¡¡ NEW YORK (Reuters Health) - In pregnant women treated with lamotrigine to prevent seizures, lamotrigine clearance increases by more than 90% by the third trimester. To prevent emergent seizure activity, investigators recommend therapeutic drug monitoring with dose adjustment when women with epilepsy become pregnant.
"Ideally, therapeutic drug monitoring would be managed by a neurologist working closely with an obstetrician," lead investigator Dr. Page B. Pennell told Reuters Health. Dose adjustments are made to maintain the patient's target concentration, "which is based on many factors including epilepsy syndrome, seizure types, history of responsiveness and of side effects with lamotrigine, and hormonal contraceptive use."
"If possible, the target concentration should be determined prior to conception," she continued. If that's not an option, "the lamotrigine concentration obtained earliest in pregnancy could be used as the target, especially if seizures have not yet worsened."
In their prospective study, the research team at Emory University in Atlanta, Georgia, evaluated 305 blood samples from 53 pregnancies. They report their findings in the online edition of Neurology, published on November 28.
Total lamotrigine clearance was significantly increased in all trimesters, with an average peak increase of 94% in the third trimester above the nonpregnant baseline.
According to Dr. Pennell, "If the lamotrigine concentration during pregnancy fell below 65% of the target concentration, the risk for seizure worsening increased."
Records showed that 33% of patients had a decrease in seizures, 28% experienced no change, and 39% had increased seizure activity, which represented "improved seizure control compared with previous reports of lamotrigine use during pregnancy."
Clearance rates returned to baseline within the first postnatal month. To prevent toxicity, the clinicians recommend a drug taper over 10 days, "with return to preconception dose or preconception dose plus 50 mg to help counteract the effects of sleep deprivation."
"Our study of 52 live births demonstrated newborn outcomes similar to the general population, and no association to dose of any adverse outcomes," Dr. Pennell noted.
Nevertheless, she advocates further study with much larger patient populations to ensure the safety of the regimen. "This would best be studied either through a pregnancy registry or a multicenter study with assessment of long-term neurodevelopmental outcomes."
Neurology 2007.
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