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Severe Apnea in an Infant Exposed to Lamotrigine in Breast Milk

Adviser, RELIS Nord-Norge (Regional Medicines Information Center of North Norway), University Hospital of North Norway Trust, Tromsø, Norway

Lena Aronsen, MD

Chief Physician, Clinical Pharmacologist, Department of Laboratory Medicine, Division of Diagnostic Services, University Hospital of North Norway Trust

Kristin Wasland, MD

Resident Peadiatrics, Peadiatric Ward, NLSH Bodø, Norway

Lars Småbrekke, MSc Pharm MPH PhD

Researcher, Institute of Pharmacy, University of Tromsø, Norway

Solveig Vorren, MSc Pharm

Adviser, RELIS Nord-Norge (Regional Medicines Information Center of North Norway), University Hospital of North Norway Trust

Reprints: Elisabet Nordmo, RELIS Nord-Norge, University Hospital of North Norway Trust, Box 79, N-9038 Tromsø, Norway, fax +47 77 64 58 94, elisabet.nordahl.nordmo{at}unn.no

OBJECTIVE: To report a case of severe apnea in an infant exposed to lamotrigine through breast-feeding.

CASE SUMMARY: A 16-day-old infant developed several mild episodes of apnea that culminated in a severe cyanotic episode requiring resuscitation. A thorough examination at the hospital gave no evidence of underlying diseases that could explain the reaction. The mother had used lamotrigine in increasing doses throughout pregnancy, and at the time of the apneic episodes, she used 850 mg/day. The infant was fully breast-fed, and the neonatal lamotrigine serum concentration was 4.87 µg/mL at the time of admission. Breast-feeding was terminated, and the infant fully recovered.

DISCUSSION: Although there are several reports on extensive passage of lamotrigine into breast milk, this is the first published report of a serious adverse reaction in a breast-fed infant. Lamotrigine clearance increases throughout pregnancy, and maternal dose increases are often necessary to maintain therapeutic effect. After delivery, clearance rapidly returns to preconception levels, enhancing the risk of adverse reactions in both mothers and breast-fed infants if the dose is not sufficiently reduced. In this case, the dose was slowly reduced after delivery, and the maternal lamotrigine serum concentration more than doubled in the week before the neonatal apneic episodes. A high lamotrigine concentration was detected in the breast milk, and the neonatal lamotrigine serum concentration was in the upper therapeutic range. The neonatal lamotrigine elimination half-life was approximately twice that seen in adults. The Naranjo probability scale indicated a probable relationship between apnea and exposure to lamotrigine through breast-feeding in this infant.

CONCLUSIONS: Infants can be exposed to clinically relevant doses of lamotrigine through breast-feeding. Individual risk/benefit assessment is important, and close monitoring of both mother and child is advisable, especially during the first 3 weeks postpartum.

Key Words: adverse effects, breast-feeding, breast milk, lamotrigine, pregnancy

Published Online, October 13, 2009. www.theannals.com, DOI 10.1345/aph.1M254