An interaction between antiepileptic drugs (AEDs) and the combined oral contraceptive pill was first proposed when the dose of estradiol in the oral contraceptive pill was reduced from 100 to 50μg. There was a higher incidence of breakthrough bleeding and contraceptive failure among women with epilepsy compared with women in general.
Since then, interaction studies have been undertaken to look for possible interactions between AEDs and the combined oral contraceptive pill. Phenobarbital (phenobarbitone), phenytoin, carbamazepine, oxcarbazepine, felbamate and topiramate have been shown to increase the metabolism of ethinylestradiol and progestogens. Therefore, if a women is on one of the AEDs and wishes to take the oral contraceptive pill, she will need to take a preparation containing at least 50μg of ethinylestradiol. Levonorgestrel implants are contraindicated in women receiving these AEDs because of cases of contraceptive failure. It is recommended that medroxyprogesterone injections be given every 10 rather than 12 weeks to women who are receiving AEDs that induce hepatic microsomal enzymes.
There are no interactions between the combined oral contraceptive pill, progesterone-only pill, medroxyprogesterone injections or levonorgestrel implants and the AEDs valproic acid (sodium valproate), vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam, zonisamide, ethosuximide and the benzodiazepines. Therefore, normal dose contraceptive preparations can be used in patients receiving these AEDs.
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No funding was used in the preparation of this manuscript. The author has undertaken studies for and had sponsorship from GlaxoSmithKline, JanssenCilag, Novartis, Sanofi-Synthelabo, UCB, Parke-Davis and Elan Pharmaceuticals.
Coulam CB, Annegers JF. Do anticonvulsants reduce the efficacy of oral contraceptives? Epilepsia 1979; 20: 519–26PubMedCrossRefGoogle Scholar
Back DJ, Grimmer SFM, Orme ML, et al. Evaluation of Committee on Safety of Medicine yellow card reports on oral contraceptive interactions. Br J Pharmacokinet Pharmacol 1988; 13: 527–32Google Scholar
Park BK, Breckenridge AM. Clinical implications of enzyme induction and enzyme inhibition. Clin Pharmacokinet 1981; 6: 1–24PubMedCrossRefGoogle Scholar
Backström T, Sodergärd R. The influence of antiepileptic drugs on steroid plasma levels and binding during the menstrual cycle [abstract]. Acta Endocrinol Suppl (Copenh) 1977; Suppl. 212: 42Google Scholar
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: 533–9Google Scholar
Tomson T, Svensson J, Hilton-Brown P. Relationship of inter-individual dose to plasma concentration of carbamazepine: indication of dose-dependent induction of metabolism. Ther Drug Monit 1989; 11:533–9PubMedCrossRefGoogle Scholar
Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate likelihood of metabolic pharmacodynamic interactions. Clin Pharmacokinet 1997; 32: 210–58PubMedCrossRefGoogle Scholar
Wright SA, Stevens JC. The human hepatic cytochromes 450 involved in drug metabolism. Crit Rev Toxicol 1992; 22: 1–21CrossRefGoogle Scholar
D’Arcy PF. Drug interactions with oral contraceptives. Drug Intell Clin Pharm 1986; 20: 353–62PubMedGoogle Scholar
Back DJ, Orme MLE. Pharmacokinetic drug interactions with oral contraceptives. Clin Pharmacokinet 1990; 18: 472–84PubMedCrossRefGoogle Scholar
Wilkinson GR. Clearance approaches in pharmacology. Pharmacol Rev 1987; 39: 1–47PubMedGoogle Scholar
Back DJ, Bates M, Bowden A, et al. The interactions of phenobarbital and other anticonvulsants with oral contraceptive therapy. Contraception 1980; 22: 495–503PubMedCrossRefGoogle Scholar
Sonnen AEH. Sodium valproate and the pill. In: Akimoto H, Kazamatsun H, Seino M, et al., editors. Advances in epileptology. Proceedings of the 13th Epilepsy International Symposium. New York: Raven Press, 1982: 429–32Google Scholar
Crawford P, Chadwick DJ, Martin C, et al. The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids. Br J Clin Pharmacol 1990; 30: 892–6PubMedCrossRefGoogle Scholar
Crawford PM, Chadwick D, Cleland P, et al. The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptives. Contraception 1986; 33: 23–9PubMedCrossRefGoogle Scholar
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; 36: 702–7CrossRefGoogle Scholar
Saano V, Banield CR, Reidenberg P, et al. Effects of felbamate on the pharmacokinetics of low-dose combination oral contraceptive. Clin Pharmacol Ther 1995; 58: 523–31PubMedCrossRefGoogle Scholar
Holdich T, Whiteman P, Orme M, et al. Effect of lamotrigine on the pharmacology of the combined oral contraceptive pill. Epilepsia 1991; 32Suppl. 1: 96Google Scholar
Eldon MA, Underwood BA, Randinitis EJ, et al. Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol. Neurology 1998; 50: 1146–8PubMedCrossRefGoogle Scholar
Rosenfeld WE, Doose DR, Walker SA, et al. Effects of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 1997; 38: 317–23PubMedCrossRefGoogle Scholar
Mengel HB, Houston A, Back DJ. An evaluation of the interaction between tiagabine and oral contraceptives in female volunteers. J Pharm Med 1994; 4: 141–50Google Scholar
Klosterkov JP, Saano V, Haring P, et al. Possible interaction between oxcarbazepine and an oral contraceptive. Epilepsia 1992; 33: 1149–52CrossRefGoogle Scholar
Fattore C, Cipolla G, Gatti G, et al. Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Epilepsia 1999; 40: 783–7PubMedCrossRefGoogle Scholar
Giuliano RA, Hiersemenzel E, Baltes G, et al. Influence of a new antiepileptic drug (Levetiracetam, ucbLO59) on the pharmacokinetics and pharmacodynamics of oral contraceptives [abstract]. Epilepsia 1996; 37Suppl. 4: 90Google Scholar
Orme M, Crawford P, Chadwick D, et al. af]Contraception, epilepsy and pharmacokinetics. In: Trimble MR, editor. Women and epilepsy. Chichester: J. Wiley & Sons, 1991: 145–58Google Scholar
Geurts TBP, Goorissen EM, Sitsen JME. Summary of drug interactions with oral contraceptives. Carnforth, Lancs: Parthenon Publishing Group, 1993: 57Google Scholar
Gilbert JC, Scott AC, Galloway DB, et al. Ethosuximide liver enzyme induction and D-glucaric acid excretion. Br J Clin Pharmacol 1974; 1: 249–52PubMedCrossRefGoogle Scholar
Kurt H. Interactions between anticonvulsants and other commonly prescribed drugs. Epilepsia 1984; 25: S118–31CrossRefGoogle Scholar
Frisium. ABPI: Compendium of data sheets. Summary of product characteristics. 1999–2000. London: Datapharm Publications Ltd., 1999: 568–9Google Scholar
Mehta DK, editor. British National Formulary — BNF40, September 2000. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2000Google Scholar
Schumacher RC, Fantel C, Kelton E, et al. Evaluation of elimination of 14C-felbamate in healthy men [abstract]. Epilepsia 1990; 31Suppl. 1: 21–2Google Scholar
Wilbur K, Ensom MHH. Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants. Clin Pharmacokinet 2000; 38: 355–65PubMedCrossRefGoogle Scholar
Levy RH, Bishop F, Streeter AJ, et al. Explanation and prediction of drug interactions with topiramate using CYP450 inhibition spectrum. Epilepsia 1995; 36Suppl. 4: 47–51Google Scholar
Nicolas JM, Collart P, Gerin B, et al. In vitro evaluation of potential drug interactions with levetiracetam, a new antiepileptic agent. Drug Metab Dispos 1999; 27: 250–4PubMedGoogle Scholar
Nakasa H, Komiya M, Ohmori S, et al. Characterisation of human liver microsomal cytochrome P-450 responsible for reductive metabolism of zonisamide. Drug Metab Dispos 1993; 21: 777–81PubMedGoogle Scholar
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; 52(2): 177–83CrossRefGoogle Scholar
Betts T, Crawford P. Women and epilepsy. London: Martin Dunitz, 1998Google Scholar
Krauss GL, Brandt J, Campbell M, et al. Antiepileptic medication and oral contraceptive interactions: a national survey of neurologists and obstetricians. Neurology 1996; 46: 1534–9PubMedCrossRefGoogle Scholar
Haukkamaa M. Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant therapy. Contraception 1986; 33: 559–65PubMedCrossRefGoogle Scholar
Crawford P, Lee P. Gender difference in the management of epilepsy — what women are hearing. Seizure 1999; 8: 135–9PubMedCrossRefGoogle Scholar
Trussell J, Kost K. Aguide to interpreting contraceptive efficacy studies. Obstet Gynacol 1990; 76: 558–67Google Scholar