Topiramate with Levonorgestrel Interaction Details

Brand Names Associated with Topiramate

Brand Names Associated with Levonorgestrel

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Reduced contraceptive efficacy and an increased risk of breakthrough bleeding

Interaction Summary

Concomitant use of topiramate and combination oral contraceptives may result in decreased contraceptive efficacy and increased breakthrough bleeding, especially with contraceptives at doses greater than 200 mg/day. Advise patients to report any changes in their bleeding patterns if topiramate is used concomitantly with estrogen-containing or progestin only contraceptives. Patients should use additional contraception or an alternate nonhormonal contraceptive method  during coadministration and for at least 28 days after discontinuation of topiramate . An expert Working Group that was convened by the WHO in 2008 to revise the third edition of the Medical Eligibility Criteria for Contraceptive Use recommended patients avoid the concomitant use of topiramate with combined oral contraceptives, the transdermal patch, the vaginal ring, or progestin-only pills due to the risk of decreased contraceptive efficacy .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of topiramate and combination oral contraceptives may result in decreased contraceptive efficacy and increased breakthrough bleeding, especially with contraceptives at doses greater than 200 mg/day. Advise patients to report any changes in their bleeding patterns if topiramate is used concomitantly with estrogen-containing or progestin only contraceptives. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding. In women who are taking topiramate concomitantly with hormonal contraceptives, including combination and progestin-only contraceptives, recommend the patient use additional contraception or alternate contraceptive method  during coadministration and for at least 28 days after discontinuation of topiramate .

Mechanism Of Interaction

Increased metabolism of hormonal contraceptive

Literature Reports

A) Topiramate significantly decreased serum etonogestrel concentrations following 6 weeks of concomitant use in a prospective, non-inferiority study of healthy females of reproductive potential (median age, 25.3 years) who had received etonogestrel implants continuously for a median duration of 24 months (range, 12 to 36 months) (n=32 evaluable). Median serum etonogestrel concentrations were 142 picogram (pg)/mL at baseline and 105 pg/mL at visit 4 (end of the sixth week topiramate titration schedule). Mean percent change in serum etonogestrel concentration was -37.3% at visit 2 (end of third week of topiramate titration), -45.4% at visit 3 (end of fourth week of topiramate titration), and -66.8% at visit 4. Serum etonogestrel concentrations significantly decreased with increasing topiramate therapy. Excluding 1 participant with a serum etonogestrel concentration less than 90 pg/mL at baseline, 30.8% of patients had a serum etonogestrel concentration of less than 90 pg/mL at the maximum topiramate dose for visit 4. Topiramate was titrated over 6 weeks to a maximum dose of 200 mg twice daily by the final week. Patients receiving other CYP3A4 inducers or inhibitors were excluded .

B) A randomized, open-label, 5-group study in healthy volunteers concluded that topiramate doses less than or equal to 200 mg/day do not interact with oral contraceptives containing ethinyl estradiol and norethindrone. In two 28-day cycles, 5 groups of female subjects received oral doses of ethinyl estradiol/norethindrone (Ortho-Novum(R) 1/35) alone in the first cycle and then in combination with topiramate or carbamazepine during the second cycle. Coadministration of daily topiramate in nonobese (50 mg, n=11; 100 mg, n=10; 200 mg, n=12) and obese (BMI 30 to 35; n=12; topiramate 200 mg) women resulted in nonsignificant changes in the AUC of ethinyl estradiol and nonsignificant changes in the AUC and plasma concentrations of norethindrone compared with the contraceptive alone. When carbamazepine 600 mg/day was coadministered with ethinyl estradiol/norethindrone (n=10), significant decrease in AUC of each drug was observed; 42% and 58%, respectively. Carbamazepine increased oral clearance in both contraceptives by 127% and 69%, respectively .

C) In a study of 12 women with epilepsy who were receiving stable valproic acid monotherapy and oral contraception with ethinyl estradiol 35 mcg/norethindrone 1 mg (21 days on/7 days off), the coadministration of topiramate (200 to 800 mg/day) for four 28-day cycles significantly decreased systemic exposure to ethinyl estradiol. Starting on the first 3 days of cycle 2 through cycle 4, topiramate 100 mg, 200 mg, and 400 mg were given twice daily, respectively. Although, the addition of topiramate did not change the norethindrone pharmacokinetic parameters, the mean AUC of ethinyl estradiol was decreased by 18%, 21%, and 30% with daily topiramate doses of 200 mg, 400 mg, and 800 mg, respectively, in cycles 2 through 4 compared with cycle 1 (control cycle) and mean serum clearance (CL/F) of ethinyl estradiol was 14.7% to 33% higher. It is suggested that the modest effect of topiramate on ethinyl estradiol pharmacokinetics may be due to topiramate being a weak inducer of cytochrome P450 .

Topiramate Overview

• Topiramate is used alone or with other medications to treat certain types of seizures including primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) and partial onset seizures (seizures that involve only one part of the brain). Topiramate is also used with other medications to control seizures in people who have Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). Topiramate is also used to prevent migraine headaches but not to relieve the pain of migraine headaches when they occur. Topiramate is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the brain.

Levonorgestrel Overview

• Levonorgestrel is used to prevent pregnancy after unprotected sexual intercourse (sex without any method of birth control or with a birth control method that failed or was not used properly [e.g., a condom that slipped or broke or birth control pills that were not taken as scheduled]). Levonorgestrel should not be used to prevent pregnancy on a regular basis. This medication is to be used as an emergency contraceptive or backup in case regular birth control fails or is used incorrectly. Levonorgestrel is in a class of medications called progestins. It works by preventing the release of an egg from the ovary or preventing fertilization of the egg by sperm (male reproductive cells). It also may work by changing the lining of the uterus (womb) to prevent development of a pregnancy. Levonorgestrel may prevent pregnancy, but it will not prevent the spread of human immunodeficiency virus (HIV, the virus that causes acquired immunodeficiency syndrome [AIDS]) and other sexually transmitted diseases.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.