Drug Interactions between Acid Reducer-Cimetidine and zaleplon

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zaleplon. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of zaleplon with a high-fat or heavy meal may delay the onset of hypnotic effects. In healthy adult subjects, administration of zaleplon with a high-fat meal resulted in a 2-hour delay in the time to reach peak plasma drug concentration (Tmax) and a 35% reduction in the peak plasma drug concentration (Cmax) compared to fasting. Zaleplon systemic exposure (AUC) and elimination half-life were not significantly affected.

MANAGEMENT: Patients receiving zaleplon should be advised to avoid the consumption of alcohol. For faster sleep onset, zaleplon should not be administered with or immediately after a high-fat or heavy meal.

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.