Anti-Epileptic Drugs and Hormonal Treatments
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Epilepsy and the medications used in its treatment are known to affect the menstrual cycle, aspects of contraception, and bone health in women. Adolescence is an important time to review the diagnosis of both epilepsy and the epilepsy syndrome because of the implications and decisions, which should be made regarding antiepileptic drug (AED) treatment. In girls, once they are on AED therapy, seizure free, and driving, it becomes difficult to change therapy because of the risk of breakthrough seizures and the fact that the new AED may not be as effective as the first. So a treatment choice made in adolescence is often life-long. Therefore, women need to be started on an AED that currently appears to be the most suitable for their seizure type, has a low teratogenic risk, and hopefully does not interact with contraception. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Nonenzyme-inducing AEDs (valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine, and zonisamide) do not show any interactions with the combined oral contraceptive. There are interactions between the combined oral contraceptive and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages >200 mg/day], oxcarbazepine, eslicarbazepine and perampanel [dosages >12 mg/day]) and lamotrigine. Women taking enzyme inducing AEDs should be encouraged to use a method of contraception that is unaffected by their epilepsy medication. Interactions between AEDs and other hormonal therapies are less well studied. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis, and osteomalacia. No studies have been undertaken looking at preventative therapies for these comorbidities. This article will concentrate on current contraceptive treatment options in patients taking AEDs.
KeywordsEpilepsy Anti-epileptic drugs Phenobarbitone Phenytoin Sodium valproate Lamotrigine Carbamazepine Oxcarbazepine Eslicarbazepine Gabapentin Pregabalin Tiagabine Topiramate Zonisamide Benzodiazepines Ethosuximide Perampanel Hormones Contraception Oral contraceptive pill Medroxyprogesterone Norethisterone Levonorgestrel implants Intra-uterine contraceptive device Contraceptive implant
Compliance with Ethics Guidelines
Conflict of Interest
Clare A. Johnston has had travel/accommodations expenses covered/reimbursed by Pfizer. Pamela M. Crawford has had travel/accommodations expenses covered/reimbursed by UCB and Eisai.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
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- 5.••Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Statement. Update on newer antiepileptic and antiretroviral drugs and interactions with hormonal contraceptives. 2013. Available at: http://www.fsrh.org/pdfs/CEUstatementUpdateNewerAntiepilepticAntiretroviralDrugs.pdf Accessed December 21, 2013. Updated hormonal contraceptive guidelines detailing potential interactions with newer anti-epileptic drugs.
- 11.Perucca E, Hedges A, Makki KA, et al. A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in antiepileptic patients. Br J Pharmacol. 1984;11:533–9.Google Scholar
- 16.Levy RH, Bishop F, Streeter AJ. Explanation and prediction of drug interactions with topiramate using CYP450 inhibition spectrum. Epilepsia. 1995;36 Suppl 4:47–51.Google Scholar
- 18.Giuliano RA, Hiersemenzel E, Baltes G. Influence of a new antiepileptic drug (Levetiracetam, ucbLO59) on the pharmacokinetics and pharmacodynamics of oral contraceptives. Epilepsia. 1996;37 Suppl 4:90.Google Scholar
- 20.Bockbrader HN, Posvar EL, Hunt T. Pharmacokinetics of pregabalin and a concomitantly administered oral contraceptive shows no drug-drug interaction. Epilepsia. 2004;45 Suppl 3:153.Google Scholar
- 21.Bartoli A, Gatti G, Cipolla G, et al. A double-blind placebo-controlled study on the effect of vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oral contraceptives in healthy female volunteers. Epilepsia. 1997;38:702–7.PubMedCrossRefGoogle Scholar
- 22.Mengel HB, Houston A, Back DJ. An evaluation of the interaction between tiagabine and oral contraceptives in female volunteers. J Pharm Med. 1994;4:141–50.Google Scholar
- 24.Nakasa H, Nakamura H, Ono S, et al. Prediction of drug-drug interactions of zonisamide in humans from in vitro data. Eur J Clin Pharmacol. 1998; 54(2):177--83.Google Scholar
- 32.Marsh M, Kumar U. Practical recommendations for contraception. In: Panayiatopolis CP, Crawford PM, Thomson T, editors. Educational kit on epilepsies, vol 4, epilepsy and women. Oxford: Medicinae; 2008. p. 96–104.Google Scholar
- 33.•Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit. Clinical guidance: drug interactions with hormonal contraception. 2011. Available at: http://www.fsrh.org/pdfs/CEUGuidanceDrugInteractionsHormonal.pdf Accessed December 21, 2013. Hormonal contraceptive guidelines detailing potential interactions with anti-epileptic drugs.
- 34.Betts T, Crawford P. Women and epilepsy. London: Martin Dunitz; 1998.Google Scholar
- 36.Pharmacia Limited. Depo-Provera 150 mg/mL injection: Summary of Product Characteristics (SPC). 2007. Available at: http://www.medicines.org.uk/emc Accessed December 22, 2013.
- 40.HRA Pharma UK Ltd. ellaOne: Summary of Product Characteristics. 2010. Available at: http://www.medicines.org/emc Accessed December 21, 2013.