Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications

Torbjörn Tomson, Cecilie Johannessen Landmark, Dina Battino

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Summary Pregnancy is a state where pharmacokinetic changes are more pronounced and more rapid than during any other period of life. The consequences of such changes can be far reaching, not least in the management of epilepsy where the risks with uncontrolled seizures during pregnancy need to be balanced against potential teratogenic effects of antiepileptic drugs (AEDs). This article aims to review the literature on gestational effects on the pharmacokinetics of older and newer generation AEDs and discuss the implications for the treatment of epilepsy in women during pregnancy. Pregnancy can affect the pharmacokinetics of AEDs at any level from absorption, distribution, metabolism, to elimination. The effect varies depending on the type of AED. The most pronounced decline in serum concentrations is seen for AEDs that are eliminated by glucuronidation (UGT), in particular lamotrigine where the effect may be profound. Serum concentrations of AEDs that are cleared mainly through the kidneys, for example, levetiracetam, can also decline significantly. Some AEDs, such as carbamazepine seem to be affected only marginally by pregnancy. Data on pharmacokinetics during pregnancy are lacking completely for some of the newer generation AEDs: pregabalin, lacosamide, retigabine, and eslicarbazepine acetate. Where data are available, the effects of pregnancy on serum concentrations seem to vary considerably individually and are thus difficult to predict. Although large-scale systematic studies of the clinical relevance of the pharmacokinetic alterations are lacking, prospective and retrospective case series have reported an association between declining serum concentrations and deterioration in seizures control. The usefulness of routine monitoring of AED serum concentrations in pregnancy and of dose adjustments based on falling levels, are discussed in this review. We suggest that monitoring could be important, in particular when women have been titrated to the lowest effective AED dose and serum concentration before pregnancy, and when that individual optimal concentration can be used as reference.

Original languageEnglish
Pages (from-to)405-414
Number of pages10
JournalEpilepsia
Volume54
Issue number3
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Anticonvulsants
Pregnancy
Pharmaceutical Preparations
Pharmacokinetics
Serum
Therapeutics
etiracetam
Epilepsy
Seizures
Accidental Falls
Carbamazepine
Risk Management
Kidney

Keywords

  • Antiepileptic drugs
  • Epilepsy
  • Pharmacokinetics
  • Pregnancy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Antiepileptic drug treatment in pregnancy : Changes in drug disposition and their clinical implications. / Tomson, Torbjörn; Landmark, Cecilie Johannessen; Battino, Dina.

In: Epilepsia, Vol. 54, No. 3, 03.2013, p. 405-414.

Research output: Contribution to journalArticle

Tomson, Torbjörn ; Landmark, Cecilie Johannessen ; Battino, Dina. / Antiepileptic drug treatment in pregnancy : Changes in drug disposition and their clinical implications. In: Epilepsia. 2013 ; Vol. 54, No. 3. pp. 405-414.
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