Oral Contraceptive Drug Interactions

Oral contraceptives are the most commonly used contraceptive method in the United States.  We are often asked about efficacy, missed pills, and return to fertility; however, it’s important to keep drug interactions in mind, too.  Below is a non-exhaustive list of common combined oral contraceptive drug interactions.

Liver enzyme-inducing drugs

Drugs that induce the cytochrome P450 (CYP) liver enzymes, specifically CYP3A, commonly interact with combined oral contraceptives (COC).  Examples include carbamazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampicin, St. John’s wort, and topiramate (topiramate may be safe in doses less than 200 mg per day in nonobese women).

CYP3A inducers decrease plasma concentration of COC by increasing metabolism, resulting in reduced efficacy which could lead to breakthrough bleeding or even unintended pregnancy.  This interaction can continue for up to 28 days following discontinuation of the liver enzyme-inducing drug. 

For short-term use of a liver enzyme-inducing drug, recommend back-up barrier contraception during liver enzyme-inducing drug use and for 28 days following discontinuing, and recommend a COC containing ≥ 30 mcg (0.03 mg) of ethinyl estradiol (EE).  For long-term use of a liver enzyme-inducing drug, recommend an alternative contraceptive method, such as an intrauterine device (IUD).


In contrast to liver enzyme-inducing drugs, the lamotrigine interaction concerns plasma levels of lamotrigine itself.  Estrogen induces the metabolism of lamotrigine, resulting in up to 50% decreased lamotrigine concentration and reduced seizure control.  Maintenance doses of lamotrigine may need to be increased 2-fold, and more frequent monitoring of plasma levels and clinical response may be valuable until patients find a stable dose.  Lamotrigine levels will increase during the placebo week, which may result in adverse effects such as dizziness.  

Ulipristal acetate (UPA) Ella®

Ulipristal acetate (UPA), or Ella®, is an emergency contraceptive that works by blocking progesterone.  COCs may reduce the efficacy of UPA in delaying ovulation, and UPA may reduce the efficacy of COCs. Because of this two-way interaction, women should wait 5 days after taking UPA before starting a COC and should use a barrier method until their next menstrual period.

Diarrhea or Vomiting

The last example may not be a true drug interaction in a sense but we will still put it on the list of oral contraceptive drug interactions. Drugs or conditions which cause severe diarrhea or vomiting can reduce the absorption of COCs.  Examples include antibiotics, antiobesity drugs, or acute illness.  In the event of vomiting especially, women may need to follow guidance for missed pills.

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This article was written by Sarah Jackson, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCGP, BCPS

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DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. T116852, Oral Contraceptives; [updated 2018 Nov 30, cited June 7, 2021]. Available from https://www.dynamed.com/topics/dmp~AN~T116852. Registration and login required.

IBM Micromedex® Drug Interaction Checking (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.ezp3.lib.umn.edu/ (accessed: June 7, 2021).

Lamictal®, lamotrigine extended release tablet. Par Pharmaceutical, Inc. Chestnut Ridge, NY. April 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fb59c76a-9b6f-40ea-ac3a-58c3195c4377



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Written By Eric Christianson

June 16, 2021

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