To evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users.
We conducted a prospective, noninferiority study with healthy women using etonogestrel implants continuously for 12–36 months. We measured baseline serum etonogestrel concentrations and then began a 6-week titrated topiramate regimen to standard migraine (100 mg/day) and epilepsy (400 mg/day) dosages. We repeated serum etonogestrel concentrations at 3 weeks (100 mg/day), 4 weeks (200 mg/day), and 6 weeks (400 mg/day) of topiramate therapy. We measured etonogestrel using a validated liquid chromatography-tandem, mass-spectrometry assay and tested for noninferiority (less than 30% decrease) in serum etonogestrel concentrations from baseline.
We enrolled 48 total participants; 32 completed 3 weeks, 31 completed 4 weeks, and 27 completed all follow-up visits. Participants' median age was 25.3 years (range 18.3–37.2), median body mass index (BMI) was 25.5 kg/m2 (range 18.7–42.2), and median duration of implant use was 24 months (range 12–36). Median etonogestrel concentrations were 142 pg/mL (range 76.2–771) at baseline, 126 pg/mL (range 72.4–585) at 3 weeks, 119 pg/mL (range 65.6–542) at 4 weeks, and 105 pg/mL (46.2–859) at 6 weeks. The 95% CIs for mean percent change in serum etonogestrel concentrations from baseline were [−37.3%+16.9%], [−45.4%+5.2%], and [−66.8%+24.8%] at 3 weeks, 4 weeks, and 6 weeks, respectively. Excluding one participant who had a serum etonogestrel concentration less than 90 pg/mL at baseline, 30.8% of participants (8/26, 95% CI 14.3–51.8%) had a serum etonogestrel concentration less than 90 pg/mL at 6 weeks.
Though only a mild enzyme-inducing antiepileptic drug, concomitant topiramate use led to inferior serum etonogestrel concentrations among implant users, with a significant proportion reaching etonogestrel concentrations below the threshold for ovulatory suppression when taking antiepileptic dosages of topiramate.
This study was primarily funded through an Investigator-Initiated Study grant from Merck Sharp & Dohme Corp [MISP#57073]. This work was also supported by NIH/NCATS CTSA Grant Number UL1 TR001082 and NICHD K12 Women's Reproductive Health Research Scholar Program (grant number 5K12HD001271-18).
CLINICAL TRIAL REGISTRATION: