Drug Interaction Report

Coadministration with CYP450 3A4 inhibitors is not expected to have clinically significant effects on the plasma concentrations of cabazitaxel, a narrow therapeutic index drug, which is primarily metabolized via the isoenzyme. A drug interaction study in patients with advanced cancers (n=13), revealed repeated administration of the moderate CYP450 3A4 inhibitor aprepitant (125 mg or 80 mg once daily) did not modify the exposure to cabazitaxel (15 mg/m2 intravenous). Clinical data with less potent CYP450 3A4 inhibitors are not available.

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

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.