Careful Lamotrigine Monitoring Needed in Pregnancy

Seizure worsening associated with ratio-to-target lamotrigine concentrations less than 65 percent

THURSDAY, Nov. 29 (HealthDay News) -- Pregnancy-related changes in drug metabolism lead to increased clearance of lamotrigine (Lamictal) and resultant lower drug levels, which means that pregnant women may experience seizure worsening if their drug levels are not carefully monitored, according to an article published online Nov. 28 in Neurology.

Page B. Pennell, M.D., of Emory University in Atlanta, and colleagues studied 53 women with epilepsy who were taking lamotrigine and subsequently became pregnant in order to characterize pregnancy-related changes in lamotrigine clearance and to assess the impact of therapeutic drug monitoring on seizure frequency. The researchers met with participants every one to three months, reviewing seizure diaries and conducting blood sampling.

Total and free lamotrigine clearance increased in all trimesters of pregnancy above non-pregnant baseline, with peak increases occurring in the third trimester. Free lamotrigine clearance was higher in white women than black women. A subset analysis of 36 women revealed that increased seizure frequency was associated with lower ratio-to-target concentration of lamotrigine, and a ratio less than 65 percent predicted seizure worsening. Women who did not adhere to a postpartum lamotrigine taper schedule were more likely to experience drug toxicity.

"This data-driven threshold index of a 65 percent ratio-to-target lamotrigine concentration should be used for introducing a dosage adjustment for women with epilepsy on lamotrigine during pregnancy," the authors conclude.

Pennell and colleagues disclose association with several pharmaceutical companies including GlaxoSmithKline and UCB Pharma.

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