Minocycline Topical and Gestodene: Interaction Details

a) In a multicenter study, hormone levels over 1 menstrual cycle were evaluated in women administered low-dose contraceptives concomitantly with minocycline hydrochloride extended-release formulation (1 mg/kg once daily) and in those who received low-dose contraceptives alone. Minocycline-related changes in plasma levels of estradiol, progestinic hormone, follicle stimulating hormone, and luteinizing hormone, as well as breakthrough bleeding and contraceptive failure cannot be ruled out based on the results of this study. Therefore, women are advised to use an additional form of birth control during concomitant treatment with minocycline ¹.

b) There was no significant difference in oral contraceptive (OC) failure rates among women who received OC with or without concomitant antibiotics, including tetracyclines; and the OC failure rate in both groups did not exceed a typical contraceptive failure rate of 1% to 3% in a retrospective chart review and follow-up survey. Of 356 women who received antibiotics and OC concurrently over 311.2 woman-years, 5 pregnancies occurred yielding a rate of 1.6 pregnancies per 100 woman-years or a 1.6%/year failure rate. Of 425 control patients who received OC without antibiotics for 1244.9 woman-years, 12 pregnancies occurred yielding a rate of 0.96 pregnancies per 100 woman-years or 0.96%/year failure rate. The difference in failure rate between these groups was not significant (95% CI on the difference, -0.81 to 2.1; p=0.4) and ruled out a substantial difference (greater than 2.1% per year). The women in the control group consisted of 263 women who received OC but did not concomitantly use OC with antibiotics and 162 OC users who never concomitantly used antibiotics. Among women who never concomitantly used antibiotics (n=162) over 551.2 woman-years, 7 pregnancies occurred, yielding a rate of 1.3 pregnancies per 100 woman-years or 1.3%/year failure rate ³.

c) There was no increased risk of contraceptive failure with concomitant antibiotic use in a study of 34 patients with acne who used oral antibiotics, including tetracycline (n=17) and erythromycin (n=20), concomitantly with low estrogen oral contraceptives for a total period of 71 women-years.. The calculated contraceptive failure rate was 1.4 per 100 women-years for the study, which was not significantly different than an accepted and documented contraceptive failure rate of 0.27 per 100 women-years (p=0.17). Of the 34 patients, one became pregnant while using the norethindrone, ethinyl estradiol, and mestranol combination concomitantly with oral tetracycline (12 months duration of use). The patient stated that she did not miss any doses of the contraceptive combination or had any changes in her menstrual cycle. Two other patients reported menstrual irregularities; one reported spotting while using the ethinyl estradiol and ethynodiol diacetate combination concomitantly with terfenadine and minocycline treatment, and another reported heavy cramping while using the norethindrone acetate and ethinyl estradiol combination concomitantly with tetracycline. Although this study determined that there was no increased risk of contraceptive failure with concomitant antibiotic use, the data suggests that tetracycline and its derivatives may interact with low-dose estrogen contraceptives ².

d) In a retrospective cohort study using chart reviews and surveys, the oral contraceptive failure rate for combined use with oral antibiotics was 1.6 pregnancies per 100 woman-years of exposure, compared with a failure rate of 0.96 in the control group. Five pregnancies resulted in the antibiotic-exposed group, and all of these women had been using oral contraceptives for at least 6 months at the time of pregnancy and had been taking antibiotics for at least 3 months. Three of the five pregnancies occurred in women taking minocycline, while the other two pregnancies occurred in women receiving a cephalosporin ⁴.

e) The interaction between oral contraceptives and tetracycline has been suggested to be due to an alteration of the gut flora. The normal gut flora is thought to be responsible for the hydrolysis of the glucuronide moiety (estrogen metabolite found in the bile) to free drug. When the gut flora is altered, enterohepatic recirculation is reduced and the metabolite is simply excreted. This causes a decrease in body levels of the estrogen and reduced effectiveness ⁵.

f) During a four-year period documenting 163 cases of contraceptive failure in reliable pill takers, 37 cases of pill failures (23%) were attributed to the concomitant use of antibiotics. Tetracyclines, including minocycline, were featured in 6 of these 37 cases ⁶.