Mefloquine Protease inhibitors

Anti-infective drugs Ciprofloxacin can greatly increase the risk of seizure induction in patients taking anticonvulsants. Erythromycin produces a rapid 100-200% rise in carbamazepine levels. There is a possibility of reduced plasma levels of the protease inhibitors indinavir and saquinavir with carbamazepine. Isoniazid increases carbamazepine serum levels, and leads to the possible emergence of toxicity (disorientation and aggression). Mefloquine may antagonize the anticonvulsant effect of carbamazepine. Ritonavir, a protease inhibitor, may cause toxicity by raising carbamazepine plasma levels. 

Two HIV-positive patients using HAART, one taking indinavir 800 mg three times daily, the other taking nelfinavir 1.25 g twice daily were given mefloquine 250 mg weekly, before a trip to Africa. Mefloquine achieved therapeutic levels, and its half-life was similar to that found in healthy subjects. In addition, no consistent changes in the plasma levels of the protease inhibitors were found. ... 

Despite being inhibitors of the cytochrome P450 isoenzyme CYP3A4, the protease inhibitors do not appear to alter mefloquine pharmacokinetics. It was suggested that the decrease in ritonavir levels was due to decreased absorption, perhaps due to mefloquine-induced inhibition of bile acid production or induction of P-glycoprotein. ... 

The limited evidence suggests that protease inhibitors do not affect mefloquine pharmacokinetics. The data on the effect of mefloquine on ritonavir are less clear. Until further evidence is available, it may be prudent to closely monitor ritonavir levels/efficacy if mefloquine is required. 

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