Antimalarials
Treatment of malaria in PLWH is complicated by the risk of overlapping drug toxicities and potential drug interactions. Induction of CYP3A4 and/or CYP2C19 enzymes by artemisinin-based combination antimalarial agents is expected to potentially decrease in rilpivirine exposure . Pharmacokinetic studies of artemether have shown increase in the metabolic ratio of its active metabolite (dihydroartemisinin) over repeated doses, an effect attributed to autoinduction of CYP3A4 by artemether . Based on these observations, artemether is expected to potentially interact with rilpivirine, inducing its metabolism. The clinical significance of this potential interaction is yet to be evaluated in a clinical study. The Liverpool Drug Interactions database suggests close monitoring of cabotegravir and rilpivirine plasma concentrations and that dose adjustment may be necessary in the event of coadministration with artemisinins . Monitoring of plasma cabotegravir and rilpivirine concentrations is not readily available in most settings therefore the ability to dose-adjust will be limited.
In addition, the risk of overlapping toxicity is also a concern for concurrent use of LAI antiretroviral therapy in patients with malaria. Many antimalarial drugs have been associated with the risk of cardiac toxicity. Specifically, halofantrine, lumefantrine and quinoline derivatives (e.g. quinine, chloroquine) have been associated with delayed cardiac repolarization due to prolongation of the QT interval . Similarly, rilpivirine also prolongs the QT interval in a dose-dependent fashion. In a randomised, placebo-controlled study of 60 healthy adults, supra-therapeutic doses of rilpivirine (75mg and 300mg once daily) was shown to prolong the QTc interval, an effect not observed at the recommended dose of 25 mg orally once daily or 900 mg IM . The potential pharmacodynamic interaction between rilpivirine and antimalarial drugs predisposes to QTc interval prolongation, a risk for development of ventricular tachyarrhythmias and sudden death . Caution is advised for concurrent use of LAI rilpivirine in patients on treatment with QT-prolonging antimalarial and ECG monitoring advised.