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.