Is sacubitril-valsartan (Entresto), dapagliflozin (Forxiga), and eplerenone (Inspra) safe during breastfeeding?

Safety of Sacubitril-Valsartan, Dapagliflozin, and Eplerenone During Breastfeeding

These medications should generally be avoided during breastfeeding due to insufficient safety data, with the notable exception that recent evidence suggests sacubitril-valsartan transfers into breast milk at negligible levels and may be considered in select cases where maternal heart failure requires treatment.

Sacubitril-Valsartan (Entresto)

Recent Evidence Shows Minimal Transfer

• A 2024 study demonstrated that sacubitril-valsartan transfer into human milk is minimal, with valsartan levels below detection limits (0.19 ng/mL) in all milk samples from five breastfeeding mothers 1
• Sacubitril peaked at 1 hour post-dose with a mean concentration of 1.52 ng/mL, yielding a relative infant dose (RID) of only 0.01% 1
• The active metabolite LBQ657 peaked at 4 hours with an average concentration of 9.5 ng/mL and RID of 0.22% 1
• The combined RID of <0.25% is far below the industry safety threshold of <10%, suggesting minimal risk to breastfed infants 1
• Two mothers in this study continued breastfeeding while taking sacubitril-valsartan without observing negative effects in their infants 1

Traditional Guideline Concerns About Valsartan Component

• The European Society of Cardiology guidelines classify valsartan (the ARB component) with unknown transfer to breast milk and list it as FDA Category D during pregnancy due to serious fetal risks including renal dysplasia, oligohydramnios, and growth retardation 2
• Angiotensin II receptor blockers and aldosterone antagonists should be avoided during pregnancy and breastfeeding according to ESC guidelines 2

Clinical Decision-Making

• For mothers with peripartum cardiomyopathy or heart failure requiring sacubitril-valsartan, the 2024 data supports that breastfeeding may be compatible given the negligible drug transfer 1
• This represents a shift from traditional manufacturer recommendations against breastfeeding, which were based on theoretical concerns rather than actual data 1

Dapagliflozin (Forxiga)

Lack of Safety Data

• No specific evidence was provided regarding dapagliflozin transfer into breast milk
• As a newer SGLT2 inhibitor approved in 2014, there is insufficient published data on its safety during lactation 3
• Given the lack of safety data and the availability of alternative diabetes and heart failure treatments with established safety profiles, dapagliflozin should be avoided during breastfeeding 3, 4

General Principles for Newer Medications

• Newer agents require caution during breastfeeding because they have not been adequately studied in lactation 3
• When prescribing for breastfeeding patients, medications with the lowest risk to the infant should be selected 3

Eplerenone (Inspra)

Aldosterone Antagonist Concerns

• The ESC guidelines state that aldosterone antagonists should be avoided during pregnancy and breastfeeding 2
• No specific data on eplerenone transfer into breast milk was provided in the evidence
• Eplerenone should be avoided during breastfeeding due to lack of safety data and guideline recommendations against aldosterone antagonist use 2

Class Effect Considerations

• As an aldosterone antagonist in the same class as spironolactone, theoretical concerns exist about hormonal effects on the infant
• The general principle is that drugs not studied in lactation should be used with extreme caution or avoided 4

Alternative Approaches for Heart Failure During Breastfeeding

Safer Medication Options

• If heart failure management is needed during breastfeeding, consider medications with established safety profiles rather than these newer agents 3
• Consultation with the infant's pediatrician is encouraged when maternal medications are necessary 5
• Reliable resources such as LactMed (a free government-sponsored database) should be consulted for current safety information 3

Key Clinical Principles

Risk-Benefit Assessment

• The decision to use these medications must weigh the mother's need for effective heart failure treatment against potential infant exposure 5, 3
• In emergency or life-threatening maternal conditions, drugs may need to be used even without complete breastfeeding safety data 2
• The benefits of breastfeeding are numerous and well-established, so cessation should not be recommended without strong evidence of harm 5, 6, 3

Timing Strategies if Medications Are Used

• If these medications must be continued, advise the mother to take them just after breastfeeding or before the infant's longest sleep period to minimize infant exposure 5
• Consider monitoring for any adverse effects in the breastfed infant if maternal medication use continues 5

Common Pitfalls to Avoid

• Do not automatically advise discontinuation of breastfeeding based solely on manufacturer labeling, which is often overly cautious due to lack of data rather than evidence of harm 5, 4
• Avoid using outdated resources; consult current databases like LactMed for the most recent information 3
• Do not fail to consider that most medications transfer into breast milk at levels far below those that would affect the infant 6, 3
• Remember that lack of information does not equal evidence of harm, though caution is still warranted 4