Drug Interaction Report

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 CYP450 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vemurafenib is added to or withdrawn from therapy.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.

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.