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Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications
Author(s) -
Tomson Torbjörn,
Landmark Cecilie Johannessen,
Battino Dina
Publication year - 2013
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12109
Subject(s) - medicine , lamotrigine , pregnancy , pharmacokinetics , carbamazepine , levetiracetam , oxcarbazepine , phenytoin , lacosamide , pharmacology , epilepsy , glucuronidation , drug , therapeutic drug monitoring , pediatrics , psychiatry , biochemistry , chemistry , genetics , biology , enzyme , microsome
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 ( AED s). This article aims to review the literature on gestational effects on the pharmacokinetics of older and newer generation AED s and discuss the implications for the treatment of epilepsy in women during pregnancy. Pregnancy can affect the pharmacokinetics of AED s 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 AED s that are eliminated by glucuronidation ( UGT ), in particular lamotrigine where the effect may be profound. Serum concentrations of AED s that are cleared mainly through the kidneys, for example, levetiracetam, can also decline significantly. Some AED s, 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 AED s: 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.