Drug Interaction Report

MONITOR: Ranitidine may increase the active metabolites and effects of morphine. Diamorphine is a prodrug of morphine and, according to its manufacturer, the mechanism of this interaction may involve inhibition of morphine glucuronidation by ranitidine. Morphine is metabolized to morphine-3-glucuronide (M3G) which has no opioid activity, and morphine-6-glucuronide (M6G), which is a potent opioid receptor agonist. In a double-blind cross-over study on 8 volunteers, oral morphine was administered with ranitidine or placebo. Compared to placebo, ranitidine significantly reduced the individual serum M3G/M6G ratio and tended to increase the systemic exposure (AUC) of morphine. In contrast, ranitidine had no significant effect on the urinary M3G/M6G ratio.

MANAGEMENT: Caution is advised when diamorphine or morphine are used with ranitidine. Patients should be monitored for increased opioid effects. A dose reduction of the opioid may be considered if an interaction is suspected.

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.