Liverpool COVID-19 Interactions

Potential Interaction

Nirmatrelvir/ritonavir (5 days)

Vemurafenib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Vemurafenib is metabolised by CYP3A4. Nirmatrelvir/ritonavir is metabolized by CYP3A and inhibits CYP3A. Although vemurafenib is a moderate inducer of CYP3A4, twice daily administration of ritonavir is expected to counteract the inducing effect of vemurafenib. However, vemurafenib concentrations are expected to increase due to strong inhibition of CYP3A4 by nirmatrelvir/ritonavir. Coadministration with itraconazole (a strong CYP3A4 inhibitor) increased vemurafenib AUC by 1.4-fold. A similar effect is expected with nirmatrelvir/ritonavir and coadministration is not recommended. The decision to pause or dose-adjust vemurafenib should be made in conjunction with the patient’s oncologist. If it is decided to pause vemurafenib therapy, start nirmatrelvir/ritonavir 24 hours after the last vemurafenib dose due to the long elimination half-life of vemurafenib. Restart vemurafenib 3 days after completing nirmatrelvir/ritonavir given that CYP3A4 inhibition takes several days to resolve. Alternatively, monitor for vemurafenib related toxicity if used concomitantly and interrupt therapy or consider dose reductions if necessary.

Description:

(See Summary)