Dataset Information

A pilot study on the effect of isotretinoin on serum etonogestrel concentrations in contraceptive implant users.

ABSTRACT:

Objective

To explore the pharmacokinetic interaction between isotretinoin, a cytochrome P-450 (CYP) inducer and potent teratogen, and the etonogestrel contraceptive implant.

Study design

We enrolled healthy reproductive-age women initiating isotretinoin and using an etonogestrel implant. We compared serum etonogestrel concentrations at baseline and after four and nine weeks of isotretinoin co-administration using a validated assay.

Results

Among eight implant users, all serum etonogestrel concentrations remained >90 pg/mL during isotretinoin co-administration with no significant changes from baseline (p = 0.25, Friedman's test).

Conclusion

In this exploratory study, we found that isotretinoin did not cause serum etonogestrel concentrations to fall below the threshold for ovulatory suppression (<90 pg/mL) among implant users.

Implications

Reproductive-age women treated with isotretinoin require reliable contraception to prevent pregnancies impacted by teratogenic-effects. This small study demonstrates that contraceptive implant users maintained serum etonogestrel concentrations above the threshold for consistent ovulatory suppression during isotretinoin co-administration. The contraceptive implant remains an appropriate option for patients considering isotretinoin therapy.

SUBMITTER: Lazorwitz A

PROVIDER: S-EPMC7272275 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users.MethodsWe 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.ResultsWe 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.ConclusionThough 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.Funding sourceThis 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 registrationClinicalTrials.gov, NCT03335163.

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