The Impact of Antibiotics on Contraceptive Regimens

by Pelin Batur, MD

A 27-year-old woman presents with a dog bite on her right hand and is started on oral antibiotics. She takes an oral contraceptive that contains 35 μg of ethinyl estradiol and 0.25 mg of norgestimate. She asks if she should use condoms while taking antibiotics.

The antibiotics rifampin and rifabutin are known inducers of the hepatic enzymes required for contraceptive steroid metabolism, whereas other antibiotics are not. Despite the lack of compelling evidence that broad-spectrum antibiotics interfere with the efficacy of hormonal contraception, most pharmacists recommend backup contraception for women who use concomitant antibiotics.1 This practice could lead to poor compliance with the contraceptive regimen, the antibiotic regimen, or both.1

Simmons et al1 conducted a systematic review of randomized and nonrandomized studies that assessed pregnancy rates, breakthrough bleeding, ovulation suppression and hormone pharmacokinetics in women taking oral or vaginal hormonal contraceptives in combination with nonrifamycin antibiotics, including oral, intramuscular and intravenous forms. Oral contraceptives used in the studies included a range of doses and progestins, but lowest-dose pills, such as those containing less than 30 μg ethinyl estradiol or less than 150 μg levonorgestrel, were not included.

The contraceptive formulations in this systematic review1 included oral contraceptive pills, emergency contraception pills and the contraceptive vaginal ring. The effect of antibiotics on other nonoral contraceptives, such as the transdermal patch, injectables and progestin implants was not studied.

Four observational studies1 evaluated pregnancy rates or hormonal contraception failure with any antibiotic use. In two of these four studies, there was no difference in pregnancy rates in women who used oral contraceptives with and without nonrifamycin antibiotics. However, ethinyl estradiol was shown to have increased clearance when administered with dirithromycin (a macrolide).1 Twenty-five of the studies reported measures of contraceptive effectiveness (ovulation) and pharmacokinetic outcomes.

There were no observed differences in ovulation suppression or breakthrough bleeding in any study that combined hormonal contraceptives with an antibiotic. Furthermore, there was no significant decrease in progestin pharmacokinetic parameters during coadministration with an antibiotic.1 Study limitations included small sample sizes and the observational nature of the data.

How would you counsel this patient?

Available evidence suggests that nonrifamycin antibiotics do not diminish the effectiveness of the vaginal contraceptive ring or an oral hormonal contraceptive that contains at least 30 μg of ethinyl estradiol or 150 μg of levonorgestrel. Current guidelines do not recommend the use of additional backup contraception, regardless of hormonal contraception dose or formulation.2 Likewise, the most recent guidance for dental practitioners (i.e., from 2012) no longer advises women to use additional contraceptive protection when taking nonrifamycin antibiotics.3

In our practice, we discuss the option of additional protection when prescribing formulations with lower estrogen doses (< 30 μg), not only because of the limitations of the available data, but also because of the high rates of unintended pregnancy with typical use of combined hormonal contraceptives (9% per year, unrelated to use of antibiotics).2 However, if our patient would rather not use additional barrier methods, she can be reassured that concomitant nonrifamycin antibiotic use is unlikely to affect contraceptive effectiveness.

References

1. Simmons KB, Haddad LB, Nanda K, Curtis KM. Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review. Am J Obstet Gynecol. 2018;218(1):88–97.e14.
2. Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016;65(3):1–103.
3. Taylor J, Pemberton MN. Antibiotics and oral contraceptives: new considerations for dental practice. Br Dent J. 2012;212(10):481–483.

Please note: This abridged article was first published in the Cleveland Clinic Journal of Medicine.