The effect of carbamazepine on etonogestrel concentrations in contraceptive implant users

The objective was to determine the impact of carbamazepine on the pharmacokinetics and pharmacodynamics of the etonogestrel contraceptive implant.

We enrolled healthy, reproductive-age women using an etonogestrel implant for 1-3 years. We measured etonogestrel levels at baseline and following 3 weeks of coadministered carbamazepine titrated up to 300 mg twice daily. We also evaluated for ovarian follicle-like structures and endometrial thickness using transvaginal ultrasound at the baseline and 3-week visits.

We enrolled 13 women; 10 completed study procedures. Participants' mean age was 25.6 years (±5.6), mean body mass index was 30.4 (±7.3), and median duration of implant use was 23 months (range 15-35). The median etonogestrel concentrations before and after carbamazepine coadministration were 158.1 pg/mL (range 128-347) and 50.9 pg/mL (range 39-202), respectively (p=.005). In 8 of 10 subjects, the etonogestrel concentration was below the threshold for ovulatory suppression (<90 pg/mL) after carbamazepine coadministration. The number of ovarian follicle-like structures and endometrial thickness did not significantly change before and after carbamazepine coadministration.

Women using a contraceptive implant experienced significant reductions in etonogestrel concentrations following coadministration of 600 mg of carbamazepine. We did not find significant pharmacodynamic changes during this abbreviated follow-up period.

Carbamazepine use significantly reduces serum etonogestrel concentrations in women using an etonogestrel contraceptive implant, with the majority of participants having etonogestrel concentrations below the threshold for ovulatory suppression. Our findings suggest that treatment with carbamazepine might increase the risk of pregnancy in etonogestrel implant users.