take from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
Tricyclic antidepressants: Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold.
Trifluoperazine: The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added.
Trimipramine: Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold.
PREGNANCY AND LACTATION
Pregnancy
Levetiracetam is classified as FDA pregnancy risk category C. In animal studies, there was evidence that levetiracetam produced developmental toxicity at doses similar to or greater than human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. Levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The effect of levetiracetam on labor and delivery in humans is not known. NOTE: Maternal clearance of levetiracetam is higher during pregnancy compared to baseline, especially during the third trimester (see Pharmacokinetics); if levetiracetam is continued during pregnancy, monitor seizure frequency closely. A dosage adjustment may be necessary for some patients. Physicians are advised to recommend that pregnant patients receiving levetiracetam enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to provide information about the effects of in utero exposure to the drug. Patients must call 1-888-233-2334 to enroll in the registry. The manufacturer of Keppra, UCB, has also established a pregnancy registry that patients or healthcare providers can enroll in by calling 1-888-537-7734.
Levetiracetam is excreted in human breast milk. According to the manufacturer, because of the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue breast-feeding or discontinue levetiracetam. Other experts suggest that breast-feeding may be continued during levetiracetam therapy in some cases. In one small case series, foremilk samples were taken 3—5 days postpartum from 7 women who were taking levetiracetam 1,500—3,500 mg/day PO. The mean milk:maternal serum concentration ratio was 1 (range 0.76—1.33); however, six of the infant corresponding serum concentrations were very low or below the level of quantification. The remaining infant did not have a serum concentration measured at 3—5 days of age. Milk concentrations were measured again from one or more women at 2 weeks, 4 weeks, 6—8 weeks, 4 months, and 10 months postpartum, and the maternal milk:serum ratios were similar to those at 3—5 days postpartum. No infant-related adverse effects were noted. In another case series including 11 mother-infant pairs, levetiracetam was excreted into breast milk at a concentration similar to that in maternal plasma; the mean milk:plasma ratio was 1.05 (range 0.78—1.55). Assuming a daily milk intake of 150 ml/kg/day, the infant dose was estimated to be approximately 2.4 mg/kg/day. Although no safe dosage range has been established in the neonatal |
