Histamine H2-antagonist drug interactions in perspective: mechanistic concepts and clinical implications

Histamine H2-antagonists have the ability to produce fundamental changes in the absorption and disposition of other drugs. However, there are similarities and differences between the H2-antagonists in this respect, depending on the process involved. By increasing the intragastric pH any H2-antagonist has the potential of altering the absorption of weak acids or weak bases. However, since the rise in intragastric pH is not immediate, as with antacids, this type of interaction might be avoided for concomitantly administered, rapidly absorbed drugs. Whereas cimetidine inhibits hepatic mixed-function oxidase drug metabolism, ranitidine does not have this characteristic. Clinical studies have found that cimetidine produces a 20 to 60 percent decrease in the clearance of 23 drugs (such as warfarin, theophylline, quinidine, phenytoin, imipramine, propranolol, nifedipine). Marketed and investigational H2-antagonist drugs differ in their ability to inhibit drug metabolism due to the combined characteristics of cytochrome P-450 binding affinity and therapeutic dosage. Cimetidine also inhibits the renal-tubular secretion of other weak bases (such as procainamide). Management suggestions are presented to help clinicans predict and avoid failure in drug therapy as a result of these drug interactions.