Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?
BACKGROUND
Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing.


METHODS
We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine.


CONCLUSIONS
We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks.


METHODS
Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.
Croft
Ashley M
AM
Surgeon General's Department, Ministry of Defence, St Giles' Court, London WC2H 8LD, UK. AshleyCroft@compuserve.com
Herxheimer
Andrew
A
D000208:Acute Disease; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004347:Drug Interactions; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008107:Liver Diseases / Q000150:complications*; D008288:Malaria / Q000150:complications / Q000188:drug therapy*; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects*; D012449:Safety; D013959:Thyroid Diseases / Q000150:complications*
D000962:Antimalarials; D015767:Mefloquine