Vemurafenib and Caffeine

Vemurafenib may increase the blood levels and effects of caffeine. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR: Coadministration with vemurafenib may increase the plasma concentrations of drugs that are substrates of the CYP450 1A2 and/or 2D6 isoenzymes. The mechanism is decreased clearance due to inhibition of CYP450 1A2 and 2D6 activity by vemurafenib. The interaction has been studied with caffeine and dextromethorphan, probe substrates for CYP450 1A2 and 2D6, respectively. In an in vivo phenotypic cocktail drug-drug interaction study in patients with cancer, caffeine systemic exposure (AUC) increased by 2.6-fold when a single dose of the CYP probe substrate cocktail was administered following treatment with vemurafenib 960 mg twice daily for 15 days, while dextromethorphan AUC increased by 47%.

MANAGEMENT: Caution is advised if vemurafenib must be used concurrently with drugs that undergo metabolism by CYP450 1A2 and/or 2D6. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vemurafenib is added to or withdrawn from therapy. Concomitant use of vemurafenib and substrates of CYP450 1A2 and/or 2D6 with a narrow therapeutic index (e.g., antiarrhythmics; theophylline) should be avoided if possible.