Drug interaction with oral contraceptive steroids.

A number of major studies in the past 4 years have facilitated assessment of drug interactions with the steroids in oral contraceptive (OCs). In 8 women receiving a single dose of Minovlar during rifampicin therapy and another dose 1 month after stopping rifampicin, rifampicin reduced the half-life of norethisterone from 6.2 to 3.2 hours, the half-life of ethinyl estradiol (EE) from 6.5 to 2.9 hours, and considerably reduced the bioavailability of both. All patients showed evidence of microsomal enzyme induction. Because of the wide variation in response, women using rifampicin should not use OCs, especially low-dose OCs. A recent study described the effects of the anticonvulsant phenobarbitone (30 mg twice daily) on 4 women taking OCs who were studied 1 month before and 2 months after phenobarbitone was started. 2 women with significant falls in plasma EE concentration developed breakthrough bleeding while the other 2 showed no change in EE or norgestrel. Sex-hormone-blinding globulin capacity increased by 28% during therapy, reducing the free concentration of progestagen in plasma. Most practitioners advise the use of other contraceptive methods with anticonvulsants. Although there is no doubt that in experimental animals antibiotics interfere with the enterohepatic circulation of synthetic steroids, clinical studies have failed to show any systematic interaction between ampicillin and OC steroids in humans, and more recent studies have failed to show interaction between either erythromycin or tetracycline and OCs in women with acne vulgaris or cotrimoxazole and OCs in normal volunteers. Further data are needed before clear advice can be given to women. Ascorbic acid has recently been found to enhance the effect of OCs: the plasma concentration of EE is significantly higher in OC users taking 1 g of ascorbic acid than in the same subjects taking the OC alone.