Ranitidine versus cimetidine. A comparison of their potential to cause clinically important drug interactions.

The literature on H2-antagonist drug interactions is now extensive. The whole subject is so complicated as to make things difficult for the potential prescriber. However, it is possible to reduce most of the information contained in the literature to a few simple messages. Firstly, H2-antagonists bind to cytochrome P450 and may inhibit the metabolism of drugs eliminated by the mixed function oxygenase system. In this respect, cimetidine has a marked effect which, in most studies, has reached statistical significance. Ranitidine, on the other hand, has a much weaker effect which, even if demonstrable, is statistically non-significant. The potential benefit of ranitidine, however, has to be weighed against the relative costs of the 2 drugs. Secondly, H2-antagonists inhibit gastric acid production and may alter the rate of gastric emptying, and hence the rate of drug absorption. They may also have some effect on portal vein and hepatic artery flow. However, these effects are small and probably not clinically relevant. Thirdly, pharmacodynamic effects of H2-antagonist-drug interactions are difficult to demonstrate in planned studies, and although they are reported from time to time, adverse reactions of consequence are relatively uncommon. Fourthly, the prescriber needs to be aware that cimetidine may produce higher plasma concentrations of some drugs which have a fairly narrow therapeutic range, and this may be clinically important. Examples of drugs for which it may be undesirable to inadvertently increase plasma concentrations include warfarin, theophylline and phenytoin. Finally, for most drugs metabolised by the liver, the risk of an important interaction is small. However, if such an interaction is noted it may be helpful to refer to the other reported cases, and a number of references are included here.