Interaction between oral contraceptives and griseofulvin.

22 reports of a possible interaction between oral contraceptives (OCs) and the antifungal drug griseofulvin received by the Committee on the Safety of Medicines in the UK and the Netherlands Centre for Monitoring of Adverse Reactions to Drugs are analyzed. 15 longterm users of OCs aged 17-42 years were reported to have experienced transient intermenstrual bleeding and 5 users aged 17-44 experienced amenorrhea in the 1st or 2nd cycles after being treated with griseofulvin .5-1.0 mg daily. 2 other patients reported unintended pregnancies. 7 women with intermenstrual bleeding and with amenorrhea were using OCs containing less than 50 mcg estrogen. Patients with amenorrhea were 30.4 years old on average compared to 26.0 for those with bleeding but the difference was not statistically significant. They were also taking a higher daily dose of griseofulvin 880 mg compared to 550 mg. 14 of the 20 women had taken no other drugs 3 had used drugs not known to interfere with OCs and concomitant drug use for 3 was not known. 2 women each with intermenstrual bleeding and amenorrhea were reexposed to griseofulvin and the original reaction occurred. 1 of the women with unintended pregnancies had used a high dose OC for 15 months and had been taking griseofulvin 500 mg daily for 2 1/2 months and co-trimoxazole for 1 week during which she became pregnant. The 2nd patient had taken griseofulvin and a combination of sulphonamides at the time of conception. In the 22 patients the temporal relation between beginning griseofulvin and the occurrence of bleeding anomalies and the results of rechallenge with the drug in 4 patients are strong evidence of interaction between it and OCs. Enzyme induction and consequent lowering of estrogen concentrations may explain the intermenstrual bleeding on the basis of a withdrawal effect but amenorrhea is not as easily explained. The contributory role of griseofulvin in the 2 pregnancies is not established since both women were also taking sulphonamides.