Can Entresto (sacubitril/valsartan) cause nipple pain?

Entresto (Sacubitril/Valsartan) and Nipple Pain

There is no established association between Entresto (sacubitril/valsartan) and nipple pain in the current medical literature or guidelines. While Entresto has documented side effects, nipple pain is not among the reported adverse effects in cardiovascular guidelines or drug information.

Known Side Effects of Entresto

• Symptomatic hypotension is the most commonly reported side effect of sacubitril/valsartan, occurring more frequently than with other heart failure medications 1
• Other documented side effects include:
  • Potential for hyperkalemia (though less than with spironolactone) 1
  • Risk of angioedema (though incidence is low) 2
  • Possible drug interactions with statins (sacubitril can inhibit OATP1B1, OATP1B3, OAT1, and OAT3 transporters) 1, 3

Differential Diagnosis for Nipple Pain

When a patient on Entresto reports nipple pain, consider these more likely causes:

• Cyclical mastalgia (accounts for up to 70% of breast pain cases) - typically hormonal in origin and associated with menstrual cycles 1
• Noncyclical breast pain (accounts for up to 25% of breast pain cases) - often inflammatory in nature, unilateral and more focal 1
• Medication-induced breast pain from other sources:
  • Hormonal medications (hormone replacement therapy, oral contraceptives) 1
  • Selective serotonin reuptake inhibitors 1
• Mastitis or breast abscess (may present initially as focal pain) 1
• Extramammary causes (referred pain from musculoskeletal, cardiac, pulmonary, or gastrointestinal conditions) 1

Clinical Approach for Patients on Entresto with Nipple Pain

1. Evaluate for more common causes of nipple/breast pain as listed above 1
2. Review the complete medication list for other potential causes of breast pain 1
3. Consider the timing of pain onset in relation to Entresto initiation
4. If no other cause is identified and symptoms began after starting Entresto:
   • Continue Entresto if the pain is mild and heart failure management is optimal 1, 2
   • Consider reporting the case as a potential adverse drug reaction for further investigation

Monitoring Recommendations

• For patients on Entresto, routine monitoring should focus on:
  • Blood pressure (due to risk of hypotension) 1
  • Renal function 1
  • Serum potassium levels 1
• If nipple pain occurs and Entresto is continued, document the symptoms and monitor for changes in severity or associated findings 1

Key Considerations

• The benefits of Entresto in heart failure with reduced ejection fraction are well-established, with significant reductions in cardiovascular mortality and hospitalizations 2, 4
• When evaluating any potential medication side effect, the risk-benefit ratio should be carefully considered before discontinuation 2, 4
• Unexplained breast pain in any patient warrants appropriate evaluation to rule out underlying breast disease, regardless of medication use 1