PIP: Oral contraceptives (OCs) should be used with additional caution in combination with other drugs in certain disease states. This discussion focuses on only those interactions which are due to identifiable pharmacokinetic processes. Pharmacological interactions between OCs and other compounds may be of 2 kinds: drugs may impair the effectiveness of the OCs to cause breakthrough bleeding or to allow pregnancy to occur; and OCs may interfere with the metabolism of other componds. In general, interactions of the 1st kind are due to interference with the absorption, metabolism, or excretion of estrogens, and interactions of the 2nd kind are due to competition for metabolic pathways. It is difficult to obtain estimates of the frequency of interactions, but it seems likely that, as low-dose preparations become more widely used, interactions of the 1st type will become more common and those of the 2nd type less common. Although it is probably only those women with low plasma hormone concentrations who are at risk that other drugs may interfere with contraceptive efficacy, and women with high plasma concentrations of estrogen who are at risk of side-effects and that OCs may interfere with other drugs, there is no way of detecting women in either category. Consequently, it is safer for the present to assuume that all women who take OCs might be at risk of some form of interaction. Significant drug interactions in which contraceptive efficacy is reduced are more likely to occur in the early part of the cycle when circulating hormone concentrations are of critical importance. It is well known that infective diarrhea can induce OC failure by increasing gastrointestinal motility and reducing hormone absorption. Thus, any drug which reduces gut transit time and causes diarrhea is potentially likely to reduce circulating concentrations of OCs. The sulphation of ethinl-estradiol in the gastrointestinal wall has been shown to be a site of interaction for the enhancement of the activity of OCs. Ascorbic acid also undergoes sulphate conjugation in the gut wall and acts as a competitive inhibitor for sulphation of estrogens. The most clinically significant group of interactions occurs with other drugs that are metabolized by the same hepatic microsomal pathways as is estrogen. Most of the anticonvulsant drugs are inducers of microsomal enzymes. Rifampicin is known to be a potent inducer of hepatic microsomal enzymes and has been shown to increase the rate of metabolism of both estrogeens and progestogens. A recent report has suggested that the antifugal drug griseofulvin may cause a clinically important interaction with OCs. There are numerous well documented clinical reports of women who have taken OCs without missing a dose who have become pregnant while taking a variety of antibiotic agents such as ampicllin and tetracycline. Estrogens are inhibitors of hepatic microsomal enzymes. In this way they may show the metabolsim of other drugs, thus increasing their plasma and tissue concentrations and increasing the risk of side-effects. These interactions might be expected to become less common as the concentration of estrogen in OCS decreases.