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Zelboraf (Vemurafenib) - Drug Interactions, Contraindications, Overdosage, etc



Effects of Vemurafenib on Drug Metabolizing Enzymes

Results from an in vivo drug-drug interaction study in patients with cancer demonstrated that vemurafenib is a moderate CYP1A2 inhibitor, a weak CYP2D6 inhibitor and a CYP3A4 inducer [see Clinical Pharmacology].

Coadministration of vemurafenib increased the AUC of caffeine (CYP1A2 substrate) 2.6-fold and increased the AUC of dextromethorphan (CYP2D6 substrate) by 47%, while it decreased the AUC of midazolam (CYP3A4 substrate) by 39% [see Clinical Pharmacology]. Concomitant use of ZELBORAF with agents with narrow therapeutic windows that are metabolized by CYP1A2, CYP2D6 and CYP3A4 is not recommended as ZELBORAF may alter their concentrations. If coadministration cannot be avoided, exercise caution and consider a dose reduction of the concomitant CYP1A2 and CYP2D6 substrate drug.

Coadministration of vemurafenib resulted in an 18% increase in AUC of S-warfarin (CYP2C9 substrate) [see Clinical Pharmacology]. Exercise caution and consider additional INR monitoring when ZELBORAF is used concomitantly with warfarin.

Drugs that Inhibit or Induce CYP3A4

Based on in vitro data, vemurafenib is a substrate of CYP3A4, and therefore, concomitant administration of strong CYP3A4 inhibitors or inducers may alter vemurafenib concentrations. Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) and inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) should be used with caution when coadministered with ZELBORAF.


There is no specific antidote for overdosage of ZELBORAF. Patients who develop adverse reactions should receive appropriate symptomatic treatment. In case of suspected overdose, ZELBORAF should be withheld and supportive care instituted.




No studies on the potential for ZELBORAF to cause dependence have been performed. However, there is no evidence from the available data that ZELBORAF treatment can result in dependence.

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