Effects of concurrent vaginal miconazole treatment on the absorption and exposure of Nestorone® (segesterone acetate) and ethinyl estradiol delivered from a contraceptive vaginal ring: a randomized, crossover drug–drug interaction study

Katharine B. Simmons, Narender Kumar, Marlena Plagianos, Kevin Roberts, Elena Hoskin, Leo Han, Mohcine Alami, George Creasy, Bruce Variano, Ruth Merkatz

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objectives: To evaluate the effects of concurrent administration of three vaginal miconazole nitrate formulations on the absorption and exposure of Nestorone® (segesterone acetate) and ethinyl estradiol from a novel contraceptive vaginal ring (NES/EE CVR). Study design: This was an open-label, randomized, crossover, drug–drug interaction study conducted over three menstrual cycles in healthy women with regular menses. We compared systemic exposure to NES and EE by determining area under the curve (AUC 8–21d ) with CVR only and CVR with each miconazole treatment. Three different miconazole formulations (single-dose suppository, multiple-dose suppository or multiple-dose cream) were administered in a single dose on day 8 or multiple doses on days 8–10 after CVR insertion. We evaluated safety and tolerability of the CVR in the presence of antimycotic comedication. Results: Forty-five participants were randomized, and 29 completed participation. Systemic exposure to NES and EE released from the CVR increased with single or multiple doses of miconazole suppositories but not with multiple-dose cream. The maximum EE geometric mean ratio (GMR) for AUC 8–21d was 1.67 (1.51–1.86) for single-dose and 1.42 (1.21–1.66) for multiple-dose suppositories. By contrast, systemic exposure to NES and EE was comparable with and without miconazole cream (all GMRs and confidence intervals within 0.80 to 1.25). Adverse events (AEs) were similar with CVR only and with all miconazole treatment groups. There were no serious treatment-related AEs. Conclusions: Miconazole vaginal suppositories were associated with increased systemic levels of NES and EE, while systemic exposure with miconazole vaginal cream was comparable to no miconazole exposure. Implications: Coadministration of miconazole suppositories with the investigational NES/EE CVR led to higher systemic exposure of both hormones, while coadministration with miconazole cream did not affect hormone levels. Women utilizing the NES/EE CVR may be advised to use an oral formulation or miconazole cream rather than suppository to treat vaginal candidiasis.

Original languageEnglish (US)
Pages (from-to)270-276
Number of pages7
JournalContraception
Volume97
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Antifungal
  • Contraceptive vaginal ring
  • Ethinyl estradiol (EE)
  • Miconazole
  • Nestorone (NES)
  • Systemic exposure

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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