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(Abst. 3.230), 2018

Changes in Lamotrigine and Levetiracetam Serum Concentrations Throughout Individual Weeks in Pregnancy
Authors: Matthew Makelky, University of Colorado; Jacquelyn Bainbridge, University of Colorado; and Archana Shrestha, University of Colorado
Content: Rationale: Pharmacologic management of epilepsy in women with epilepsy (WWE) presents unique challenges during pregnancy. Significant physiological changes during pregnancy may affect pharmacokinetics of anti-seizure drugs (ASDs) given to pregnant patients, resulting in fluctuations in serum drug concentrations. There is no clear guidance on how to best adjust individual drugs during pregnancy.  Methods: Serum anti-seizure drug levels are closely monitored at the University of Colorado Hospital Outpatient Epilepsy Clinics during each visit to the PPEC clinic. A retrospective chart review of serum ASD level data was done between January 1st2014 to March 31stof 2018. Serum levels correlating to the week of pregnancy based on the estimated date of delivery based on the woman’s last known menstrual cycle were recorded in a designated spreadsheet. The data was then broken down by trimester and then into four-week periods of time to analyze trends in data. Results: We collected 71 serum concentrations of lamotrigine, and 83 for levetiracetam over the period analyzed. The average daily dose (ADD) in the first trimester for lamotrigine was 600mg, with second trimester yielding an ADD of 632 mg, and the third showing 944 mg. For Levetiracetam the ADD for the first trimester was 1976 mg, the second showed 2298mg, and the third revealed 2933 mg. For both drugs at approximately 20 weeks the doses began to escalate substantially due to lower serum levels being attained.  Specifically there was approximately 200 mg jump in average dosing from weeks 20-23 to weeks 24-27 in lamotrigine, which then increased by approximately 200 mg more in the following four weeks (28-31). For levetiracetam average doses increased by approximately 500 mg from weeks 16-19 to 20-23, and another 500 mg change between weeks 23 to 31.  Conclusions: With this pattern of data the treatment team can act more proactively and start increasing the dose when the level is expected to start decreasing. This is in contrast to the current model of reactively waiting for an appointment and levels to be done, which can delay decisions and potentially put women at greater risk for seizures. 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 ASDs. Based on this data levels should be obtained at least monthly if not every 2 weeks. This close monitoring will lead to more timely and accurate dose changes.  Funding: No funding was received.