Mefloquine Ritonavir

In studies of combining ritonavir with fluconazole (2) and ritonavir with mefloquine (3) there were no significant effects, and dosage adjustment is not warranted. 

Khaliq Y, Gallicano K, Tisdale C, Carignan G, Cooper C, McCarthy A. Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers. Br J Clin Pharmacol 2001 51(6) 591-600. 

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. 

Data from individual patients surest there is no pharmacokinetic interaction between mefloquine and indinavir or nelfinavir. In pharmacokinetic studies in healthy subjects, ritonavir did not alter mefloquine pharmacokinetics, but mefloquine modestly decreased steady-state ritonavir levels. 

In 12 healthy subjects ritonavir 200 mg twice daily for one week had no significant effect on the pharmacokinetics of mefloquine. Conversely, mefloquine (250 mg once daily for 3 days, then 250 mg weekly) significantly reduced the steady-state AUC, and maximum and minimum plasma levels of ritonavir 200 mg twice daily, by 31%, 36%, and 43%, respectively, but had no effect on the pharmacokinetics of single-dose ritonavir. ... 

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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