Clinically important adverse effects and drug interactions with H2-receptor antagonists: an update

The H2-receptor antagonists cimetidine, ranitidine, and famotidine are well tolerated, with a low frequency and similar spectrum of adverse effects. The occasional problematic effects that have been associated with these agents include central nervous system symptoms (mental confusion, headache, and depression), rare cases of thrombocytopenia, and cardiovascular events related to the rate of intravenous infusion. Severe renal and hepatic impairment appear to be associated with a higher occurrence of central nervous system effects. Because the H2-receptor antagonists elevate gastric pH, bind to and inhibit the hepatic cytochrome P-450 enzyme system, and undergo renal tubular secretion, competition with other drugs sharing these pathways has resulted in a number of drug interactions, most of which are not clinically significant. The interaction that occurs with theophylline and warfarin when the cytochrome P-450 enzyme system is inhibited by cimetidine and ranitidine requires monitoring. Recent data suggest that administering cimetidine 800 mg at bedtime has less effect on the serum concentrations of warfarin and theophylline than other dosing regimens. Evidence to date indicates that famotidine does not bind to cytochrome P-450 to a significant extent, and interactions with drugs metabolized by this system have not been reported; however, clinical experience with this agent is very limited.