Dataset Information

Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy.

ABSTRACT: The primary objective of this study was to characterize the pharmacokinetics of etonogestrel (ENG) released from a contraceptive implant in Ugandan women living with HIV who were receiving efavirenz (EFV) or nevirapine (NVP)-based antiretroviral therapy (ART), compared with ART-naive women over 24 weeks.Nonrandomized, parallel-group study with three arms: ART-naive, NVP, or EFV-based ART (N?=?20/group).Sparse pharmacokinetic sampling of ENG, NVP, or EFV were performed at screening, entry, and then 1, 4, 12, and 24-week postimplant insertion. The primary endpoint was ENG concentrations at week 24, compared between the ART-naive group and each ART group, using geometric mean ratio (GMR) with 90% confidence intervals.Sixty participants competed the 24-week study and data from 58 participants are included; one participant each was excluded from the NVP group and EFV group because of a sample processing error and ART nonadherence, respectively. At week 24, geometric mean ENG was 362, 341, and 66?pg/ml in the ART-naive, NVP, and EFV groups, respectively [GMR: NVP?:?ART-naive 0.94 (0.90-1.01); EFV?:?ART-naive 0.18 (0.17-0.20)]. NVP and EFV concentrations were lower at week 24 compared to preimplant [NVP: geometric mean 5.7 versus 6.8?mg/l, respectively, GMR 0.84 (0.83-0.85); EFV: geometric mean 3.6 versus 4.9?mg/l, respectively, GMR 0.73 (0.69-0.80)].After 24 weeks of combined use, ENG exposure was 82% lower in women using EFV-based ART compared with ART-naive women. In contrast, NVP did not significantly impact ENG exposure. These results raise concerns about reduced effectiveness of implantable contraception for women taking EFV-based ART.

SUBMITTER: Chappell CA

PROVIDER: S-EPMC5578871 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy.

Chappell Catherine A CA Lamorde Mohammed M Nakalema Shadia S Chen Beatrice A BA Mackline Hope H Riddler Sharon A SA Cohn Susan E SE Darin Kristin M KM Achilles Sharon L SL Scarsi Kimberly K KK

AIDS (London, England) 20170901 14

<h4>Objectives</h4>The primary objective of this study was to characterize the pharmacokinetics of etonogestrel (ENG) released from a contraceptive implant in Ugandan women living with HIV who were receiving efavirenz (EFV) or nevirapine (NVP)-based antiretroviral therapy (ART), compared with ART-naive women over 24 weeks.<h4>Design</h4>Nonrandomized, parallel-group study with three arms: ART-naive, NVP, or EFV-based ART (N = 20/group).<h4>Methods</h4>Sparse pharmacokinetic sampling of ENG, NVP, ...[more]

PMID: 28692531

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Project description:ObjectiveWe evaluated the pharmacokinetics of double-dose levonorgestrel (LNG) implants to overcome the drug-drug interaction with efavirenz-based antiretroviral therapy (ART).Study designWe conducted a nonrandomized, open-label, parallel-group, longitudinal pharmacokinetic study among Ugandan women ages 18-45 years. Participants with HIV on ART containing efavirenz 600 mg received 300 mg of LNG implants (Jadelle®, Bayer, New Zealand): 300LNG+ART group. We compared our outcomes with women without HIV using standard dose, 150 mg of LNG implants: 150LNG group. The implant was placed on day zero in both groups, and we quantified plasma LNG concentrations over 48 weeks post implant insertion. LNG pharmacokinetic parameters were estimated using noncompartmental techniques. Our primary outcome was the geometric mean ratio with 90% confidence intervals of LNG area under the concentration-time curve over 24 weeks (AUC0-24w) between groups. Demographic data were described as median (interquartile range). A secondary outcome compared between-group percent of LNG concentrations ≥300 pg/mL, a minimum threshold selected a priori based on observed pregnancies in Ugandan women on standard-dose LNG implants plus efavirenz.ResultsWe enrolled 27 women in the 300LNG+ART group (34 [28.0 to 40.5] years and 61.0 [49.8-66.0] kg) and 19 women in the 150LNG group (33 [30.0 to 34.5] years and 64.9 [59.0 to 74.5] kg). LNG AUC0-24w was 34% lower for 300LNG+ART versus 150LNG (geometric mean 9998 vs. 15,231 pg*week/mL, respectively [geometric mean ratio 0.66 (90% confidence intervals, 0.54 to 0.80)]). The percentage of participants with LNG concentrations ≥300 pg/mL was not statistically different between groups at week 24 (300LNG+ART: 74.1%; 150LNG: 89.5%; p = 0.27).ConclusionDouble-dose LNG implant did not completely overcome the drug-drug interaction with efavirenz.ImplicationIn women using ART containing efavirenz, placing two implant systems (300 mg) did not normalize LNG pharmacokinetics compared with the standard-dose implant (150 mg), and some women had evidence of ovulatory activity. Alternative ART without drug-drug interactions, such as dolutegravir, is recommended with contraceptive implants.

Dataset Information

Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy.

Publications

Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy.

Similar Datasets

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