Enalapril is the angiotensin converting enzyme (ACE) inhibitor of choice during breastfeeding. Recommendations apply to full term and healthy infants only.
Enalapril is the preferred angiotensin converting enzyme (ACE) inhibitor during breastfeeding as published evidence is available about its excretion into breast milk, it has been used therapeutically in infants, and it has the most favourable pharmacokinetics.
However, most ACE inhibitors can be used during breastfeeding if clinically appropriate.
Evidence
Limited evidence shows milk levels of ACE inhibitors are low. Most ACE inhibitors are also metabolised to their active metabolite which is poorly absorbed orally. Therefore, any active metabolite in breast milk is also unlikely to be absorbed significantly by the infant via breast milk.
Indications
Recommendations apply to any indication the medicine is being used for, such as hypertension, heart failure or post-myocardial infarction.
Choice of antihypertensive
Choice of anti-hypertensive in breastfeeding will be dependent on a number of factors, including patient-specific characteristics, clinical condition and patient preference.
Drugs from different pharmacological classes may need to be used in combination and therefore their additive suitability in breastfeeding will need to be considered.
Treatment choice should primarily be directed at controlling symptoms, with safety in breastfeeding a secondary consideration.
Neonates and infants less than 2 months are at the most risk from the side-effects of ACE inhibitors, particularly hypotension, because they have underdeveloped clearance capacities, which means they can’t metabolise the medicines as effectively.
In addition, there is theoretical concern that ACE inhibitors could affect kidney development. However, this has not been proven or reported in any infants exposed to ACE inhibitors via breast milk.
If an ACE inhibitor is the best therapeutic option to treat the maternal condition, extra caution should be taken when breastfeeding younger infants and neonates.
Specific recommendations
Preferred choice
Enalapril is the preferred choice due to negligible levels in breast milk, favourable drug properties and use therapeutically in infants.
Infant monitoring
As a precaution, monitor the infant for hypotension which may manifest as drowsiness, lethargy, pallor, poor feeding and inadequate weight gain.
In younger infants, monitor for normal urine production (wet nappies).
Further information
Enalapril is a pro-drug which is metabolised to the active metabolite enalaprilat. Enalaprilat has a long half-life, potentially causing an increased risk of accumulation in the infant, but it is poorly absorbed orally and therefore would not reach the infant’s serum in significant levels.
Limited evidence shows that enalapril and enalaprilat pass into breast milk in negligible amounts (0.07–0.56% of the weight-adjusted maternal enalapril dose) with maternal single doses up to 20mg. Similar breast milk levels were reported in a mother taking enalapril 10mg daily for 11 months. Infant serum levels were not measured.
No infant side-effects have been reported from exposure via milk.
Although, not licensed for use in children, enalapril has been used therapeutically in infants from birth.
Use with caution
Lisinopril can be used with caution during breastfeeding, but enalapril is preferred.
Infant monitoring
As a precaution, monitor the infant for hypotension which may manifest as drowsiness, lethargy, pallor, poor feeding and inadequate weight gain.
In younger infants, monitor for normal urine production (wet nappies).
Further information
Unlike most other ACE inhibitors, lisinopril is the active compound.
There is no information on excretion of lisinopril in breast milk. As with other ACE inhibitors, and based on its drug properties, it would be expected to be excreted into breast milk in small amounts.
No infant side-effects have been reported.
Use with caution
Perindopril can be used with caution during breastfeeding, but enalapril is preferred.
Infant monitoring
As a precaution, monitor the infant for hypotension which may manifest as drowsiness, lethargy, pallor, poor feeding and inadequate weight gain and pallor.
In younger infants, monitor for normal urine production (wet nappies).
Further information
Perindopril is a pro-drug which is metabolised to the active metabolite perindoprilat. Perindopril has a very long half life (30 hours for perindopril and 120 hours for perindoprilat), which increases the risk of drug accumulation in the infant and side-effects. However, this has not been demonstrated in published information to date.
Limited published evidence shows that perindopril and perindoprilat pass into milk in very small amounts. (0.0005 – 4.6% of the weight-adjusted maternal dose), with maternal doses of 4–20mg daily. Infant plasma levels were very low.
No infant side-effects have been reported from exposure via milk. In one study, normal infant growth and development was described.
Use with caution
Ramipril can be used with caution during breastfeeding, but enalapril is preferred.
Infant monitoring
As a precaution, monitor the infant for hypotension which may manifest as drowsiness, lethargy, pallor, poor feeding and inadequate weight gain. In younger infants, monitor for normal urine production (wet nappies).
Further information
Ramipril is a pro-drug which is metabolised to the active metabolite ramiprilat. Limited unpublished information suggests that levels of ramipril and ramiprilat were undetectable in milk after a single dose of 10mg.
As with other ACE inhibitors, and based on its drug properties, it would be expected to be excreted into breast milk in small amounts.
There is no information on infant serum levels.
No infant side-effects have been reported from exposure via milk.
the ACE inhibitor in question is not included in our advice
you need further advice.
About our recommendations
Recommendations are based on published evidence where available. However, evidence is generally very poor and limited, and can require professional interpretation. Assessments are often based on reviewing case reports which can be conflicting and lack detail.
If there is no published clinical evidence, assessments are based on: pharmacodynamic and pharmacokinetic principles, extrapolation from similar drugs, risk assessment of normal clinical use, expert advice, and unpublished data.
Simulated data are now increasingly being used due to the ethical difficulties around gathering good quality evidence in this area.