Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz

Léticée, N.; Viard, Jean‐Paul; Yamgnane, Amina; Karmochkine, Marina; Benachi, Alexandra

doi:10.1016/j.contraception.2011.09.005

Cited by 58 publications

(29 citation statements)

References 16 publications

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“…Interestingly, this patient did not have her Implanon removed and was treated for a subsequent ectopic pregnancy on the contralateral side nine months later (i.e., more than 3 years after initial placement of the implant). A fourth case report describes two different HIV-positive women who conceived intrauterine pregnancies while the etonogestrel implant was in place [30]. One was a 31-year-old HIV-positive women treated with efavirenz, zidovudine and lamivudine.…”

Section: Resultsmentioning

confidence: 99%

Contraception for the HIV-Positive Woman: A Review of Interactions between Hormonal Contraception and Antiretroviral Therapy

Robinson

Jamshidi

Burke

2012

Infectious Diseases in Obstetrics and Gynecology

133

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Background. Preventing unintended pregnancy in HIV-positive women can significantly reduce maternal-to-child HIV transmission as well as improve the woman's overall health. Hormonal contraceptives are safe and effective means to avoid unintended pregnancy, but there is concern that coadministration of antiretroviral drugs may alter contraceptive efficacy. Materials and Methods. We performed a literature search of PubMed and Ovid databases of articles published between January 1980 and February 2012 to identify English-language reports of drug-drug interactions between hormonal contraceptives (HCs) and antiretroviral drugs (ARVs). We also reviewed the FDA prescribing information of contraceptive hormone preparations and antiretrovirals for additional data and recommendations. Results. Twenty peer-reviewed publications and 42 pharmaceutical package labels were reviewed. Several studies of combined oral contraceptive pills (COCs) identified decreased serum estrogen and progestin levels when coadministered with certain ARVs. The contraceptive efficacy of injectable depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) were largely unaffected by ARVs, while data on the contraceptive patch, ring, and implant were lacking. Conclusions. HIV-positive women should be offered a full range of hormonal contraceptive options, with conscientious counseling about possible reduced efficacy of COCs and the contraceptive implant when taken with ARVs. DMPA and the LNG-IUS maintain their contraceptive efficacy when taken with ARVs.

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Section: Resultsmentioning

confidence: 99%

Contraception for the HIV-Positive Woman: A Review of Interactions between Hormonal Contraception and Antiretroviral Therapy

Robinson

Jamshidi

Burke

2012

Infectious Diseases in Obstetrics and Gynecology

133

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“…There are no published reports of the subdermal implant among women with solid organ transplantation. Published reports of pregnancy with concomitant use of subdermal implant and efavirenz, an antiretroviral drug and a CYP450 inducer, suggests that the interaction may lead to a higher likelihood of contraceptive failure in the late second and third years of implant use [21,22]. Until further evidence is published, it is reasonable to balance the proven high efficacy and safety among the general population with the theoretical yet understudied risk among patients taking CYP450-inducing medications.…”

Section: Subdermal Progestin Implantsmentioning

confidence: 95%

Reproductive health care after transplantation

Krajewski¹,

Sucato²

2014

Best Practice & Research Clinical Obstetrics & Gynaecol

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“…Vieira and colleagues reported when the ENG implant was used with EFV-based ART, the ENG median minimum concentration over 24 weeks was 61.9 pg/mL [12], which is below the reported ovulation suppression threshold for ENG of 90 pg/mL [14]. These pharmacokinetic data are supported by an additional six case reports of ENG implant contraceptive failures with combined EFV use [15–18], as well as three recent clinical studies that reported pregnancy rates of 5.5% to 15% in women using LNG contraceptive implants while taking EFV-based ART [13, 19, 20]. A large retrospective cohort reported a pregnancy rate of 3.0 per 100 woman-years (95% CI 1·4–4·7) among women using EFV-based ART with the ENG implant [19].…”

Section: Introductionmentioning

confidence: 92%

Efavirenz decreases etonogestrel exposure

Chappell

Lamorde

Nakalema

et al. 2017

Aids

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Objectives 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 to ART-naïve women over 24 weeks. Design Non-randomized, parallel-group study with 3 arms: ART-naïve, NVP-, or EFV-based ART (N=20 per group). Methods Sparse pharmacokinetic sampling of ENG, NVP or EFV were performed at screening, entry, and then 1, 4, 12 and 24 weeks post-implant insertion. The primary endpoint was ENG concentrations at week 24, compared between the ART-naïve group and each ART group, using geometric mean ratio (GMR) with 90% confidence intervals. Results Sixty participants competed the study and data from 58 participants are included; one participant each was excluded from the NVP group and EFV group due to a sample processing error and ART nonadherence, respectively. At week 24, geometric mean (GM) ENG was 362, 341, and 66 pg/mL in the ART-naïve, NVP, and EFV groups, respectively [GMR: NVP:ART-naïve 0.94 (0.90–1.01); EFV:ART-naïve 0.18 (0.17–0.20)]. NVP and EFV concentrations were lower at week 24 compared to pre-implant [NVP: GM 5.7 versus 6.8 mg/L, respectively, GMR 0.84 (0.83–0.85); EFV: GM 3.6 versus 4.9mg/L, respectively, GMR 0.73 (0.69–0.80)]. Conclusions After 24 weeks of combined use, ENG exposure was 82% lower in women using EFV-based ART compared to ART-naïve 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.

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Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz

Cited by 58 publications

References 16 publications

Contraception for the HIV-Positive Woman: A Review of Interactions between Hormonal Contraception and Antiretroviral Therapy

Contraception for the HIV-Positive Woman: A Review of Interactions between Hormonal Contraception and Antiretroviral Therapy

Reproductive health care after transplantation

Efavirenz decreases etonogestrel exposure

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