MALAYSIAN STATISTICS ON MEDICINES 2007 USE OF GYNAECOLOGICALS, SEX HORMONES AND HORMONAL CHAPTER 12 | CONTRACEPTIVES J. Ravindran1, Nik Nasri2, Ghazali I.3, Wan Abu Bakar4, Tham S.W.5, J. Ravichandran6, Zaridah S.7, W. Zahanim W.Y.8, Intan S.S.1, Tan A.L.1 1. Kuala Lumpur Hospital 2. Universiti Sains Islam Malaysia 3. Sultan Ismail Hospital, Johor Bahru, 4. Sultanah Nur Zahirah Hospital, Kuala Terengganu, 5. Tuanku Ja’afar Hospital, Seremban 6. Sultanah Aminah Hospital, Johor Bahru, 7. Tuanku Fauziah Hospital, Kangar, 8. Kuala Krai Hospital There has been lack of a comprehensive review on the use of gynaecological, sex hormone and hormonal contraceptive drugs in the Malaysian literature.1 The use of gynaecological anti-infectives and antiseptics was 0.1976 DDD/1000 population/ day in 2007; other gynaecologicals was 0.0946 DDD/1000 population/day whereas sex hormones and modulators of the genital system showed a marked increase to 8.1348 DDD/1000 population/day. Overall usage of anti-infectives and antiseptics showed a slight decrease from the previous year. This may be due to the common antibiotics used in gynaecological practice being captured in other codes of the ATC Classification system. An example would be the total lack of data in the public hospital system and the insignificant use of metronidazole (G01A F01), which is a widely used antibiotic for anaerobic infections in gynaecological practice. The use of nystatin showed a marked reduction in both the public and private sector. On the other hand, the use of clotrimazole doubled due to its ease of use. There has been a significant reduction in the utilisation of methylergometrine and ergometrine, which are drugs used in the third stage of labour and in the management of post-partum haemorrhage.2,3 Misoprostol is a drug that is licensed for peptic ulcer disease but it has been used “off-label” in Obstetrics and Gynaecology (O&G) practice for cervical priming, termination of pregnancy, induction of labour and postpartum haemorrhage.4 There has been very little use of this drug in the public sector as it has not been included in the Ministry of Health Drug Formulary. However, its use in the private sector has increased from 0.0016 to 0.0027 DDD/1000 population/day. The data is not sufficient to clarify for which indication it has been used in the private sector. There is a role for considering its use in the medical management of miscarriage as evidenced by current O&G guidelines. Preterm labour complicates up to 15% of pregnancies.5 The majority of drugs used in labour suppression are used “off-label”. As such the burden of this complication and the drugs used in its management are not captured comprehensively in the NMUS; examples would be nifedipine, salbutamol and terbutaline. The use of the only registered drug for labour suppression, atosiban,5 was negligible. Bromocriptine was still the most prevalent prolactin inhibitor used. The use of cabergoline showed a decline in 2007 in both the public and private sectors. However, a reversal in this trend is to be expected in future due to worries of cardiovascular complications and the risk of concurrent use of antihypertensives with bromocriptine.6 Hormonal contraceptives for systemic use showed a marked increase in utilisation from 4.4113 to 5.8766 DDD/1000 population/day. This rise was contributed significantly by an increase in the usage of fixed combination progestogens and oestrogens, particularly levonorgestrel and oestrogen as well as drospirenone and oestrogen. In general, the use of progestogens decreased slightly from 0.8777 to 0.8691 DDD/1000 population/day. However, the usage of etonogestrel declined significantly from 0.4533 to 0.0651 DDD/1000 population/day. This decline was reflected in both public and private sector usage. This may have significant implications in the provision of effective contraception with regards to reduction of maternal mortality in high risk mothers. The usage of oestrogens more than doubled from 0.2309 to 0.5289 DDD/1000 population/day. This rise was due to an increase in both estradiol as well as conjugated oestrogen. Concerns about the implication of hormone replacement therapy and breast malignancy, may have led to the increased utilisation of tibolone seen in 2007. 7 The usage of gonadotropins and other ovulation stimulants showed a decline from 0.3619 to 0.3187 DDD/1000 population/day. This reduction is in contrast to the increasing number of centres providing Assisted Reproductive Technology. The majority of such centres are in the private sector and the response rate to the NMUS may have contributed to this apparent decline. There has been a near doubling in the usage of cyproterone and oestrogens. This may be due to the increased burden of polycystic ovarian syndrome (PCOS).8 Certain significant changes in prescribing patterns have been noticed in NMUS 2007 as compared to 2006. The reasons for these are not entirely clear. They may be due to an increasing disease burden, cost of drugs, availability of drugs in public sector prescribing systems, and the development of Clinical Practice Guidelines. Better quality data from the private prescribers is essential for meaningful analysis and trending for future reports. 62 63 MALAYSIAN STATISTICS ON MEDICINES 2007 CHAPTER 12 | USE OF GYNAECOLOGICALS, SEX HORMONES AND HORMONAL CONTRACEPTIVES Table 12.1 : Use of Gynaecologicals, Sex Hormones and Hormonal Contraceptives, in DDD/1000 opulation/day 2006-2007 ATC Drug Class 2006 2007 G01 Gynaecological anti-infectives and antiseptics 0.2124 0.1976 G02 Other gynecologicals 0.0731 0.0946 G03 Sex hormones and modulators of the genital system 6.3615 8.1348 Table 12.2.1 : Use of Gynaecologicals, Sex Hormones and Hormonal Contraceptives by Drug Class,in DDD/1000 population/day 2006-2007 ATC Drug Class 2006 2007 G01A Anti-infectives and antiseptics, excl. combinations with corticosteroids 0.2124 0.1976 G01A A Antibiotics 0.0648 0.0089 G01A C Quinoline derivatives - - G01A D Organic acids - - G01A F Imidazole derivatives 0.1476 0.1885 G01A G Triazole derivatives - - G01A X Other anti-infectives and antiseptics - 0.0001 G02A Oxytocics 0.0515 0.0408 G02A B Ergot alkaloids 0.0059 0.0022 G02A D Prostaglandins 0.0457 0.0386 G02C Other gynaecologicals 0.0215 0.0538 G02C A Sympathomimetics, labour repressants - <0.0001 G02C B Prolactine inhibitors 0.0215 0.0537 G02C X Other gynaecologicals <0.0001 <0.0001 G03A Hormonal contraceptives for systemic use 4.4113 5.8766 G03A A Progestogens and oestrogens, fixed combinations 2.6072 4.4199 G03A B Progestogens and oestrogens, sequential preparations 0.0388 0.0611 G03A C Progestogens 1.7654 1.3956 G03B Androgens 0.0267 0.0266 G03B A 3-oxoandrosten (4) derivatives 0.0245 0.0262 G03B B 5-androstanon (3) derivatives 0.0022 0.0005 G03C Oestrogens 0.2309 0.5289 G03C A Natural and semisynthetic oestrogens, plain 0.1336 0.4245 G03C B Synthetic oestrogens, plain - - G03C X Other oestrogens 0.0973 0.1045 G03D Progestogens 0.8777 0.8691 G03D A Pregnen (4) derivatives 0.3673 0.3689 G03D B Pregnadien derivatives 0.1996 0.1913 G03D C Estren derivatives 0.3108 0.3089 G03F Progestogens and oestrogens in combination 0.2108 0.2268 G03F A Progestogens and oestrogens, fixed combinations 0.0754 0.0544 G03F B Progestogens and oestrogens, sequential preparations 0.1354 0.1725 G03G Gonadotropins and other ovulation stimulants 0.3619 0.3187 G03G A Gonadotropins 0.0342 0.0211 G03G B Ovulation stimulants, synthetic 0.3277 0.2976 G03H Antiandrogens 0.0878 0.1421 G03H A Antiandrogens, plain 0.0130 0.0081 G03H B Antiandrogens and oestrogens 0.0748 0.1339 G03X Other sex hormones and modulators of the genital system 0.1544 0.1460 G03X A Antigonadotropins and similar agents 0.0251 0.0183 G03X C Selective oestrogen receptor modulators 0.1293 0.1277 64 65 CHAPTER 12 | USE OF GYNAECOLOGICALS, SEX HORMONES AND HORMONAL CONTRACEPTIVES MALAYSIAN STATISTICS ON MEDICINES 2007 Table 12.2.2 : Use of Gynaecologicals, Sex Hormones & Hormonal Contraceptives by Drug Class & Agents, in DDD/1000 population/day 2006-2007 ATC Drug Class and Agents Sector 2006 2007 G01A A Antibiotics Public 0.0596 0.0051 G01A A01 Nystatin Private 0.0040 0.0038 Total 0.0636 0.0089 Public - - G01A A03 Amphotericin B Private 0.0012 <0.0001 Total 0.0012 <0.0001 Public - - G01A A10 Clindamycin Private <0.0001 - Total <0.0001 - G01A C Quinoline derivatives Public - - G01A C03 Chlorquinaldol Private - - Total - - G01A D Organic acids Public - - G01A D03 Ascorbic acid Private - - Total - - G01A F Imidazole derivatives Public 0.0539 - G01A F01 Metronidazole Private 0.0003 <0.0001 Total 0.0543 <0.0001 Public 0.0216 0.0716 G01A F02 Clotrimazole Private 0.0585 0.1031 Total 0.0801 0.1747 Public - - G01A F04 Miconazole Private 0.0035 0.0059 Total 0.0035 0.0059 Public - - G01A F05 Econazole Private 0.0069 0.0064 Total 0.0069 0.0064 Public - - G01A F07 Isoconazole Private - - Total - - Public - <0.0001 G01A F08 Tioconazole Private 0.0024 0.0014 Total 0.0024 0.0015 Public - - G01A F11 Ketoconazole Private 0.0004 - Total 0.0004 - Public - - G01A F15 Butoconazole Private - <0.0001 Total - <0.0001 G01A G Triazole derivatives Public - - G01A G02 Terconazole Private - - Total - - 64 65 MALAYSIAN STATISTICS ON MEDICINES 2007 CHAPTER 12 | USE OF GYNAECOLOGICALS, SEX HORMONES AND HORMONAL CONTRACEPTIVES ATC Drug Class and Agents Sector 2006 2007 G01A X Other antiinfectives and antiseptics Public - <0.0001 G01A X03 Policresulen Private - <0.0001 Total - 0.0001 Public - - G01A X05 Nifuratel Private - - Total - - Public - - G01A X11 Povidone-iodine