Is lisinopril (angiotensin-converting enzyme inhibitor) safe during breastfeeding?

Lisinopril Safety During Breastfeeding

Lisinopril should generally be avoided during breastfeeding, particularly during the infant's first month of life, due to concerns about potential neonatal hypotension, although the actual risk appears to be low based on minimal transfer into breast milk. 1, 2, 3

Evidence on Lisinopril in Breastfeeding

FDA Labeling and Official Guidance

• The FDA drug label for lisinopril states that it is unknown whether lisinopril is excreted in human milk, and recommends that a decision should be made whether to discontinue nursing or discontinue lisinopril, taking into account the importance of the drug to the mother 2
• Lisinopril is classified as FDA Pregnancy Category D, indicating evidence of human fetal risk, though this classification primarily applies to pregnancy rather than breastfeeding 4

Recent Research Findings

• A recent quantitative analysis found extremely minimal transfer of lisinopril into breast milk, with a relative infant dose of only 0.06% (more than 100 times lower than the standard 10% safety threshold) 3
• The mean milk concentration was reported as 0.49 ng/mL per 10 mg daily dose, suggesting very low infant exposure 3

Guideline Recommendations

• According to the American Heart Association, ACE inhibitors are generally not recommended for women who are breastfeeding infants, particularly during the infant's first month of life, due to concerns about potential neonatal hypotension 1
• However, the same guideline acknowledges that several ACE inhibitors (captopril, enalapril, benazepril, and quinapril) have very low levels in breast milk, making significant levels in a breastfed infant unlikely 1
• Lisinopril was not specifically mentioned among the ACE inhibitors with documented low breast milk levels 1

Risk-Benefit Assessment

Factors to Consider:

1. Maternal need for medication:

   • The importance of treating maternal hypertension or heart failure must be weighed against potential risks to the infant
   • Untreated maternal cardiovascular disease carries its own risks 5, 6

2. Infant age and health status:

   • Younger infants (especially <1 month) may be more vulnerable to potential adverse effects 1
   • Premature infants or those with renal impairment may be at higher risk

3. Alternative medications:

   • Consider whether other antihypertensives with better-established safety profiles during lactation could be used instead

Clinical Recommendations

For Most Breastfeeding Women:

• If possible, consider switching to alternative antihypertensives with better-established safety during breastfeeding
• If lisinopril must be used:
  • Monitor the infant for signs of hypotension, poor feeding, or lethargy
  • Consider timing medication administration just after breastfeeding or before the infant's longest sleep period 5
  • The extremely low transfer into breast milk (0.06% relative infant dose) suggests minimal risk to healthy, term infants 3

Special Considerations:

• For neonates (<1 month): Greater caution is warranted; consider alternative medications if possible
• For premature infants or those with renal impairment: Avoid lisinopril if possible due to potentially increased sensitivity

Common Pitfalls to Avoid

• Unnecessarily discontinuing breastfeeding when medication is needed by the mother
• Failing to consider the risks of untreated maternal hypertension or heart failure
• Not consulting reliable, up-to-date resources about medication safety during lactation 5, 7, 8
• Assuming all ACE inhibitors have identical safety profiles in breastfeeding 4

While the most recent research suggests minimal infant exposure through breast milk, the general recommendation remains cautious, especially for younger infants. The decision should balance maternal need for treatment against potential risks, with consideration of alternative medications when appropriate.