Can Entresto Be Split or Broken in Half?
No, Entresto (sacubitril/valsartan) tablets should not be broken, crushed, or split—they must be swallowed whole. This is critical because the medication is formulated as a specific supramolecular complex that requires intact delivery for proper absorption and efficacy 1.
Why Entresto Cannot Be Split
- Formulation integrity: Entresto is a supramolecular sodium salt complex combining sacubitril (a neprilysin inhibitor prodrug) and valsartan (an ARB) in precise ratios that must remain intact 1
- Absorption requirements: The medication is absorbed primarily in the stomach and proximal small bowel, and altering the tablet structure could compromise bioavailability 2
- Dosing precision: The drug requires twice-daily administration at specific doses (24/26 mg, 49/51 mg, or 97/103 mg) that have been validated in clinical trials 3
Available Dosing Options
If a lower dose is needed, use the commercially available lower-strength tablets rather than splitting higher-strength tablets 3:
- Starting dose: 49/51 mg twice daily (or 24/26 mg twice daily in certain patients)
- Target dose: 97/103 mg twice daily
- Titration: Increase every 2-4 weeks as tolerated 3
Clinical Considerations
- Dose adjustments: If blood pressure, renal function, or tolerability issues arise, switch to a lower commercially available strength rather than splitting tablets 2, 4
- Uptitration challenges: Only 27% of patients achieve target dose within 6 months in real-world practice, often due to side effects or slower titration—this should be managed by using appropriate tablet strengths, not by splitting 4
- Monitoring: Check blood pressure, heart rate, renal function, and potassium 1-2 weeks after initiation or dose changes 2, 5
Common Pitfall to Avoid
Do not attempt to "customize" doses by splitting tablets—this practice undermines the medication's pharmacokinetic profile and may result in subtherapeutic dosing or unpredictable absorption 2, 1.