Effect of histamine-2 receptor antagonists on blood alcohol levels: A meta-analysis

OBJECTIVE: To determine the effect, if any, of histamine type 2 receptor antagonists (H₂RAs) on serum alcohol levels under various conditions including type of H₂RA receptor antagonist, alcohol dose, and fed status of the subject. STUDY DESIGN: Meta-analysis of the published literature. DATA SOURCES: Studies were identified by MEDLINE (January 1982 through December 1997) using the key words H₂ receptor antagonists and alcohol. Other studies were identified by reviewing bibliographies of retrieved articles and by discussion with colleagues. STUDY SELECTION: Studies were selected if they involved the coadministration of H₂RAs and alcohol in healthy, human volunteers. Studies that may have addressed this goal but were performed in another context, for instance the measurement of ulcer healing. were excluded. DATA EXTRACTION: Data were extracted on the design, number of participants, participant characteristics, type and dose of H₂RA administered, serum alcohol levels (measured as C(max)) along with standard deviations, dose of alcohol received, and fed or fasted status of participants. Alcohol dose was arbitrarily divided into low dose (≤ 0.5 g/kg body weight) versus high dose (> 0.5 g/kg body weight). In addition, studies involving ranitidine and cimetidine were stratified by sample size into small (n ≤ 10) versus not small (n > 10). MEASUREMENTS AND MAIN RESULTS: Twenty- four trials met selection criteria. Small elevations in C(max) were noted when cimetidine (2.71 mg/DL; 95% confidence internal [CI] 1.60, 3.83) or ranitidine (6.95 mg/DL; 95% CI 5.83, 8.08) were coadministered with alcohol. No such differences were noted for famotidine (0.28 mg/DL; 95% CI -1.24, 1.80) or nizatidine (2.33 mg/DL;, 95% CI -0.06, 4.72). The elevation detected with cimetidine and ranitidine was most pronounced in smaller studies (n < 10). Separate analyses investigating the effect of alcohol dose and fed or fasted status of participants revealed no clinically important differences. CONCLUSIONS: Cimetidine and ranitidine, but not the other H₂RAs, can cause small elevations of serum alcohol level when alcohol and drug are administered concurrently. Studies with larger numbers of participants were less likely to demonstrate this effect. Relative to accepted, legal definitions of intoxication, the effect of any H₂RA on blood alcohol level is unlikely to be clinically relevant.