Drug Interactions between AccessPak for HIV PEP Expanded with Viracept and sotorasib

MONITOR: Coadministration with drugs that are inducers of CYP450 3A4 may decrease the plasma concentrations of protease inhibitors (PIs), which are primarily metabolized by the isoenzyme.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, protease inhibitors should be used cautiously with agents that induce CYP450 3A4, particularly if only one PI is used in the antiretroviral regimen. Coadministration of atazanavir without ritonavir and carbamazepine, phenobarbital, or phenytoin is not recommended. Antiretroviral response should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the antiretroviral regimen adjusted as necessary.

MONITOR: Coadministration with sotorasib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) membrane transporters. The proposed mechanism involves enhanced absorption and bioavailability of substrate drugs due to inhibition of intestinal P-gp- and BCRP-mediated efflux by sotorasib. Inhibition of P-gp and BCRP transport in other organs such as the liver and kidney may also contribute in some cases, especially for non-oral drugs. When digoxin, a sensitive P-gp substrate, was coadministered with sotorasib, digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 91% and 21%, respectively. When rosuvastatin, a BCRP substrate, was coadministered with sotorasib, rosuvastatin Cmax and AUC increased by 70% and 34%, respectively.

MANAGEMENT: Caution is advised when sotorasib is used concurrently with drugs that are P-gp and/or BCRP substrates, particularly those with a narrow therapeutic range. The prescribing information recommends avoiding coadministration of sotorasib with P-gp and BCRP substrates for which minimal concentration changes may lead to serious toxicities. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever sotorasib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a P-gp and BCRP inhibitor like sotorasib and for any dosage adjustments that may be required.