Can I split an Entresto (sacubitril/valsartan) 49/51 tablet in half?

Splitting Entresto (Sacubitril/Valsartan) 49/51 mg Tablets

Entresto (sacubitril/valsartan) 49/51 mg tablets should not be split in half due to potential issues with dose accuracy and medication stability.

Rationale for Not Splitting Entresto Tablets

Formulation Considerations

• Entresto is a fixed-dose combination tablet containing two active ingredients (sacubitril and valsartan) in precise amounts
• The tablet is designed to deliver the exact doses of both medications simultaneously
• Splitting could result in uneven distribution of the active ingredients

Dosing Options in Guidelines

According to clinical guidelines, Entresto is available in specific dosage strengths that should be used as prescribed:

• The American College of Cardiology/American Heart Association guidelines specify that Entresto comes in three dosage strengths 1:

  • 24/26 mg (sacubitril/valsartan)
  • 49/51 mg (sacubitril/valsartan)
  • 97/103 mg (sacubitril/valsartan)

• The European Society of Cardiology also recognizes these specific dosage forms without mentioning tablet splitting 1

Proper Dose Titration

If a lower dose is needed, the appropriate approach is to:

1. Use the commercially available lower strength tablet (24/26 mg)
2. Follow the established titration schedule:
   • Start with 24/26 mg twice daily if needed
   • Titrate to 49/51 mg twice daily
   • Target dose is 97/103 mg twice daily as tolerated

Clinical Implications of Improper Dosing

Efficacy Concerns

• Suboptimal dosing may lead to reduced clinical benefits in heart failure management
• The PARADIGM-HF trial demonstrated mortality and morbidity benefits at specific doses 2

Safety Concerns

• Improper dosing could increase risk of adverse effects:
  • Hypotension
  • Renal dysfunction
  • Hyperkalemia
  • Potential drug interactions 3

Alternative Approaches

If the current dose is not tolerated:

1. Consult with the prescribing physician about switching to the commercially available lower dose (24/26 mg)
2. Consider temporary dose reduction rather than tablet splitting
3. Evaluate for factors contributing to intolerance (volume depletion, concurrent medications)

Monitoring Recommendations

For patients requiring dose adjustments:

• Monitor blood pressure closely
• Check renal function and electrolytes within 1-2 weeks of dose changes
• Assess for symptoms of hypotension or other adverse effects

Conclusion

For patients who need a lower dose than 49/51 mg, the appropriate approach is to use the commercially available 24/26 mg tablet rather than splitting the higher-dose tablet. This ensures accurate dosing of both active ingredients and maintains the medication's intended efficacy and safety profile.