Is it safe for a postpartum woman with a history of epilepsy or bipolar disorder to continue taking lamotrigine (75 mg twice daily (BID)) while breastfeeding?

Lamotrigine 75 mg BID During Breastfeeding

Lamotrigine 75 mg twice daily is safe to continue while breastfeeding, with close monitoring of the infant for potential adverse effects recommended during the first month postpartum.

Safety Profile and Evidence Base

Lamotrigine is considered a safe antiepileptic drug for breastfeeding women, with rare and usually mild adverse effects in exposed infants 1. The medication does transfer into breast milk at measurable concentrations, but the benefits of both breastfeeding and continued maternal treatment outweigh the minimal risks 2.

Breast Milk Transfer and Infant Exposure

• The mean milk-to-plasma ratio for lamotrigine is approximately 41.3%, with significant individual variability 3
• Infant plasma concentrations reach approximately 18.3% of maternal plasma levels 3
• The theoretical infant dose is 0.51 mg/kg per day, representing a relative infant dose of 9.2% of the maternal weight-adjusted dose 3
• This excretion rate is comparable to other antiepileptic drugs considered safe during breastfeeding 3, 4

Clinical Outcomes in Breastfed Infants

A retrospective study of 20 mother-infant pairs taking lamotrigine (mean dose 161.1 mg/day, range 50-400 mg/day) demonstrated reassuring safety data 5:

• No infants showed neonatal withdrawal syndrome scores of 2 or higher up to 1 month after delivery 5
• Observed adverse events (drowsiness, skin rash, jaundice, heart murmur, poor suckling, retractive breathing) were not serious and infants recovered 5
• There were no significant differences in adverse events compared to control groups 5
• 19 of 20 pairs successfully continued breastfeeding until 1 month postpartum 5

Monitoring Recommendations

Close periodic monitoring of breastfed infants is essential to minimize the probability of severe side effects 1:

• Monitor for drowsiness, skin rash, poor feeding, and respiratory symptoms during the first month 5
• Mild thrombocytosis has been observed in some infants but without clinical significance 3
• Infant serum drug concentration monitoring is advisable but not compulsory 4

Clinical Decision Algorithm

Continue lamotrigine at the current dose (75 mg BID) while breastfeeding because:

1. The dose of 150 mg/day total falls within the low-to-moderate range demonstrated to be relatively safe 5
2. Discontinuing effective seizure or mood disorder treatment poses greater risks to the mother-infant dyad than the minimal infant exposure 1
3. Aiming for the lowest effective maternal plasma levels is beneficial, as higher maternal concentrations lead to higher breast milk concentrations 2

Important Caveats

• Traditional anticonvulsants like carbamazepine, valproic acid, and phenytoin are generally considered safe during breastfeeding, providing context that lamotrigine's safety profile is comparable 4
• The benefits of breastfeeding (health, nutritional, immunological, developmental, social, economic, and environmental) should not be overlooked despite detectable infant exposure 2, 4
• Therapeutic drug monitoring (TDM) in this population can help optimize maternal dosing to achieve the lowest effective plasma levels 2