"In animal studies, levetiracetam produced evidence of developmental toxicity at doses similar to or greater than human therapeutic doses.

Administration to female rats throughout pregnancy and lactation was associated with increased incidences of minor fetal skeletal abnormalities and retarded offspring growth pre- and/or postnatally at doses >/=350 mg/kg/day (approximately equivalent to the maximum recommended human dose of 3000 mg [MRHD] on a mg/m ² basis) and with increased pup mortality and offspring behavioral alterations at a dose of 1800 mg/kg/day (6 times the MRHD on a mg/m ² basis). The developmental no effect dose was 70 mg/kg/day (0.2 times the MRHD on a mg/m ² basis). There was no overt maternal toxicity at the doses used in this study.

When pregnant rats were treated during the period of organogenesis, fetal weights were decreased and the incidence of fetal skeletal variations was increased at a dose of 3600 mg/kg/day (12 times the MRHD). 1200 mg/kg/day (4 times the MRHD) was a developmental no effect dose. There was no evidence of maternal toxicity in this study. Treatment of rats during the last third of gestation and throughout lactation produced no adverse developmental or maternal effects at doses of up to 1800 mg/kg/day (6 times the MRHD on a mg/m ² basis)[1].

Treatment of pregnant rabbits during the period of organogenesis resulted in increased embryofetal mortality and increased incidences of minor fetal skeletal abnormalities at doses >/=600 mg/kg/day (approximately 4 times MRHD on a mg/m ² basis) and in decreased fetal weights and increased incidences of fetal malformations at a dose of 1800 mg/kg/day (12 times the MRHD on a mg/m ² basis). The developmental no effect dose was 200 mg/kg/day (1.3 times the MRHD on a mg/m ² basis). Maternal toxicity was also observed at 1800 mg/kg/day.

Long described three infants whose mothers had been treated throughout all three trimesters with levetiracetam (750 to 3000 mg daily) monotherapy. The  infants were delivered uneventfully and showed no evidence of birth defects or cognitive alterations at 6 months postpartum[2].

There are no adequate and well-controlled studies in pregnant women. Keppra ^® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus  [1].

Pregnancy Exposure Registry   To facilitate monitoring fetal outcomes of pregnant women exposed to Keppra ^® , physicians should encourage patients to register, before fetal outcome is known (e.g., ultrasound, results of amniocentesis, etc.), in the Antiepileptic Drug Pregnancy Registry by calling (888) 233-2334 (toll free).

BREAST FEEDING:  A milk:maternal plasma ratio of 3.09 was reported in one woman receiving  levetiracetam [3]. The manufacturer states that because of the potential for serious adverse reactions in nursing infants from Keppra ^® , a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. [1]

SEARCH LITERATURE

1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2004: 3230-3232
2. Long L. Levetiracetam monotherapy during pregnancy: a case series.Epilepsy Behav. 2003;4:447-8. MEDLINE
3. Kramer G et al. Levetiracetam accumulation in breast milk. Epilepsia 2002;43(suppl7):105

Created: 4/5/2004
Updated: 4/5/2004