Anticonvulsants in pregnancy

Abstract

Objective: To review the potential problems and their management associated with the use of anticonvulsant drugs during pregnancy.

Data sources: Studies published between 1968 and 1990 assessing the effect of pregnancy on the pharmacokinetics of anticonvulsant drugs, the teratogenicity of anticonvulsants, breast feeding and anticonvulsants and use of the oral contraceptive pill in patients taking anticonvulsant medication, were reviewed.

Results of data synthesis: In general, plasma levels fall during pregnancy and rise during the puerperium. A number of factors including possible reduced absorption, increased volume of distribution, reduced protein binding, increased clearance and noncompliance, contribute to this fall in plasma concentration. All anticonvulsants are potentially teratogenic. The incidence of fetal malformations is higher in patients treated with multiple anticonvulsant drugs and on higher dosages with higher plasma levels. Anticonvulsants are excreted in low concentrations in breast milk. All anticonvulsants except valproic acid have been associated with failure of the oral contraceptive pill. This is due to liver enzyme induction of these drugs.

Conclusion: As plasma levels of anticonvulsants fall during pregnancy, concentrations should be monitored regularly. Due to the fall in protein binding, marginally low total plasma levels of highly protein bound drugs may not reflect reduced unbound levels, and hence an increase in dosage may not be required. In order to reduce teratogenicity, one should aim to use a single anticonvulsant drug and the lowest dosage able to achieve seizure control. In general, breast feeding is not contraindicated.

PIP: The objective of this study was to review the potential problems and their management associated with the use of anticonvulsants in pregnancy. Studies published between 1968-90 assessing the effect of pregnancy on the pharmacokinetics of anticonvulsant drugs, the teratogenicity of anticonvulsants, breastfeeding, and anticonvulsants and the use of oral contraceptives (OCs) in patients taking anticonvulsant medication were reviewed. In general, plasma levels fall during pregnancy and rise during the puerperium. A number of factors including possible reduced absorption, increased volume of distribution, reduced protein binding, increased clearance, and noncompliance all contribute to this fall in plasma concentration. All such drugs are potentially teratogenic. The incidence of fetal malformations is higher in those patients treated with multiple anticonvulsant drugs and on higher dosages with higher plasma levels. Anticonvulsants are excreted i low concentrations in breastmilk. All except valproic acid have been associated with the failure of OCs, this due to liver enzyme induction of these drugs. As plasma levels of anticonvulsants fall during pregnancy, concentrations should be monitored regularly. Due to the fall in protein binding, marginally low total plasma levels of highly protein bound drugs may not reflect reduced unbound levels, and thus an increase in dosage may not be required. In order to reduce teratogenicity, one should aim to use a single anticonvulsant drug and the lowest dosage able to receive seizure control. In general, breastfeeding is not contraindicated.