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.
