NuvaRing does not interact with oral antibiotics

P. Dogterom (1), M.M. van den Heuvel (1), T. Thomsen (2), C. Verhoeven (3)

Department of Clinical Pharmacology and Kinetics, NV Organon, Oss, The Netherlands (1); Pharm PlanNet Contract Research GmbH, Mönchengladbach, Germany (2); Department of Clinical Development, NV Organon, Oss, The Netherlands (3)

Introduction: Oral antibiotics are commonly thought to lower the contraceptive efficacy of combined oral contraceptives, though recent literature suggests a lack of interaction. NuvaRing is a monthly contraceptive vaginal ring that continuously releases 15 µg ethinylestradiol (EE) and 120 µg etonogestrel (ENG) daily. The hormones are absorbed through the vaginal mucosa into the bloodstream, thereby avoiding hepatic first-pass effect. Two trials were conducted to investigate whether serum concentrations of EE and ENG released from NuvaRing are affected by concomitant treatment with the oral antibiotics amoxicillin or doxycycline.

Design and Methods: Two randomized, open-label, crossover trials were performed at a single centre in Germany. In one study, 16 healthy female volunteers (age 18–40 years) were randomized to 21 days of NuvaRing treatment either alone or concomitantly with amoxicillin (875 mg twice daily on days 1–10) followed by a 7-day, ring-free washout, before being crossed over to the alternate treatment. The other study was identical except that doxycycline (100 mg once daily on days 1–10) replaced amoxicillin. Concentrations of circulating EE and ENG were measured over various periods up to and including days 1–22.

Results: Fifteen subjects completed each study. During the relevant treatment periods in both studies, the patterns of circulating EE and ENG concentrations with NuvaRing alone were comparable with those for NuvaRing plus the relevant antibiotic. Analysis of area under the curve (AUC) values (day 1, day 10, days 1–11 and days 1–22) confirmed the absence of pharmacokinetic interactions with both antibiotics. The AUC (mean+SD in ng h/ml) for EE over days 1–22 was similar for NuvaRing with amoxicillin (11.3+3.6) or doxycycline (10.9+3.9) compared with NuvaRing alone (11.7+3.9 and 11.2+3.1, respectively). The AUC (mean+SD in ng h/ml) for ENG over days 1–22 was also comparable for NuvaRing with amoxicillin (992+241) or doxycycline (853+202) and NuvaRing alone (973+193 and 824+149, respectively). NuvaRing was well tolerated in both studies.

Conclusions: The studies show that there is no interaction between EE and ENG administered vaginally with NuvaRing and oral amoxicillin or doxycycline when used concomitantly. Pharmacodynamic and large efficacy studies have previously shown NuvaRing to be a reliable and robust contraceptive method. The present data further support NuvaRing’s reliability since NuvaRing can be used concomitantly with amoxicillin and doxycycline and possibly other broad spectrum oral antibiotics.