Hormonal Contraception in Women Taking Medications with Potential Drug Interactions
Mentor: Eric A. Strand, MD
Editor: Pamela D. Berens, MD
Interactions between hormonal contraceptives and other medications can cause alteration of therapeutic medication level, increased toxicity, and decreased contraceptive efficacy. Combined hormonal contraceptives (CHCs) include products with estrogen and progestin, including oral contraceptives, hormonal patches, and vaginal rings. Progestin only contraceptives (POCs) include progestin only pills (POPs), injectable depot medroxyprogesterone acetate (DMPA), etonorgestrel implants, and levonorgestrel IUDs. Although some medications have been shown to decrease efficacy of CHCs and POCs, the vast majority do not. CHCs, POPs and progestin released by the implant are metabolized via the hepatic cytochrome P450 system. Concomitant use of other drugs that induce enzymes in this system pose the potential for drug interactions. Some antiretrovirals (ARVs), antiepileptic drugs (AEDs) and antibiotics are metabolized via this pathway. The levonorgestrel IUD primarily provides contraception through local endometrial effect, so interactions based on hepatic metabolism are not anticipated.
The ARVs with the most significant concern are non-nucleoside reverse transcriptase inhibitors (specifically efavirenz), ritonavir-boosted protease inhibitors, and protease inhibitors without ritonavir. These interactions might alter safety or decrease overall effectiveness of both the hormonal contraceptive and the ARV drug. This potential decrease in contraceptive efficacy may be less likely with DMPA than other non IUD POCs due to the higher dose of DMPA. Generally, ARV therapy while using a CHC may decrease contraceptive efficacy. If a woman on ARV treatment chooses CHCs, a preparation containing a minimum of 30 µg ethinyl estradiol should be used. Use of fosamprenavir and CHCs may lead to reduced efficacy of the ARV therapy and for this specific medication, the risks of CHC use may outweigh benefits. Atazanavir may increase ethinyl estradiol levels and could result in an increased risk for adverse reactions. Dual contraception (correct and consistent use of condoms with an additional method) is recommended to decrease HIV transmission risk and compensate for possible reduced contraceptive efficacy. There do not appear to be drug interactions between ARVs and IUDs (levonorgestrel or non-hormonal).
Among AEDs, phenytoin, carbamazepine, and phenobarbital are the most potent enzyme inducers. Increased sex hormone binding globulin noted with these medications could reduce the level of free and biologically active hormone. Most research regarding the impact of AEDs on contraceptive metabolism has focused on enhanced estrogen metabolism and reduced efficacy, though some research suggests progestin reduction. Other AED drugs such as topiramate, felbamate, and oxcarbazepine are less potent enzyme inducers but may also decrease effectiveness of CHCs, POPs and the etonorgestrel implant. Effectiveness of DMPA does not appear reduced. Use of these contraceptive methods may decrease the plasma levels of some AEDs, adversely affecting seizure control and potentially requiring an increase in AED dose. Continuous use may avoid fluctuations in serum AED levels and facilitate seizure control. The CDC Medical Eligibility Criteria (MEC) for contraceptive use recommend against the use of CHCs, POPs, and the etonorgestrel implant in patients requiring long term enzyme inducing AEDs. If a CHC is chosen, a minimum 30 µg of ethinyl estradiol should be used. No drug interactions have been reported in women on AEDs using levonorgestrel IUDs.
Rifampin, an antibacterial used to treat tuberculosis and Neisseria meningitidis, is the only antibiotic rated as MEC category 3 (a condition for which risks usually outweigh advantages) for use with CHC, POP, and etonorgestrel implants. Alternate contraception should be considered for long-term users. Other antibiotics have not been shown to decrease contraceptive effectiveness; back-up contraception for women on other antibiotics is not recommended.
Some drugs used to treat cystic fibrosis (specifically lumacaftor) may also reduce non-IUD hormonal contraceptive efficacy by hepatic enzyme induction.
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Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. Morbidity and Mortality Weekly Report July 29, 2016, Vol. 65. No.3. MMWR Recomm Rep. 2016 Jul 29;65(3):1-103. doi: 10.15585/mmwr.rr6503a1.
Nanda K, Stuart GS, Robinson J, et al. Drug Interactions between Hormonal Contraception and Antiretrovirals. AIDS. 2017 Apr 24;31(7):917-952. doi: 10.1097/QAD.0000000000001392.
Reimers A, Brodtkorb E, Sabers A, Interaction between Hormonal Contraceptives and Antiepileptic Drugs: Clinical and Mechanistic Considerations. Seizure. 2015 May;28:66-70. doi: 10.1016/j.seizure.2015.03.006. Epub 2015 Mar 20.
Initial Approval October 2015; Reviewed January 2017, Revised May 2018
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