The effect of carbamazepine on the etonogestrel contraceptive implant
Contraception
Awarded 2015
Trainee Grants
Aaron Lazorwitz, MD
University of Colorado
$7,212

Objective: Carbamazepine, a known cytochrome P-450 enzyme inducer, significantly reduces serum hormone levels from oral contraceptives. Despite case reports of contraceptive failure with concomitant use of the etonogestrel contraceptive implant and carbamazepine, no studies have explored the pharmacologic relationship between carbamazepine and non-oral contraceptives. We set out to investigate the pharmacokinetic and pharmacodynamic effects of carbamazepine on the etonogestrel implant. Methods: We enrolled healthy, reproductive-aged women using an etonogestrel implant between one and three years. We collected a baseline serum etonogestrel level and an etonogestrel level following three weeks of co-administered carbamazepine titrated up to 300mg twice daily. A serum carbamazepine level confirmed study compliance. To measure etonogestrel, we used a liquid chromatography-tandem mass spectrometry assay. We compared etonogestrel concentrations before and after carbamazepine exposure with the Wilcoxon-signed rank test. We evaluated pharmacodynamic effects of carbamazepine exposure by measuring ovarian follicle-like structures and endometrial thickness. Results: We enrolled 13 women and 10 were study-compliant. Participants had a mean age of 25.6 years (±5.6), BMI of 30.4 (±7.3), and median duration of implant use of 23 months (range 15-35). The median etonogestrel levels before and after carbamazepine were 158.1pg/mL (range 127.9-347.3) and 50.9pg/mL (range 39.4-202.3) respectively (p=0.005). 80% of participants had etonogestrel levels below the threshold for ovulatory suppression (<90pg/mL) after carbamazepine exposure. We did not identify pharmacodynamic changes. Conclusions: Our study provides evidence that women using an etonogestrel implant while taking carbamazepine have significant reductions in their etonogestrel levels. Our findings strongly suggest that the etonogestrel implant will be less effective for women taking carbamazepine.

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