Basic Information
ID DDInter1315 and DDInter1834
Interaction Coadministration with topiramate, particularly at dosages above 200 mg/day, may decrease the plasma concentrations and efficacy of contraceptive hormones. The proposed mechanism is topiramate induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of steroidal hormones.
Management The potential for decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients using hormonal contraceptives (including oral, injectable, transdermal, and implantable forms) during treatment with topiramate, particularly at dosages above 200 mg/day. Some clinicians and manufacturers recommend that patients on topiramate dosages at or above 200 mg/day who are taking oral contraceptives should receive a preparation containing no less than 30 or 35 mcg of estrogen, while others recommend at least 50 mcg. Intrauterine systems are unlikely to be significantly affected because of their local action, thus they may be preferable to other routes of administration. Patients should be advised to report any change in their bleeding patterns, although contraceptive efficacy can be decreased even in the absence of breakthrough bleeding. Because use of topiramate can cause fetal harm, it is particularly important that patients not become pregnant during treatment. Counseling should be provided regarding the use of alternative (non-hormonal) or additional (back-up) pregnancy prevention methods during and for at least 28 days after discontinuing topiramate. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed. Alternative, nonenzyme-inducing anticonvulsants that are not believed to interact significantly with hormonal contraceptives include clonazepam, ethosuximide, gabapentin, levetiracetam, pregabalin, tiagabine, valproic acid, vigabatrin, and zonisamide.
References [1] "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn (2001): [2] "Product Information. Topamax (topiramate)." Ortho McNeil Pharmaceutical (2001): [3] Wilbur K, Ensom MHH "Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants." Clin Pharmacokinet 38 (2000): 355-65 [4] Rosenfeld WE, Doose DR, Walker SA, Nayak RK "Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy." Epilepsia 38 (1997): 317-23 [5] Patsalos PN, Froscher W, Pisani F, van Rijn CM "The importance of drug interactions in epilepsy therapy." Epilepsia 43 (2002): 365-85 [6] Doose DR, Wang SS, Padmanabhan M, Schwabe S, Jacobs D, Bialer M "Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects." Epilepsia 44 (2003): 540-9 [7] Nallani SC, Glauser TA, Hariparsad N, et al. "Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate." Epilepsia 44 (2003): 1521-8 [8] Bialer M, Doose DR, Murthy B, et al. "Pharmacokinetic interactions of topiramate." Clin Pharmacokinet 43 (2004): 763-80 [9] "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care 31 (2005): 139-51 [10] Perucca E "Clinically relevant drug interactions with antiepileptic drugs." Br J Clin Pharmacol 61 (2006): 246-255 [11] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [12] Harden CL, Leppik I "Optimizing therapy of seizures in women who use oral contraceptives." Neurology 67(12 Suppl 4) (2006): S56-8 [13] Cerner Multum, Inc. "Australian Product Information." O 0 [14] "Product Information. Qsymia (phentermine-topiramate)." Vivus Inc (2012): [15] Cerner Multum, Inc. "Canadian Product Information." O 0 (2015): [16] "Product Information. Nexplanon (etonogestrel)." Organon Pharmaceuticals (2017): [17] Sunaga T, Cicali B, Schmidt S, Brown J "Comparison of contraceptive failures associated with CYP3A4-inducing drug-drug interactions by route of hormonal contraceptive in an adverse event reporting system." Contraception 103(Issue 4) (2021): 222-4 [18] Doodipala SR "Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives." Expert Rev Clin Pharmacol 3 (2010): 183-92
Alternative for Norgestrel G03F
Megestrol acetate

G03A
Estetrol Megestrol acetate
Alternative for Topiramate N03A
Levetiracetam Paramethadione Ethotoin Vigabatrin Mephenytoin Ganaxolone
Clonazepam Pregabalin Tiagabine Fenfluramine Cannabidiol
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.