Abstract
Malaria is still one of the most important tropical diseases, killing millions every year. The number of effective drugs is limited, because of the ability of the causative parasite Plasmodium falciparum to develop drug resistance. Mefloquine, if possible in combination with an artemisinin derivative, is the only efficacious treatment left for uncomplicated but highly multidrug-resistant P. falciparum infections encountered in some areas. Mefloquine remains effective in most endemic areas worldwide for both prophylaxis and treatment of malaria.
Generally, mefloquine is well tolerated but it is associated occasionally with neuropsychiatric adverse effects, whether used as treatment or for prophylaxis. In recent years, mefloquine has acquired a bad reputation mainly because of reports of neuropsychiatric reactions in travellers. These reports were widely publicised and amplified by the media. As a result, the confusion about recommendations for the prophylaxis of malaria has deepened and decisions on prophylactic regimens have been made that could have serious consequences. However, there is little evidence that the use of mefloquine should be avoided because of the risk of these adverse effects.
Although studies have shown that mefloquine is associated with neuropsychiatric adverse effects, most of these events have been mild and self-limiting. Some predisposing factors to the occurrence of neuropsychiatric adverse effects, such as a family history or a past history of neuropsychiatric disorders, recent (last 2 months) previous exposure to mefloquine or use of psychotropic drugs, were identified. Use of mefloquine should not be considered in these cases. Updated information about contraindications to mefloquine and the risk of malaria in areas visited should be available for medical professionals and patients.
All antimalarials have adverse effects; it is therefore essential to balance the risks and the benefits each time a malaria prophylaxis regimen is prescribed.
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References
Nosten F, van Vugt M. Malaria, still no vaccine and very few drugs. Curr Opin Infect Dis 1996; 9: 429–34
Paris L, Caumes E, Bustos M, et al. Resistance of Plasmodium falciparum to mefloquine in Sierra Leone and Kenya [letter]. Presse Med 1990; 19(27): 1283
Nosten F, Luxemburger C, ter Kuile F, et al. Treatment of multi-drug-resistant Plasmodium falciparum malaria with 3- day artesunate-mefloquine combination. J Infect Dis 1994; 170 (4): 971–7
White NX Mefloquine [editorial]. BMJ 1994; 308(6924): 286–7
Palmer KJ, Holliday SM, Brogden RN. Mefloquine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1993; 45(3): 430–75
Lobel HO, Keystone JS. Confusion on malaria chemoprophylaxis [letter]. Lancet 1994; 343(8890): 183
Cook GC. Malaria prophylaxis. Mefloquine toxicity should limit its use to treatment alone [letter]. BMJ 1995; 311(6998): 190–1
CIOMS International reporting of adverse drug reactions. CIOMS Working Group Report. Geneva: World Health Organization, 1997
World Health Organization. Review of central nervous system adverse events related to the antimalarial drug mefloquine (1985–1990). WHO/MAL/91.1063. Geneva: World Health Organization, 1991
Lobel HO, Miani M, Eng T, et al. Long-term malaria prophylaxis with weekly mefloquine. Lancet 1993; 341(8849): 848–51
Hoebe C, de MJ, Thijs C. Side effects and compliance with mefloquine or proguanil antimalarial chemoprophylaxis. Eur J Clin Pharmacol 1997; 52(4): 269–75
Steffen R, Fuchs E, Schildknecht J, et al. Mefloquine compared with other malaria chemoprophylactic regimens in tourists visiting east Africa. Lancet 1993; 341(8856): 1299–303
Barrett PJ, Emmins PD, Clarke PD, et al. Comparison of adverse events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travelers. BMJ 1996; 313(7056): 525–8
Carme B, Peguet C, Nevez G. Compliance with and tolerance of mefloquine and chloroquine + proguanil malaria chemoprophylaxis in French short-term travellers to sub-Saharan Africa. Trop Med Int Health 1997; 2(10): 953–6
Sanchez JL, DeFraites RF, Sharp TW, et al. Mefloquine or doxycycline prophylaxis in US troops in Somalia [letter]. Lancet 1993; 341(8851): 1021–2
Davis TM, Dembo LG, Kaye-Eddie SA, et al. Neurological, cardiovascular and metabolic effects of mefloquine in healthy volunteers: a double-blind, placebo-controlled trial. Br J Clin Pharmacol 1996; 42(4): 415–21
Riemsdijk van RM, van der Klauw MM, van HJ, et al. Neuropsychiatric effects of antimalarials. Eur J Clin Pharmacol 1997; 52(1): 1–6
Croft AM, Clayton TC, World MJ. Side effects of mefloquine prophylaxis for malaria: an independent randomized controlled trial. Trans R Soc Trop Med Hyg 1997; 91(2): 199–203
Arthur JD, Shanks GD, Echeverria P. Mefloquine prophylaxis [letter]. Lancet 1990; 335(8695): 972
Schlagenhauf P, Steffen R, Lobel H, et al. Mefloquine tolerability during chemoprophylaxis: focus on adverse event assessments, stereochemistry and compliance. Trop Med Int Health 1996; 1(4): 485–94
Nosten F, Karbwang J, White NJ, et al. Mefloquine antimalarial prophylaxis in pregnancy: dose finding and pharmacokinetic study. Br J Clin Pharmacol 1990; 30(1): 79–85
Bunnag D, Malikul S, Chittamas S, et al. Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial. Southeast Asian J Trop Med Public Health 1992; 23 (4): 777–82
Ohrt C, Richie TL, Widjaja H, et al. Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1997; 126(12): 963–72
Salako LA, Adio RA, Walker O, et al. Mefloquine-sulphadoxine-pyrimethamine (Fansimef, Roche) in the prophylaxis of Plasmodium falciparum malaria: a double-blind, comparative, placebo-controlled study. Ann Trop Med Parasitol 1992; 86(6): 575–81
Bern JL, Kerr L, Stuerchler D. Mefloquine prophylaxis: an overview of spontaneous reports of severe psychiatric reactions and convulsions. J Trop Med Hyg 1992; 95(3): 167–79
Boudreau E, Schuster B, Sanchez J, et al. Tolerability of prophylactic Lariam regimens. Trop Med Parasitol 1993; 44(3): 257–65
Sturchler D, Handschin J, Kaiser D, et al. Neuropsychiatric side effects of mefloquine [letter]. N Engl J Med 1990; 322(24): 1752–3
Le NN, De VP, Le TD, et al. Single dose artemisinin-mefloquine versus mefloquine alone for uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 1997; 91(2): 191–4
Croft A, Garner P. Mefloquine to prevent malaria: a systematic review of trials. BMJ 1997; 315(7120): 1412–6
Behrens RH, Erny S, Maradit H, et al. Mefloquine to prevent malaria [letters]. BMJ 1998; 7149: 1980–1
Hopperus Buma APCC, van Thiel PPAM, Lobel HO, et al. Long-term malaria chemoprophylaxis with mefloquine in Dutch marines in Cambodia. J Infect Dis 1996; 173: 1506–9
Phillips-Howard PA, ter Kuile F. CNS adverse events associated with antimalarial agents: fact or fiction? Drug Saf 1995; 12(6): 370–83
Vuurman EF, Muntjewerff ND, Uiterwijk MM, et al. Effects of mefloquine alone and with alcohol on psychomotor and driving performance. Eur J Clin Pharmacol 1996; 50(6): 475–82
Wittes RC, Saginur R. Adverse reaction to mefloquine associated with ethanol ingestion. Can Med Assoc J 1995; 152(4): 515–7
Winstanley P. Mefloquine: the benefits outweigh the risks. Br J Clin Pharmacol 1996; 42(4): 411–3
Sowunmi A, Salako LA, Oduola AM, et al. Neuropsychiatric side effects of mefloquine in Africans. Trans R Soc Trop Med Hyg 1993; 87(4): 462–3
Luxemburger C, Nosten F, ter Kuile F, et al. Mefloquine for multidrug-resistant malaria [letter]. Lancet 1991; 338: 1268
ter Kuile F. Mefloquine, halofantrine and artesunate in the treatment of uncomplicated falciparum malaria in a multidrug resistant area [PhD thesis]. Amsterdam: University of Amsterdam, 1994
Nguyen TH, Day NP, Ly VC, et al. Post-malaria neurological syndrome. Lancet 1996; 348(9032): 917–21
Luxemburger C, Price RN, Nosten F, et al. Mefloquine in infants and young children. Ann Trop Paediatr 1996; 16(4): 281–6
McGready R, Cho T, Hkirijaroen L, et al. Quinine and mefloquine in the treatment of multidrug-resistant Plasmodium falciparum in pregnancy. Ann Trop Med Parasit 1998; 92(6): 643–53
Looareesuwan S, Wilairatana P, Molunto W, et al. A comparative clinical trial of sequential treatments of severe malaria with artesunate suppository followed by mefloquine in Thailand. Am J Trop Med Hyg 1997; 57(3): 348–53
Jones R, Kunsman G, Levine B, et al. Mefloquine distribution in postmortem cases. Forensic Sci Int 1994; 68(1): 29–32
Pham YT, Nosten F, Farinotti R, et al. Cerebral uptake of mefloquine enantiomers in fatal cerebral malaria. Int J Clin Pharmacol. In press
Speich R, Haller A. Central anticholinergic syndrome with the antimalarial drug mefloquine [letter]. N Engl J Med 1994; 331 (1): 57–8
Petersen E, Hogh B, Bygbjerg IC, et al. Malaria chemoprophylaxis: why mefloquine? [letter]. Lancet 1990; 336(8718): 811
Behrens RH, Bradley DJ, Snow RW, et al. Impact of UK malaria prophylaxis policy on imported malaria [letter]. Lancet 1996; 348(9023): 344–5
CDR Review-Communicable Disease Report 1997; 10: 137-152
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Nosten, F., van Vugt, M. Neuropsychiatric Adverse Effects of Mefloquine. Mol Diag Ther 11, 1–8 (1999). https://doi.org/10.2165/00023210-199911010-00001
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DOI: https://doi.org/10.2165/00023210-199911010-00001