Mefloquine safety and tolerability in pregnancy: a systematic literature review

Abstract

Background: Control of malaria in pregnant women is still a major challenge as it constitutes an important cause of maternal and neonatal mortality. Mefloquine (MQ) has been used for malaria chemoprophylaxis in non-immune travellers for several decades and it constitutes a potential candidate for intermittent preventive treatment in pregnant women (IPTp). Methods: The safety of MQ, including its safety in pregnancy, is controversial and a continuing subject of debate. Published studies which evaluated the use of MQ for malaria prevention or treatment in pregnant women and which reported data on drug tolerability and/or pregnancy outcomes have been reviewed systematically.

Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial

“…In the present study, MQ tolerability appeared to improve with each subsequent dose of MQ. The reduced frequency of reported AEs with repeated number of administrations has been observed in other studies of MQ among pregnant women but also in non-pregnant women travelling in malaria endemic regions [21],[49]–[51]. This study confirmed the safety of MQ with regard to stillbirths, which has also been observed among HIV-negative women [21],[25].…”

Animal Embryotoxicity Studies of Key Non‐Artemisinin Antimalarials and Use in Women in the First Trimester

“…Among the articles that met the inclusion criteria for a February, 2014, review (Gonzalez et al, ) were the six articles discussed in the preceding paragraphs and seven articles that found no adverse effects of mefloquine treatment during pregnancy on the rates of abortions, stillbirths, and/or congenital anomalies. In the five of these seven negative studies in which mefloquine was used for the treatment of malaria, there was a total of 7 pregnant women exposed during the first trimester (∼10 mg/kg twice, 6 hr apart; Harinasuta et al, ), 309 pregnant women exposed to mefloquine alone during the second and third trimesters (Harinasuta et al, ; McGready et al, ; Adam et al, ), and 88 exposed during the second and third trimesters to the combination of mefloquine with artemether (Sowunmi et al, ) or artesunate (McGready et al, ).…”

Comparative study of mefloquine and sulphadoxine–pyrimethamine for malaria prevention among pregnant women with HIV in southwest Nigeria

“…Both the US Centers for Disease Control and Prevention and the French Reference Center on Teratogenic Agents consider mefloquine appropriate for chemoprophylaxis for women at all pregnancy durations travelling to high‐risk areas. Mefloquine has also been classified as pregnancy category B by the US Food and Drug Administration . Although WHO does not recommend the use of mefloquine for IPTp at a dose of 15 mg/kg owing to the high incidence (30%) of adverse effects such as vomiting and dizziness, they have suggested further studies at lower doses.…”

“…Although WHO does not recommend the use of mefloquine for IPTp at a dose of 15 mg/kg owing to the high incidence (30%) of adverse effects such as vomiting and dizziness, they have suggested further studies at lower doses. In addition, mefloquine is contraindicated for individuals with background neuropsychiatric illness including epilepsy . A lower dose of 250 mg was used for prophylaxis in earlier studies .…”