the oral glucose lowering agents available for treatment of diabetes.

Insulin for Type 2 Diabetes Mellitus

Insulin is indicated in all persons with Type 1 diabetes mellitus and Type 2 diabetes mellitus, who don’t achieve control on oral diabetic medicine. There are several types of insulin presently available as indicated in the table below (Table 4). The newest being the ultra-lente insulin which is concentrated and has very long half- life. The main side effects of insulin are hypoglycaemia and weight gain but its use poses no risk of CVD (Table 5).

29 Type of Insulin Examples

I Rapid acting nsulin glulisine

Short acting uman Regular

Intermediate uman NP Intermediate acting Neutral agedon

Long-acting largine asal Insulins Detemir ltralente

Pre-mied 70 30 NP Regular 80 20 Lente Regular

iphasic Insulin 7 Protamine Lispro 2 Insulin Lispro

Concentrated -00

Table 3 Types of insulin available

30 eight CV Effects Renal Effects Change

Insulin es ain Neutral Neutral

Table 4: Risks of insulin

Insulin Type Onset Peak Duration

Rapid-acting or -1min 4-90min 2-4h analogue Lisproaspart glulisine

Short-acting 0.-1h 2-4h 4-8h regular

NP insulin 1-3h 4-10h 10-18h

Detemir 1-2h None 12-24h

largine 2-3h None 20-24h

Premied Insuline

70 NP 30 0.-1h 2-10h 10-18h regular

0 NP0 0.-1h 2-10h 10-18h regular

7 NPL 2 10-20min 1-6h 10-18h lispro

0 NPL0 10-20min 1-6h 10-18h lispro

70 NP30 10-20min 1-6h 10-18h aspart

Table 5 Pharmacokinetic properties of insulin products

31 Pharmacovigilance

The World Health Organization (WHO) has defined pharmacovigilance as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problem. An adverse drug reaction is any noxious change which is suspected to be due to a medicinal product, occurs in doses normally used by humans, requires treatment or decrease in dose or indicates caution in the future use of the same drug.

The aims of pharmacovigilance is described below (WHO 2002): • improve patient care and safety in relation to the use of medicines and all medical and paramedical interventions; • improve public health and safety in relation to the use of medicines; • detect problems related to the use of medicines and communicate the findings in a timely manner; • contribute to the assessment of benefit, harm, effectiveness and risk of medicines, leading to the prevention of harm and maximization of benefit; • encourage the safe, rational and more effective (including cost-effective) use of medicines; and • promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public.

An adverse event reporting consists of four elements: 1. An identifiable patient 2. An identifiable reporter 3. A suspect medicine 4. A suspected adverse event

32 OECS/PPS has implemented a regional adverse reaction form which health care workers can submit by post or online to OECS/PPS (Appendix I). Moreover, OECS adverse reaction forms are subsequently channelled to Vigicarib, the Caribbean network located at CARPHA, Trinidad, which finally deposits the reports into Vigibase, the global WHO Pharmacovigilance Centre in Uppsala, Sweden.

Physicians are encouraged to report any adverse effects reported by patients on the website: https://carpha.org/What-We-Do/CRS/ VigiCarib

33 Section2: Supply Management Introduction

A holistic approach needs to be taken in trying to reduce the impact of diabetes through prevention, diagnosis, care and management. A key component is having a list of essential medications that are affordable and easily available when required. An essential list of medicines allows for easier procurement of the correct quantities thus avoiding shortages. Systems must always be put in place for the correct handling, storage and distribution of medicines in a manner that does not compromise the integrity of the medications.

Medicine Supply Chain Management

Medicine Supply Chain Management (MSCM) is a critical component

Selection

g u n a i li ib fi r c c a s t i e o r n

P

ccess to

t D Medicines n

i s e

t r m ib e

u r

u

t io c

n ro

P

arehouse

Figure 1: Supply Chain Management Cycle

35 in managing diabetes to ensure patients have regular access to quality medicines at competitive prices. The important components of supply chain management are illustrated in figure 1.

Selection

The cornerstone of an efficient pharmaceutical supply system is the selection of cost-effective medicines to be available to prescribers and clients. Moreover, access to medicines is a basic human right. The advantages of a list of essential medicines are four- fold: drug therapy is improved, procurement is enhanced, purchasing power is strengthened and inventory holding cost is contained.

Procurement

An effective procurement process should encompass the following activities: • procuring the right drugs in the right quantities; • obtaining the lowest possible purchase price; • ensuring that all drugs procured meet recognized standards of quality; • arranging timely delivery to avoid shortages and stock-outs; • ensuring supplier reliability with respect to service and quality; and • setting the purchasing schedule and formulas for inventory control.

Given the impact of procurement activities on the operation and

36 effectiveness of health services, it is critical that these activities be performed by trained staff using sound procedures, and with access to reliable inventory and consumption information.

Inventory Management

Inventory management is central to an efficient pharmaceutical supply, because proper inventory management leads to an optimization of financial resources, consistent availability of vital supplies, and improvement in the quality of patient care. Supply systems usually maintain either a manual or electronic inventory system (Appendix VII).

Efficient inventory management systems incorporate objective decisions regarding order frequency and quantity, accurate stock records, and systematic performance monitoring. In these cases, there are systematic procedures and rules to guide staff, assisted by an understanding of the basic principles of effective inventory management. To implement good inventory management, procurement staff must use mathematical formulas as models to set policies for stock levels, re-order frequency, and re-order quantity. Several simple formulas have been developed to calculate the various parameters of inventory control.

The ideal inventory control model is shown in Figure 2. In this ideal model, supplies are issued in response to demand, and stock on hand steadily declines until an order is placed. The stock on hand consists of two components, the working stock and the safety stock (SS). In the ideal model, the supplier operates according to plan, the shipments arrive on time, the quantity ordered (Qo) is received, and the inventory level reverts to its starting maximum point. Working stock varies from zero to the quantity ordered, and represents the stock used to satisfy demand between deliveries.

37 SS0

0

verage Inventory oring Reorder Stoc Level Stoc on hand Safety SS Stoc Lead Lead ime ime Safety Stoc rder rder rder rder Placed Received Placed Received ime in Months

Figure 2: Ideal inventory control model

Standard Re-ordering Formulas

Using this approach, one defines a theoretical maximum stock for each item, to provide sufficient but not excessive stock to last between orders; minimum stock level or re-order level determines at what point an order should be placed. Safety stock should be included in the minimum stock level. Variables for consideration include: • Average monthly consumption, adjusted for stock-outs (CA); • Supplier lead time (LT); • Procurement period - time until the next order will be placed (PP);

38 • Safety stock - additional stock to cope with variability in consumption and lead time (SS), usually between 1 and 2 months of stock and • Stock on hand in inventory.

The equation of calculating the minimum stock (SMIN ) is: Minimum stock = (LT x CA) + SS

Maximum (target) stock level (SMAX ) can be calculated as the minimum stock plus the procurement period multiplied by the average consumption;

The Equation is:

SMAX = SMIN + (PP x CA)

Pricing

The price of essential medicines for the care of diabetes is an indication of the access to treatment for PWD. As a result of bulk purchasing medicines obtained from government health care facilities tends to be the most affordable to the clients. Economies of scale allow better value for money keeping medicines affordable.

Storage

It is essential for medicines and other relevant medical equipment to be stored in a manner that allows for optimal performance at

39 use. Adequate storage should also protect the physical stability and efficacy of the medication, so that it reaches clients in a stable condition. Many countries have central procurement units responsible not only for the purchasing of medicines but also adequate central storage. All central storage units provide a temperature controlled, dry environment for the medicines until they are dispensed to the local health centres. The health facilities must also have adequate dry, cool designated pharmacy areas for storage at the facilities. Special care is taken with insulins that need to follow a strict cold chain.

Systems for monitoring and evaluation are in place to ensure that there is a constant supply of required medications and that shortages do not occur.

Supply During Disasters

Consideration should be given to national comprehensive plans that speak to availability and distribution of medications during times of disaster. Ongoing efforts in the Caribbean region will specifically aim to answer these questions and develop disaster preparedness plans for distribution of medication. A minimum requirement of any such plan should be the implementation of back-up generators at the central procurement storage facilities to ensure that even in a disaster, the integrity of the medications in storage will not be affected by temperature changes and the cold chain for stored insulins will not be interrupted.

40

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52 Consumption Method

FACTORS

Lead-time (LT) = 3months

Procurement period (PP) = 12months

Monthly consumption (CA) = 100units of medicines

ASSIGNMENT Calculate

• Safety stock • Minimum Stock • Maximum Stock

Morbidity Method

FACTORS:

Daily dose of lopinavir ritonavir = two tablets two times a day

Length of treatment = 12 months

Number of patients = 200patients

ASSIGNMENT: Calculate the annual requirements for lopinavir ritonavir.

Appendix II: Quantification Exercise; Managing Drug Supply

53