Drug interactions with oral contraceptives.

In the very rare cases where a pregnancy occurs during oral contraceptive use, the blame is usually laid against the patient for having forgotten to take the pill. Evidence has started to accumulate to suggest that neither the patient nor the pill is at fault in some contraceptive failures. It may be because the patient is taking other medicines and these may be preventing the pill from suppressing ovulation. Most drug interactions reducing or negating contraceptive activity are due to concomitant use of drugs having microsomal enzyme-inducing activity (e.g., some antibiotics, especially rifampicin, and anticonvulsants, including phenobarbital, phenytoin, and primidone. Other antibiotics (e.g., tetracycline) may also interact by interruption of the enterohepatic circulation of contraceptive steroids. Less well appreciated, oral contraceptive steroids may themselves modify the metabolism and pharmacological activity of various other drugs (e.g., anticoagulants, benzodiazepines, beta-blockers, caffeine, corticosteroids, and tricyclic antidepressants); in this respect the oral contraceptives are acting as enzyme inhibitors. Contraceptive steroids may also interact with drugs that cause enzyme inhibition and this delays the metabolism of the hormonal agents. Interactions of this type would be expected to potentiate the action of the contraceptive steroids. It is suggested that the effects of such interaction might be presented in terms of increased incidence of side effects, including water retention, diabetogenic effects, hypertension, and an increased risk of thromboembolic disorders. The spectrum of interactions with oral contraceptives is presented in three tables.