Liverpool COVID-19 Interactions

Potential Interaction

Nirmatrelvir/ritonavir (5 days)

Etoposide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Etoposide is partly metabolized by CYP3A4 and partly glucuronidated by UGT1A1 to reactive catechol metabolites. Conversion to reactive metabolites can also be mediated by prostaglandin synthase or myeloperoxidase. In vitro data suggest etoposide may also be a P-gp substrate. Nirmatrelvir/ritonavir is a strong inhibitor of CYP3A4 and P-gp and is expected to increase etoposide concentrations. Coadministration with ketoconazole, a strong CYP3A4 inhibitor, increased etoposide exposure by 20%. A similar effect is expected with nirmatrelvir/ritonavir and therefore can increase the risk of adverse effects. The decision to pause or dose adjust etoposide should be made in conjunction with the patient’s oncologist. If it is decided to pause etoposide treatment, restart etoposide 3 days after completing nirmatrelvir/ritonavir treatment given that CYP3A4 inhibition by ritonavir takes several days to resolve. Alternatively, if coadministration is necessary monitor closely for etoposide toxicity and consider a dose reduction. Resume previous dose 3 days after completing nirmatrelvir/ritonavir treatment. Although ritonavir may induce glucuronidation, given that induction reaches maximal effect after several days and the short duration of nirmatrelvir/ritonavir treatment, no effect on etoposide due to UGT induction is anticipated.

Description:

(See Summary)