Should Antiepileptic Serum Concentrations Be Monitored More Frequently in Pregnancy?

The average daily dose for patients in the first trimester was 600 mg for lamotrigine and 1976 mg for levetiracetam.
The average daily dose for patients in the first trimester was 600 mg for lamotrigine and 1976 mg for levetiracetam.

NEW ORLEANS — New data on the fluctuating pattern of serum drug concentrations for lamotrigine and levetiracetam throughout the pregnancies of women with epilepsy show the body begins to metabolize both drugs rapidly at week 16, indicating a need for more frequent testing of serum drug levels, according to research presented at the 72nd Annual Meeting of the American Epilepsy Society, held November 30 to December 4, 2018.

Researchers in this retrospective chart review of anti-seizure drug serum levels for pregnant women with epilepsy broke down serum data into trimester and 4-week time periods to analyze trends.

The data were obtained from patient visits to the University of Colorado Hospital Outpatient Epilepsy Clinics from January 2014 through March 2018. Over the period analyzed, 71 lamotrigine serum concentrations and 83 levetiracetam serum concentrations were collected.  

The average daily dose for patients in the first trimester was 600mg for lamotrigine and 1976mg for levetiracetam. Average daily lamotrigine doses increased to 632 mg and 944mg in the second and third trimesters, respectively. Average daily levetiracetam doses increased to 2298mg and 2933mg in the second and third trimesters, respectively.

Average daily doses for both drugs tended to substantially escalate at approximately 20 weeks of pregnancy due to drops in serum concentrations. There was an approximate 200mg jump between weeks 20 to 23 and weeks 24 to 27 for lamotrigine, followed by another approximate 200 mg jump in the next 4 weeks (weeks 28 to 31).

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Levetiracetam doses jumped approximately 500mg between weeks 16 to 19 and weeks 20 to 23, followed by another approximate 500mg jump in weeks 23 to 31.

Study investigators conclude that this pattern of data can allow clinicians to "act more proactively and start increasing the dose when the level is expected to start decreasing […] At pregnancy week 16 for both drugs it is prudent to get more frequent drug levels drawn as the female body starts to more rapidly metabolize these [anti-seizure drugs]. Based on this data levels should be obtained at least monthly if not every 2 weeks."

Limitations to the study include that serum levels for all patients were not always obtained at the same timepoints in pregnancy. Also, some patients may have used concomitant agents that can affect serum concentrations, the authors noted.

Reference

Makelky M, Bainbridge J, Shrestha A. Changes in lamotrigine and levetiracetam serum concentrations throughout individual weeks in pregnancy. Presented at: Annual Meeting of the American Epilepsy Society 2018; November 30-December 4, 2018; New Orleans, LA. Poster 3.230.