Drug Interaction Report

The solubility of vismodegib is known to be pH-dependent (0.1 mcg/mL at pH 7 and 0.99 mg/mL at pH 1) and drugs that alter the pH of the upper gastrointestinal tract may affects its solubility and reduce its bioavailability. However, a clinically significant pharmacokinetic effect has not been observed, with results from a clinical study showing a 33% reduction in the unbound drug concentrations of vismodegib after 7 days of concomitant therapy with the proton pump inhibitor rabeprazole (20 mg, given 2 hours before each vismodegib administration).

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.