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. 2013 Oct;29(1):13-8.
doi: 10.1016/j.yebeh.2013.06.026. Epub 2013 Aug 2.

Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy

T L Reisinger  1 , M Newman, D W Loring, P B Pennell, K J Meador
Affiliations

Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy

T L Reisinger et al. Epilepsy Behav. 2013 Oct.

Abstract

The aims of the study were to characterize the magnitude of clearance changes during pregnancy for multiple antiepileptic drugs (AEDs) and to assess seizure frequency and factors increasing seizure risk in pregnant women with epilepsy. A retrospective analysis was performed for 115 pregnancies in 95 women with epilepsy followed at the Emory Epilepsy Center between 1999 and 2012. Antiepileptic drug blood levels (ABLs) obtained during routine clinical practice were used to calculate AED clearance at multiple points during pregnancy. Antiepileptic drug doses and seizure activity were also recorded. The data were analyzed for changes in clearance and dose across pregnancy and for an association between ABL and changes in seizure frequency. Significant changes in clearance during pregnancy were observed for lamotrigine (p<0.001) and levetiracetam (p<0.006). Average peak clearance increased by 191% for lamotrigine and 207% for levetiracetam from nonpregnant baseline. Marked variance was present across individual women and also across repeat pregnancies in individual women. Despite increased AED dose across most AEDs, seizures increased in 38.4% of patients during pregnancy. Seizure deterioration was significantly more likely in patients with seizures in the 12 months prior to conception (p<0.001) and those with localization-related epilepsy (p=0.005). When ABL fell >35% from preconception baseline, seizures worsened significantly during the second trimester when controlling for seizure occurrence in the year prior to conception. Substantial pharmacokinetic changes during pregnancy occur with multiple AEDs and may increase seizure risk. Monitoring of AED serum concentrations with dose adjustment is recommended in pregnant women with epilepsy. Further studies are needed for many AEDs.

Keywords: ABL; AED; AED blood level; Antiepileptic drugs; CBZ; Cl; Clearance; ESM; Epilepsy; LEV; LTG; OXC; PHT; Pharmacokinetics; Pregnancy; Seizure frequency; TPM; VPA; ZNS; antiepileptic drug; carbamazepine; clearance; ethosuximide; lamotrigine; levetiracetam; oxcarbazepine; phenytoin; topiramate; valproate; zonisamide.

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Conflict of interest statement

Conflicts of Interest

Dr. Meador reports receiving research support from the GlaxoSmithKline, EISAI Medical Research, Myriad Pharmaceuticals, Marinus Pharmaceuticals, NeuroPace, Pfizer, SAM Technology, Schwartz Biosciences, and UCB Pharma, the Epilepsy Foundation, and the NIH; received salary support to Emory University from the Epilepsy Consortium for research consultant work related for NeuroPace, Novartis, Upsher-Smith, and Vivus; served as a consultant for Eisai, GlaxoSmithKline, Johnson and Johnson (Ortho McNeil), Medtronics Spherics, and UCB Pharma, but the monies went to a charity of the company’s choice; received travel support from Sanofi Aventis; and also serves on the Professional Advisory Board for the Epilepsy Foundation and the editorial boards for Cognitive and Behavioral Neurology, Epilepsy and Behavior, Neurology, and Journal of Clinical Neurophysiology. Dr. Pennell has received grant support from NIH, CDC, Milken Family Foundation, UCB Pharma and Marinus Pharmaceuticals; and serves on the Professional Advisory Board for the Epilepsy Foundation, the Board of Directors for the American Epilepsy Society, and the editorial boards for Epilepsy Currents and Epilepsia. Dr. Loring reports receiving consulting fees from UCB, NeuroPace and Sanofi-Aventis and grant support from Myriad Pharm, Sam Technology, and Novartis. No other potential conflicts of interest are reported.

Figures

Figure 1
Figure 1
Percent change in monotherapy antiepileptic drug dosage each trimester of pregnancy. aOther AED monotherapy included topiramate (n=3), oxcarbazepine (n=2), valproate (n=1), zonisamide (n=1), and ethosuximide (n=1). Phenytoin was not included because no non-pregnant baseline dose was available. Dosage data for all individual AEDs and for polytherapy regimens is provided in Table e-2. LTG = lamotrigine; LEV = levetiracetam; CBZ = carbamazepine.
Figure 2
Figure 2
Percent patients with increased seizure frequency during pregnancy compared to the twelve months prior to conception. aOther monotherapy includes topiramate (n=3), oxcarbazepine (n=2), phenytoin (n=1), valproate (n=1), zonisamide (n=1), and ethosuximide (n=1). LTG = lamotrigine; LEV = levetiracetam; CBZ = carbamazepine.
See this image and copyright information in PMC

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