Trends in antimalarial drugs prescribed in Australia 1992 to 1998

BRIEF COMMUNICATION

Trends in Antimalarial Drugs Prescribed in Australia 1992 to 1998 Peter A. Leggat and Richard Speare

The use of chemoprophylaxis decreases the severity and frequency of death from malaria due to Plasmodium falciparum compared with those who take no prophylaxis.1 Advice on the prevention of malaria has been deemed as among the most important to give travelers in Australia.2 Geographic knowledge of the distribution and prevalence of malaria and drug-resistant malaria should be used to base decisions concerning whether or not to give malaria chemoprophylaxis. Therapeutic guidelines, which include guidelines on malaria chemoprophylaxis, assist travel health advisers in their selection of antimalarials.3 Previous studies have suggested that considerable variation exists in patterns of antimalarials used in relation to the prevailing antimalarial guidelines in Australia.4,5 Little is known about the trends in the use of various antimalarial agents prescribed to travelers for the prevention and treatment of malaria,in Australia.The aim of this study was to investigate the trends in use of antimalarial drugs prescribed in Australia from 1992 to 1998. In Australia, between 1992 and 1998, nine drugs could have potentially been prescribed for

malaria. Four drugs (chloroquine, mefloquine, proguanil, pyrimethamine/dapsone) were most likely almost solely used as antimalarials. The remaining five drugs (hydroxychloroquine, quinine, pyrimethamine, pyrimethamine/sufadoxine, and doxycycline) had additional indications.The former group of drugs would be expected to be an accurate indicator of trends in antimalarial use, whereas the latter group would be a less accurate indicator of trends although other uses potentially could obscure prescriptions for antimalarial use. Methods In 2001, data was extracted from the Australian Statistics in Medicine reports published by the Pharmaceutical Benefits Advisory Committee, Drug Utilization Committee, on antimalarials used in Australia for t h ep e riod 1992 to 1998.6–12 The Pharmaceutical Benefits Advisory Committee, Drug Utilization Committee, of the Australian Government, collects official data on pharmaceutical use in Australia. Data was obtained on the antimalarials: quinine, mefloquine, chloroquine, hydroxychloroquine,proguanil,doxycycline, and products containing pyrimethamine. Primaquine use was not evaluated due to nonavailability of data;however, it was thought to be minimal. Antimalarial use was determined annually in prescribed courses. Trends in use were descriptively analyzed. The use of these antimalarials was compared with the prevailing published recommendations for malaria chemoprophylaxis. 2,3

Peter A. Leggat, FAFPHM, FACTM, FFTM, and Richard Speare, FAFPHM, FACTM, MACVS: School of Public Health and Tropical Medicine, James Cook University, Townsville, Queensland, Australia. The authors had no financial or other conflicts of interest to disclose.

Results

Disclaimer: The views expressed in this paper do not necessarily represent the views of the Commonwealth Department of Health and Aged Care or of any other organization referred to in this paper.

For the drugs solely used as antimalarials, prescriptions for the pyrimethamine-containing compounds declined markedly from 1992 to 1998 (Table),whereas use of mefloquine and proguanil increased. Of the group of antimalarials with other uses, the number of prescriptions for quinine increased whereas the other drugs declined (see Table).

Correspondence: Peter A. Leggat, Associate Professor, School of Public Health and Tropical Medicine, James Cook University, Townsville, Queensland, 4811 Australia. J Travel Med 2003; 10:189–191.

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J o u rn a l o f Tr a v e l M e d i c i n e , Vo l u m e 1 0 , N u m b e r 3

Table Number and Percentage Change of Prescriptions of Antimalarials by Year by Antimalarial in Australia, 1992 to 1998 Absolute Number of Prescriptions Antimalarial Chloroquine Hydroxychloroquine Chloroquine group Mefloquine Proguanil Quinine* Pyrimethamine Pyrimethamine1 Dapsone Pyrimethamine1 sulfadoxine Pyrimethamine group Doxycycline *

Percent Change from the Previous Year ( 1/2 %)

1992 (1995)

1993

1994

1995

1996

1997

1998

87,126 34,164 121,290 12,636 – 601,046 1,767

216 216 27 144 – 12 24

246 18 227 113 – 22 240

273 115 226 110 (267) 11 120

1112 255 226 226 1933 12 28

210 210 210 216 129 15 16

217 217 217 118 124 12 233

84,691

227

279

255

215

236

270

7,560 94,018 3,078,849

226 226 27

260 276 24

238 248 26

215 214 25

10 224 26

240 255 29

*

These drugs are used for indications other than malaria.

Discussion Some variability was seen in antimalarial use in this study, which appeared to be influenced at least in part by the prevailing Australian guidelines for malaria chemoprophylaxis.2,3 Similar variability in malaria chemoprophylaxis prescribed has been described previously in other countries.13,14 The use of summarized prescribing information is low cost and can be used to examine general trends in the use of antimalarials, particularly for the group of drugs rarely used for any other indication. For the group of drugs used for other purposes, the extrapolation to antimalarial use is difficult to make accurately.It also could not be determined from the data to what extent antimalarials were used for treatment as opposed to chemoprophylaxis;however, it was expected that the many imported cases of malaria were treated with quinoline derivatives.This study also did not address the issue of whether antimalarial use was relevant to all travelers,as it is known that almost a fifth of international travelers may be taking unnecessary chemoprophylaxis,15 hence only general trends in antimalarial use could be studied here. Quinine use remained reasonably steady in Australia, increasing by 1998 to 10.6%, the 1992 level. Quinine was the principal recommended treatment and standby treatment, alone or with doxycycline, for malaria due to Plasmodium falciparum in Australia throughout the period of the study.2 It is not known to what extent quinine was used for other purposes, such as night cramps. Mefloquine has been the mainstay of recommendations for chemoprophylaxis of travelers entering chloroquine-resistant areas.3 It has also been recommended as a drug of choice for standby treatment and treatment throughout the study period. 2 However, this increase was biphasic with a rise in use in 1993 followed

by a decline to a low level in 1997, with a second rise in 1998.The use of mefloquine was clarified in the 1995 recommendations.2 The controversy associated with the side effects of mefloquine, particularly in regard to its reported neuropsychiatric effects, its effect on dreaming, and other side effects,may be a contribution to some of the variability in the prescription of this antimalarial drug.3 In this study, Maloprim and Fansidar use was shown to have declined markedly because of the release of the updated guidelines in 1994.2 Maloprim and related drugs, such as pyrimethamine/sulfadoxine (Fansidar) and pyrimethamine (Daraprim), were removed from the list of recommended chemoprophylaxis, and their use has been advised against for Australians since 1994.2 The use of chloroquine and hydroxychloroquine combined declined in 1992. However, since hydroxychloroquine may have other uses apart from antimalarial use, interpretation is difficult for this particular drug. Resurgence in the use of chloroquine in 1995 to 1996, probably reflected prevailing malaria chemoprophylaxis guidelines that recommended a combination of chloroquine and doxycycline, also seen in New Zealand.14 The introduction of proguanil in 1995,which is usually given in combination with chloroquine, may have also contributed to its resurgence. However, its use as an antimalarial was probably mainly directed at treatment of patients with Plasmodium vivax infection. Proguanil was not recommended as a chemoprophylaxis for malaria in the 1994 guidelines.2 At that time, it was unavailable in Australia. Since its introduction in 1995, there has been a marked rise in the use of proguanil, which is normally given in combination with chloroquine. Since doxycycline is widely used for its antibacterial effect, it is impossible from this data to determine the extent of use of doxycycline as an antimalarial agent.

L e g g a t a n d S p e a r e , Tr e n d s i n A n t i m a l a r i a l D r u g s

Doxycycline was also used for a variety of indications, of which malaria treatment (with quinine) and chemoprophylaxis were probably minor components in Australia during the period of this study. The use of doxycycline has slowly declined from the 1992 baseline. Perceived problems with doxycycline as a chemoprophylactic agent,such as side effects like photosensitivity and gastro-intestinal upsets, the need to take it daily, and the fact that breakthrough parasitemia may occur, particularly if doses are missed, may also mitigate against it being used more frequently. The prescription of chloroquine plus doxycycline, as per the old Australian guidelines,2 was perhaps used to overcome the problem of resistance in P. falciparum, as well to effectively prevent P. vivax malaria. Conclusions This study has shown a marked fall in pyrimethaminecombination antimalarial drugs over the years 1992 to 1998, with a rise in mefloquine and proguanil. The prescribing in 1998 of 967 courses of Maloprim is of concern because there is now no justification for use of this combination as a chemoprophylactic agent. The issuing of updated national travel health guidelines appears to have been the most effective means of influencing the prescription of antimalarials, with considerable reduction in the use of antifolate drugs. Continuing medical education, compliance with the national travel medicine guidelines,and regulation of antimalarial use, especially through restricted access and withdrawal from the market, may be useful in maintaining appropriate prescription of antimalarial drugs.Where appropriate,advice concerning personal protective measures against malaria and other vectorborne diseases should continue to be given. Acknowledgments The assistance of Dr. Frances W. Leggat and also the Pharmaceutical Benefits Advisory Committee, Drug Utilization Committee, of the Commonwealth Health Department, is gratefully acknowledged. This project was partly supported by a Merit Research Grant,James Cook University.

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References 1. Lewis SJ, Davidson RN,Ross EJ, Hall AP.Severity of imported malaria:effect of taking antimalarial prophylaxis.BMJ 1992; 305: 741–743. 2. Commonwealth Department of Health. Health information for international travel, 1995. 4th Ed. Canberra: Australian Government Publishing Service, 1994. 3. Spicer J,Christiansen K, Currie B,et al. Therapeutic guidelines: antibiotic.Version 11.North Melbourne: Therapeutic Guidelines Limited, 2000. 4. McCall BJ, Pearce MC. Malaria treatment in Queensland, 1992.The use of malaria treatment guidelines.Med J Aust 1994; 161:259–262. 5. Gordon G. Malaria prophylaxis prescribing:is the message getting across? (Abstract).In:Speare R, Koehler J, Leggat PA. Proceedings of the Fifth Annual Scientific Meeting of The Australasian College of Tropical Medicine, 1996 June 14–17; Bali, Indonesia. Townsville: ACTM Publications, 1996: 27. 6. Pharmaceutical Benefits Advisory Committee, D ru g Utilization Committee.Australian statistics on medicines 1992. Canberra: Australian Government Publishing Service, 1994. 7. Pharmaceutical Benefits Advisory Committee, D ru g Utilization Committee.Australian statistics on medicines 1993. Canberra: Australian Government Publishing Service, 1995. 8. Pharmaceutical Benefits Advisory Committee, D ru g Utilization Committee.Australian statistics on medicines 1994. Canberra: Australian Government Publishing Service, 1996. 9. Pharmaceutical Benefits Advisory Committee, D ru g Utilization Committee.Australian statistics on medicines 1995. Canberra: Australian Government Publishing Service, 1997. 10. Pharmaceutical Benefits Advisory Committee, D ru g Utilization Committee. Australian statistics on medicines 1996. Canberra: Australian Government Publishing Service, 1998. 11. Pharmaceutical Benefits Advisory Committee, D ru g Utilization Committee.Australian statistics on medicines 1997. Canberra: Australian Government Publishing Service, 1999. 12. Pharmaceutical Benefits Advisory Committee, D ru g Utilization Committee.Australian statistics on medicines 1998. Canberra: Australian Government Publishing Service, 2000. 13. Williams A, Lewis DJM. Malaria prophylaxis: a postal questionnaire survey of general practitioners in South Wales. BMJ 1987; 295:1449–1452. 14. Leggat PA,Heydon JL. Trends in antimalarial drugs prescribed in New Zealand 1993 to 1998. J Travel Med 2002; 9:156–159. 15. Coole L, Wiselka MJ, Nicholson KG. Malaria prophylaxis in travellers from Britain. J Infect 1989; 18:209–212.