Drug interactions of Vemurafenib

1. Effect of Strong CYP3A4 Inhibitors or Inducers on Vemurafenib

Strong CYP3A4 Inhibitors

Coadministration of a strong CYP3A4 inhibitor increased vemurafenib plasma concentrations and may lead  to increased toxicity. Avoid coadministration of Vemurafenib with strong CYP3A4 inhibitors. If  coadministration of a strong CYP3A4 inhibitor is unavoidable, consider dose reduction of Vemurafenib, if clinically indicated.  

Strong CYP3A4 Inducers

Coadministration of Vemurafenib with rifampin, a strong CYP3A4 inducer, decreased vemurafenib plasma concentrations and may result in decreased efficacy. Avoid coadministration of Vemurafenib with strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin), and replace these drugs with alternative drugs  when possible. If coadministration of a strong CYP3A4 inducer is unavoidable, increase the dose of  Vemurafenib by 240 mg (one tablet) as tolerated.  

2. Effect of Vemurafenib on CYP1A2 Substrates

Coadministration of Vemurafenib with tizanidine, a sensitive CYP1A2 substrate, increased tizanidine systemic exposure by 4.7-fold. Avoid concomitant use of Vemurafenib with drugs having a narrow therapeutic window that are predominantly metabolized by CYP1A2. If  coadministration cannot be avoided, monitor closely for toxicities and consider a dose reduction of  concomitant CYP1A2 substrates.

3. Concurrent Ipilimumab

Increases in transaminases and bilirubin occurred in a majority of patients who received concurrent  ipilimumab and Vemurafenib.

4. Effect of Vemurafenib on P-gp Substrates

Coadministration of Vemurafenib with digoxin, a sensitive P-glycoprotein (P-gp) substrate, increased digoxin systemic exposure by 1.8-fold. Avoid concurrent use of P-gp substrates known to have narrow therapeutic indices. If use of these medications is unavoidable, consider dose reduction of P-gp substrates  with narrow therapeutic indices.

from FDA，2020.12