- Case Report
- Open Access
Etonogestrel contraceptive implant failure in a woman taking rifampin: a case report
Contraception and Reproductive Medicine volume 7, Article number: 5 (2022)
The etonogestrel subdermal implant is the most efficacious hormonal contraceptive currently available and provides 99.7% effective contraception. However, similar to other hormonal contraception, its effectiveness is compromised with the use of cytochrome P450 inducing drugs resulting in an unplanned pregnancy. Despite this risk, little is known about the outcome of concomitant use of rifampin and contraceptive implants.
A 24-year-old woman was provided with an etonogestrel implant in September 2018. In July 2020, she was started with rifampin based anti-tuberculosis for tuberculosis of the lymph nodes. In December 2020, she presented to the family planning clinic of St. Paul’s Hospital Millennium Medical college with a diagnosis of failed implant and second-trimester pregnancy at a gestational age of 19 weeks. The etonogestrel implant was removed and the patient was linked to antenatal care follow up.
Concomitant use of hepatic cytochrome P450 enzyme-inducing medications with certain hormonal contraceptives may reduce effectiveness resulting in unintended pregnancy. Women should be given detailed counseling about the potential for drug interactions and a multidisciplinary approach with consultation or referral to reproductive health specialists is crucial for optimal management of women who are at increased risk of contraceptive failure and unintended pregnancy.
Contraceptive implants are among the most effective long-acting reversible contraceptive (LARC) methods . Nexplanon® is a progestin-only, single-rod contraceptive implant containing 68 mg of etonogestrel placed in the inner side of the non-dominant upper arm . The mechanism of action is mainly through suppression of ovulation augmented by increased cervical mucus viscosity that hinders the passage of spermatozoa . Etonogestrel implant is the most efficacious hormonal contraceptive currently available and provides 99.7% effective contraception for up to three years [4, 5].
Cytochrome P450 enzyme (CYP450) inducing medications are reported to be one of the reasons for the failure of this highly effective contraceptive method. For example, rifampin, a highly effective anti-Tuberculosis (TB) drug, induces activation of CYP450. Cytochrome P450 in turn reduces contraception effectiveness by increasing serum clearance and making the hormonal contraception less available in the serum to prevent pregnancy [6, 7]. Similarly, other CYP450 enzyme inducing medications such as carbamazepine and efavirenz had resulted in a failure of etonogestrel implant [8, 9].
In this report, we present a case of failed etonogestrel implant that highlights the importance of client counseling about the possibility of drug interactions between hormonal contraception and rifampin-based anti-TB medications.
In September 2018, a 24-year-old woman had an uncomplicated vaginal delivery at St. Paul’s Hospital Millennium Medical College (SPHMMC). Following her delivery, she was counseled on possible options of contraception by the attending doctor and opted for etonogestrel implant since she wanted to delay pregnancy for a minimum of three years. After reviewing her medical eligibility and excluding contraindications, a trained provider placed Nexplanon® (Merck & Co. Inc., Whitehouse Station, NJ) in the left arm as per insertion protocol. She noticed a reduction in the frequency and amount of menstrual bleeding after the first year of use. Otherwise, there were no side effects of the contraceptive device reported by the patient.
In July 2020, she was started on anti-TB drugs for the diagnosis of TB lymphadenitis. The treatment regimen consisted of rifampin, isoniazid, pyrazinamide, and ethambutol once daily for two months followed by a four-month course of daily rifampin and isoniazid.
During the initiation of anti-TB treatment, she claims that she was reassured by the health care provider about the effectiveness of etonogestrel implant and started the treatment without being informed about the possibility of drug interactions and unintended pregnancy. She was not advised to change the contraception method or use an additional method.
In November 2020, she went to a nearby health center after missing her menstrual period for four consecutive months. A pregnancy test was positive for which she was referred to SPHMMC with a diagnosis of second-trimester pregnancy and failed etonogetrel implant. Upon arrival to SPHMMC in December 2020, the patient had stable vital signs, and obstetric ultrasound showed a 19 weeks pregnancy with a normal fetal gross anatomical appearance. She expressed interest in continuing the pregnancy and was reassured about the lack of untoward effects from the contraceptive method on the fetus and the pregnancy. The etonogestrel implant was localized and removed from her left upper arm. She then attended regular antenatal care follow up.
The etonogestrel implant is one of the most effective LARC methods. In most healthy women it is more than 99% effective with a failure rate lower than permanent sterilization techniques [1, 5, 10]. Several factors have been implicated in the failure of implant contraceptives. In a review of more than 200 unintended pregnancies among women using etonogestrel implant, improper insertion was the most common reason for method failure accounting for 38% of cases whereas 4% of cases were due to drug interactions . Another large study however showed that a large proportion of contraceptive failure (nearly 25%) was associated with intake of drugs that can potentially affect contraceptive efficacy .
Etonogestrel is metabolized by the hepatic CYP450 enzyme system. Drugs that induce CYP450 may increase the rate of hepatic degradation, leading to a lower bioavailability and potential loss of contraceptive effect . For example, a pharmacologic study of women using etonogestrel implant showed a drop in the serum etonogestrel level below the threshold needed to inhibit ovulation after administration of carbamazepine, which is known to induce CYP450 enzymes . Similar findings of drug interactions and failed implants were reported among women on other anti-epileptic, antiretroviral, and anti-TB drugs [7, 15, 16]. This patient was started on an anti-TB regimen containing rifampin, a known CYP450 enzyme inducer .
For women who are using or planning to use hormonal contraceptives, several considerations need to be made should they require treatment with medications that are CYP450 enzyme inducers. A multidisciplinary approach with consultation or referral to reproductive health specialists can play a significant role in optimal management. They need to receive detailed counseling about the potential for drug interaction. The discussion should include the use of other alternative methods. Both the World Health Organization and United States Center for Disease Control medical eligibility criteria recommend women on implants who need long-term treatment with rifampin to use other contraceptive methods [17, 18]. The United Kingdom (UK MEC) advises the use of additional barrier methods or a switch to other methods when the potential for drug interactions is a concern [19, 20]. The product label for Nexplanon® also indicates that rifampin reduces the effectiveness of etonogestrel contraceptive implants .
This case report highlights the need for detailed contraceptive counseling for women with medical comorbidities. Health care providers should be aware of the possible reduced effectiveness of certain hormonal contraceptives due to concomitant use of hepatic CYP450 enzyme-inducing medications. Alternative contraceptive options should be offered in these cases. Thorough medical and contraceptive history with consultation or referral to reproductive health specialists is crucial for optimal management of women who are at increased risk of contraceptive failure and unintended pregnancy.
Availability of data and materials
All data materials related to the case report are included in the manuscript.
Medical eligibility criteria
St. Paul’s Hospital Millennium Medical College
World Health Organization Department of Reproductive Health and Research (WHO/RHR), Johns Hopkins Bloomberg School of Public Health/Center for Communication Programs (CCP), Knowledge for Health Project. Family Planning: A Global Handbook for Providers (2018 update). Baltimore and Geneva: CCP and WHO; 2018.
Mansour D. Nexplanon®: what Implanon® did next. J Fam Plann Reprod Health Care. 2010;36:187–9.
Croxatto HB. Mechanisms that explain the contraceptive action of progestin implants for women. Contraception. 2002;65:21–7.
Palomba S, Falbo A, Di Cello A, Materazzo C, Zullo F. Nexplanon: the new implant for long-term contraception. Compr Descriptive Rev, Gynecol Endocrinol. 2012;28(9):710–21.
Mommers E, Blum G-F, Gent TG, Peters KP, Sordal TS, Marintcheva-Petrova M. Nexplanon, a radiopaque etonogestrel implant in combination with a next-generation applicator: 3-year results of a noncomparative multicenter trial. Am J Obstet Gynecol. 2012;207(5):388-e6.
Zhang N, Shon J, Kim M, Yu C, Zhang L, Huang S, et al. Role of CYP3A in Oral Contraceptives Clearance. Clin Transl Sci. 2018;11:251–60.
Gbolade B. Failure of Implanon® on antituberculous therapy. Open Access J Contracept. 2010;1:103–5. https://doi.org/10.2147/OAJC.S12194.
Schindlbeck C, Janni W, Friese K. Failure of Implanon contraception in a patient taking carbamazepin for epilepsia. Arch Gynecol Obstet. 2006;273(4):255–6.
Leticee N, Viard JP, Yamgnane A, et al. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception. 2012;85:425–7.
Trussell J, Aiken ARA, et al. Contraceptive efficacy. In: Hatcher RA, et al., editors. Contraceptive Technology, 21st revised edition. New York: Ardent Media; 2018.
Harrison-Woolrych M, Hill R. Unintended pregnancies with the etonogestrel implant (Implanon): a case series from postmarketing experience in Australia. Contraception. 2005;71:306–8.
Graesslin O, Korver T. The contraceptive efficacy of Implanon®: A review of clinical trials and marketing experience. Eur J Contracept Reprod Health Care. 2008;13(s1):4–12.
Perry R, Stone RH, Haider S. Medication interactions with contraceptives. In: Allen RH, Cwiak CA, editors. Contraception for the medically challenging patient. New York: Springer Science + Business Media; 2014. p. 347–62.
Lazorwitz A, Davis A, Swartz M, Guiahi M. The effect of carbamazepine on etonogestrel concentrations in contraceptive implant users. Contraception. 2017;95:571–7.
Kumbeni MT, Apanga PA, Ayamga EA. Nexplanon failure in a woman with HIV infection in rural Ghana: A case report. Clin Case Rep. 2020;8(12):2369–72.
Lange J, Teal S, Tocce K. Decreased efficacy of an etonogestrel implant in a woman on antiepileptic medications: a case report. J Med Case Reports. 2014;8:43. https://doi.org/10.1186/1752-1947-8-43.
World Health Organization. 2015 Medical Eligibility Criteria for Contraceptive Use. 5th Edition. Geneva: World Health Organization; 2015. Available from: https://www.who.int/publications/i/item/9789241549158 (Accessed on 24 Dec 2020).
Centers for Disease Control and Prevention. US Medical Eligibility Criteria (US MEC) for contraceptive use. USA: Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion; 2016.
UKMEC April 2016 (Amended September 2019) - Faculty of Sexual and Reproductive Healthcare n.d. https://www.fsrh.org/standards-and-guidance/documents/ukmec-2016/ (Accessed 2 Jan 2021).
Drug Interactions - Faculty of Sexual and Reproductive Healthcare n.d. https://www.fsrh.org/standards-and-guidance/fsrh-guidelines-and-statements/drug-interactions/ (Accessed 2 Jan 2021).
Merck. Nexplanon Full Prescribing Information 2020. https://www.merck.com/product/usa/pi_circulars/n/nexplanon/nexplanon_pi.pdf (Accessed Feb 2021)
We want to thank our patient for her consent in allowing us to share her experience as well as all health care providers who are involved in her care. We also thank the department of obstetrics and gynecology of St. Paul’s Hospital Millennium Medical College.
The research did not receive a grant or any form of support from funding agents or authorities.
Ethics approval and consent to participate
Ethical clearance was obtained from the Institutional Research and Ethics Review Committee (IRB) of St. Paul’s Hospital Millennium Medical College for publication of the case report.
Consent for publication
Informed and written consent was taken from the patient to publish the case report.
All authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Tufa, T.H., Fessehaye, A. & Abubeker, F.A. Etonogestrel contraceptive implant failure in a woman taking rifampin: a case report. Contracept Reprod Med 7, 5 (2022). https://doi.org/10.1186/s40834-022-00172-1
- Etonogestrel implant
- Contraceptive failure
- Unintended pregnancy
- Case report