Drug Interactions between Paxlovid and proguanil

GENERALLY AVOID: Coadministration with ritonavir may decrease the plasma concentrations of atovaquone and proguanil. The mechanism of interaction has not been established, but may involve ritonavir induction of the glucuronidation of atovaquone and the CYP450 2C19-mediated metabolism of proguanil. According to an open-label study from the Netherlands, HIV patients stabilized on antiretroviral regimens containing efavirenz (600 mg once daily; n=20), atazanavir/ritonavir (300 mg/100 mg once daily; n=19), or lopinavir/ritonavir (400 mg/100 mg twice daily or 800 mg/200 mg once daily; n=19) had significantly lower plasma concentrations of atovaquone and proguanil compared to healthy volunteers (n=18) following a single 250 mg/100 mg dose of atovaquone/proguanil. Specifically, atovaquone systemic exposure (AUC) was 46% lower in the atazanavir/ritonavir group and 74% lower in the lopinavir/ritonavir group than in the control group. Likewise, proguanil AUC was 41% and 38% lower in the atazanavir/ritonavir and lopinavir/ritonavir groups, respectively. The clinical significance is unknown. There are no published reports in the medical literature regarding atovaquone/proguanil treatment failure in HIV patients receiving ritonavir-boosted protease inhibitor regimens.

MANAGEMENT: The potential for treatment failure should be considered when atovaquone or atovaquone/proguanil is used with ritonavir. Some experts recommend avoiding concomitant use. If coadministration is required, an increased dosage of atovaquone and proguanil may be required.