Is Nefopam (acetamide derivative) safe to use during breastfeeding?

Nefopam Use During Breastfeeding

Nefopam should be used with caution during breastfeeding as it passes into breast milk, though infant exposure is likely to be minimal at less than 3% of the maternal dose on a body weight basis. 1

Safety Profile and Evidence

The safety of nefopam during breastfeeding has limited but specific evidence:

• A study examining nefopam excretion in human milk found that while the drug appears in breast milk at concentrations equivalent to plasma (milk:plasma ratio 1.2 ± 0.7), the infant exposure would be less than 0.05 mg/kg/day, which represents less than 3% of the maternal dose on a body weight basis 1

• A more recent randomized trial specifically investigating nefopam's effect on lactation after cesarean section found that:

  • Nefopam did not delay the onset of lactation compared to paracetamol
  • Neurobehavioral scores of infants were comparable between nefopam and paracetamol groups
  • However, infants in the nefopam group required significantly more supplemental artificial milk on days 2-3 2

• The FDA drug label for nefopam includes a general caution to consult a healthcare professional before use during breastfeeding, but does not specifically contraindicate its use 3

Clinical Decision Algorithm

1. First-line alternatives: Consider using analgesics with established safety profiles in breastfeeding:

   • Paracetamol (acetaminophen) - extremely safe with minimal transfer to breast milk 4, 5
   • NSAIDs (ibuprofen, diclofenac, naproxen) - considered safe with low levels in breast milk 4, 5
   • Morphine - recommended as opioid of choice when strong analgesia is required 4

2. If nefopam is clinically indicated:

   • Use the lowest effective dose for the shortest duration possible
   • Time administration immediately after breastfeeding to maximize clearance time before next feeding
   • Monitor the infant for unusual drowsiness, poor feeding, or other adverse effects
   • Consider supplemental feeding if needed, as suggested by the finding of increased artificial milk requirements in the nefopam study 2

Special Considerations

• Infant age matters: Neonates and young infants (<6 weeks) have immature hepatic metabolism and require extra caution with any medication exposure through breast milk 6

• Risk-benefit assessment: The benefits of adequate pain control for the breastfeeding mother should be weighed against the potential minimal risks to the infant 4, 7

• Pharmacological properties: Nefopam has anticholinergic and dopaminergic effects that theoretically could affect lactation, though the clinical trial evidence suggests this is not a significant concern 2

Monitoring Recommendations

If nefopam is used during breastfeeding:

• Observe the infant for signs of unusual drowsiness, poor feeding, or irritability
• Monitor maternal milk production
• Consider temporary pumping and discarding milk during peak drug concentration periods if there are concerns about infant exposure

While nefopam appears to have minimal impact on lactation and infant neurobehavior based on limited evidence, safer alternatives with more established safety profiles should be considered first when managing pain in breastfeeding women.