Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy

P. Emanuela Voinescu, Suna Park, Li Q. Chen, Zachary N. Stowe, D. Jeffrey Newport, James C. Ritchie, Page B. Pennell

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To characterize the magnitude and time course of pregnancy-related clearance changes for different antiepileptic drugs (AEDs): levetiracetam, oxcarbazepine, topiramate, phenytoin, and valproate. A secondary aim was to determine if a decreased AED serum concentration was associated with increased seizure frequency.

METHODS: Women with epilepsy were enrolled preconception or early in pregnancy and prospectively followed throughout pregnancy and the first postpartum year with daily diaries of AED doses, adherence, and seizures. Study visits with AED concentration measurements occurred every 1-3 months. AED clearances in each trimester were compared to nonpregnant baseline using a mixed linear regression model, with adjustments for age, race, and hours postdose. In women on monotherapy, 2-sample t test was used to compare the ratio to target concentrations (RTC) between women with seizure worsening each trimester and those without.

RESULTS: AED clearances were calculated for levetiracetam (n = 18 pregnancies), oxcarbazepine (n = 4), topiramate (n = 10), valproate (n = 5), and phenytoin (n = 7). Mean maximal clearances were reached for (1) levetiracetam in first trimester (1.71-fold baseline clearance) (p = 0.0001), (2) oxcarbazepine in second trimester (1.63-fold) (p = 0.0001), and (3) topiramate in second trimester (1.39-fold) (p = 0.025). In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower RTC (p < 0.05).

CONCLUSION: AED clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate. Lower RTC was associated with seizure worsening. Early therapeutic drug monitoring and dose adjustment may be helpful to avoid increased seizure frequency.

Original languageEnglish (US)
Pages (from-to)e1228-e1236
JournalNeurology
Volume91
Issue number13
DOIs
StatePublished - Sep 25 2018

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etiracetam
Anticonvulsants
Epilepsy
Pregnancy
Seizures
Second Pregnancy Trimester
Valproic Acid
Phenytoin
First Pregnancy Trimester
Linear Models
Drug Monitoring
Postpartum Period
topiramate
oxcarbazepine
Serum

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Voinescu, P. E., Park, S., Chen, L. Q., Stowe, Z. N., Newport, D. J., Ritchie, J. C., & Pennell, P. B. (2018). Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology, 91(13), e1228-e1236. https://doi.org/10.1212/WNL.0000000000006240

Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. / Voinescu, P. Emanuela; Park, Suna; Chen, Li Q.; Stowe, Zachary N.; Newport, D. Jeffrey; Ritchie, James C.; Pennell, Page B.

In: Neurology, Vol. 91, No. 13, 25.09.2018, p. e1228-e1236.

Research output: Contribution to journalArticle

Voinescu, PE, Park, S, Chen, LQ, Stowe, ZN, Newport, DJ, Ritchie, JC & Pennell, PB 2018, 'Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy', Neurology, vol. 91, no. 13, pp. e1228-e1236. https://doi.org/10.1212/WNL.0000000000006240
Voinescu, P. Emanuela ; Park, Suna ; Chen, Li Q. ; Stowe, Zachary N. ; Newport, D. Jeffrey ; Ritchie, James C. ; Pennell, Page B. / Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. In: Neurology. 2018 ; Vol. 91, No. 13. pp. e1228-e1236.
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AU - Newport, D. Jeffrey

AU - Ritchie, James C.

AU - Pennell, Page B.

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