“Late” Withdrawal Syndrome after Carbamazepine In Utero Exposure in a CYP2C9 Slow Metabolizer Newborn

• Main Authors: Caroline F. Samer, Evangelia Passia, Nathalie Rock, Riccardo E. Pfister, Kuntheavy R. Ing Lorenzini, Jules Desmeules
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-04-01
• Series: Frontiers in Pharmacology
• Subjects: carbamazepine; drug withdrawal; pharmacogenetics; cytochrome P450; epilepsy
• Online Access: http://journal.frontiersin.org/article/10.3389/fphar.2017.00217/full
• ISSN: 1663-9812

We report a case of carbamazepine withdrawal syndrome following in utero exposure to carbamazepine related to a pharmacogenetic predisposition factor. The infant was born at 37 1/7 weeks’ gestation by cesarean section to a mother treated for epilepsy with carbamazepine. One hour and thirty minutes after birth, the infant presented a respiratory distress with severe oxygen desaturation requiring intubation 5 h after birth. On the third day of life the infant developed clinical signs of a withdrawal syndrome which resolved progressively after 16 days and symptomatic treatment. The infant genotype analysis showed two low activity CYP2C9 allelic variants (∗2/∗3 heterozygote) predicting a CYP2C9 slow metabolizer phenotype which could explain reduced carbamazepine elimination and a late and long-lasting withdrawal symptoms observed 3 days after birth. The association of a withdrawal syndrome with carbamazepine exposure has not been previously reported and pharmacogenetic tests might therefore be useful in identifying patients at risk.