Dataset Information

Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48 weeks with rilpivirine- or darunavir-based antiretroviral therapy.

ABSTRACT:

Background

Pharmacokinetic data are lacking for progestin-releasing subdermal contraceptive implants when used with either rilpivirine- or darunavir/ritonavir-based ART.

Objectives

To characterize the pharmacokinetics of etonogestrel or levonorgestrel implants when administered with these ART regimens over 48 weeks.

Patients and methods

Two separate, parallel, three-group, non-randomized, pharmacokinetic studies evaluated either etonogestrel or levonorgestrel in women receiving rilpivirine- or darunavir-based ART compared with women without HIV (control group). Participants on ART were switched to rilpivirine-based ART with a run-in period of 6 weeks or darunavir-based ART with a run-in of 2 weeks prior to implant insertion. Plasma was collected on Day 0, and 1, 4, 12, 24, 36 and 48 weeks post-insertion. Plasma progestin concentrations were compared between ART and control groups by geometric mean ratio (GMR) and 90% CI.

Results

At the primary endpoint of Week 24, progestin concentrations were similar between the rilpivirine and control groups [etonogestrel: 1.18 (0.99-1.37); levonorgestrel: 1.16 (0.97-1.33)]. At Week 24, progestin exposure was higher in the darunavir groups compared with the control group [etonogestrel: 2.56 (1.69-3.28); levonorgestrel: 1.89 (1.38-2.29)]. Results remained consistent through to Week 48. No differences in etonogestrel-related adverse events were observed, but both ART groups experienced more menstrual abnormalities versus the control group with levonorgestrel.

Conclusions

Etonogestrel and levonorgestrel concentrations were not altered by rilpivirine-based ART. Although progestin concentrations were higher in the ART groups containing ritonavir-boosted darunavir, no implant-related serious adverse events were observed. Both progestin-releasing implants are an appropriate contraceptive option with either rilpivirine- or darunavir/ritonavir-based ART.

SUBMITTER: Nakalema S

PROVIDER: S-EPMC10205603 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48 weeks with rilpivirine- or darunavir-based antiretroviral therapy.

Nakalema Shadia S Chappell Catherine A CA Pham Michelle M Byakika-Kibwika Pauline P Kaboggoza Julian J Walimbwa Stephen I SI Musaazi Joseph J Nakijoba Ritah R Mbabazi Leah L Kyohairwe Isabella I Nassiwa Sylvia S Jeppson Jeffrey J Winchester Lee L Siccardi Marco M Fletcher Courtney V CV Scarsi Kimberly K KK Lamorde Mohammed M

The Journal of antimicrobial chemotherapy 20221001 11

<h4>Background</h4>Pharmacokinetic data are lacking for progestin-releasing subdermal contraceptive implants when used with either rilpivirine- or darunavir/ritonavir-based ART.<h4>Objectives</h4>To characterize the pharmacokinetics of etonogestrel or levonorgestrel implants when administered with these ART regimens over 48 weeks.<h4>Patients and methods</h4>Two separate, parallel, three-group, non-randomized, pharmacokinetic studies evaluated either etonogestrel or levonorgestrel in women recei ...[more]

PMID: 36059130

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Project description:ObjectivesLong-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics.Study designWe enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrel concentrations between antiretroviral regimens. We considered a minimum serum etonogestrel concentration of 90 pg/mL adequate for ovulation suppression.ResultsWe collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion.ConclusionsUnlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations.ImplicationsThe findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.

Project description:BackgroundEtonogestrel and levonorgestrel implants are effective for 3 and 5 years of contraception, respectively. The removal of contraceptive implants before the due date, also known as implant early discontinuation, contributes to unplanned pregnancies, which can lead to unfavourable reproductive health outcomes, especially in adolescents. We aimed to assess the magnitude of early implant discontinuation among those who initiated the method at our hospital, and to compare this rate between adolescents and adults.MethodsThis retrospective cohort study reviewed the medical records of participants who initiated contraceptive implants from January 2014 to December 2019 at King Chulalongkorn Memorial Hospital. Early discontinuation was defined as the removal of implants prior to the due date. Cox proportional hazard regression analysis was performed to identify factors associated with early discontinuation.ResultsOur analysis included 1,435 participants, 409 of whom were adolescents. Levonorgestrel implants were used by 53.3% of the participants(68.7% and 47.1% of adolescents and adults, respectively); the remainder used etonogestrel implants. The total early discontinuation rate was 19.3%, which was comparable between the two implant types. The most common reason for discontinuation was intolerance of side effects, with abnormal bleeding being the most frequent. Adolescents were less likely to discontinue implants early (HR 0.72, 95% CI = 0.55-0.95). Factors significantly associated with decreased early discontinuation were: free-of-charge implants (HR 0.75, 95% CI = 0.58-0.95), continuous users of implants (HR 0.56, 95% CI = 0.36-0.86), postpartum status during implant initiation (HR 0.77, 95% CI = 0.60-0.98), and participants with children (HR 0.77, 95% CI = 0.60-0.99).ConclusionCompared with adults, adolescents were less likely to discontinue contraceptive implants before the due date. Participants who received free implants, continuous users who had previously used implants, postpartum insertion, and having children were associated with less early discontinuation. Our findings supports continued government funding for free implants in Thailand.

Dataset Information

Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48 weeks with rilpivirine- or darunavir-based antiretroviral therapy.

Background

Objectives

Patients and methods

Results

Conclusions

Publications

Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48 weeks with rilpivirine- or darunavir-based antiretroviral therapy.

Similar Datasets

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