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Women with epilepsy: 5 clinical pearls for contraception and preconception counseling

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2. Do not use lamotrigine with cyclic estrogen-progestin contraceptives.

Estrogens, but not progestins, are known to reduce the serum concentration of lamotrigine by about 50%.12,13 This is a clinically significant pharmacologic interaction. Consequently, when a cyclic estrogen-progestin contraceptive is prescribed to a woman taking lamotrigine, oscillation in lamotrigine serum concentration can occur. When the woman is taking estrogen-containing pills, lamotrigine levels decrease, which increases the risk of seizure. When the woman is not taking the estrogen-containing pills, lamotrigine levels increase, possibly causing such adverse effects as nausea and vomiting. If a woman taking lamotrigine insists on using an estrogen-progestin contraceptive, the medication should be prescribed in a continuous regimen and the neurologist alerted so that they can increase the dose of lamotrigine and intensify their monitoring of lamotrigine levels. Lamotrigine does not change the metabolism of ethinyl estradiol and has minimal impact on the metabolism of levonorgestrel.4

3. Estrogen-progestin contraceptives require valproate dosage adjustment.

A few studies report that estrogen-progestin contraceptives accelerate the metabolism of valproate and reduce circulating valproate concentration,14,15 as noted in Table 2.In one study, estrogen-progestin contraceptive was associated with 18% and 29% decreases in total and unbound valproate concentrations, respectively.14 Valproate may induce polycystic ovary syndrome in women.16 Therefore, it is common that valproate and an estrogen-progestin contraceptive are co-prescribed. In these situations, the neurologist should be alerted prior to prescribing an estrogen-progestin contraceptive to WWE taking valproate so that dosage adjustment may occur, if indicated. Valproate does not appear to change the metabolism of ethinyl estradiol or levonorgestrel.5

4. Preconception counseling: Before conception consider using an AED with low teratogenicity.

Valproate is a potent teratogen, and consideration should be given to discontinuing valproate prior to conception. In a study of 1,788 pregnancies exposed to valproate, the risk of a major congenital malformation was 10% for valproate monotherapy, 11.3% for valproate combined with lamotrigine, and 11.7% for valproate combined with another AED, but not lamotrigine.17 At a valproate dose of 1,500 mg daily, the risk of major malformation was 24% for valproate monotherapy, 31% for valproate plus lamotrigine, and 19% for valproate plus another AED, but not lamotrigine.17 Valproate is reported to be associated with the following major congenital malformations: spina bifida, ventricular and atrial septal defects, pulmonary valve atresia, hypoplastic left heart syndrome, cleft palate, anorectal atresia, and hypospadias.18

In a study of 7,555 pregnancies in women using a single AED, the risk of major congenital anomalies varied greatly among the AEDs, including: valproate (10.3%), phenobarbital (6.5%), phenytoin (6.4%), carbamazepine (5.5%), topiramate (3.9%), oxcarbazepine (3.0%), lamotrigine (2.9%), and levetiracetam (2.8%).19 For WWE considering pregnancy, many experts recommend use of lamotrigine, levetiracetam, or oxcarbazepine to minimize the risk of fetal anomalies.

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