Levetiracetam use in pregnancy.
OBJECTIVE
To review data evaluating levetiracetam management of epilepsy during pregnancy.


METHODS
A literature search of PubMed (1966-June 2009) was performed using the terms pregnancy, epilepsy, levetiracetam, and anticonvulsants. Bibliographies of all articles retrieved were reviewed to identify additional relevant articles.


METHODS
All studies including humans and published in English with data describing levetiracetam management during pregnancy were included.


RESULTS
The pharmacokinetic studies included in this review demonstrate that the clearance of levetiracetam increases during pregnancy, particularly during the third trimester, which subsequently leads to decreased serum levetiracetam concentrations. The increase in clearance is most likely due to an increase in renal blood flow. The teratogenic studies included in this review included a total of 147 patients. Of these patients, 2% experienced a major congenital malformation (MCM) and 4.8% experienced a minor anomaly. All of the patients who had either an MCM or a minor anomaly were receiving antiepileptic drug (AED) polytherapy. It was unknown whether 10.9% of the 147 patients discussed were receiving levetiracetam monotherapy or AED polytherapy. None of the published literature assessed adherence to AED therapy. Folic acid supplementation was addressed in only one of the case series presented.


CONCLUSIONS
If levetiracetam is used during pregnancy, women should receive adequate amounts of folic acid (0.4-5 mg/day) and serum concentrations of levetiracetam should be determined before conception if possible and during each trimester, especially during the middle of the third trimester, to assess therapeutic concentrations. The dose may need to be increased during the third trimester to provide concentrations consistent with those before conception. Patients should be informed that there appears to be a small chance of malformations with levetiracetam, but that the data are limited.
Longo
Brian
B
St. Louis College of Pharmacy, St. Louis, MO 63110, USA.
Forinash
Alicia B
AB
Murphy
Julie A
JA
D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D000077287:Levetiracetam; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D014803:Vitamin B Complex / Q000627:therapeutic use
D000927:Anticonvulsants; D014803:Vitamin B Complex; D000077287:Levetiracetam; D005492:Folic Acid; D010889:Piracetam