Entresto's Active Ingredients: Sacubitril and Valsartan
Entresto is classified as an angiotensin receptor-neprilysin inhibitor (ARNI), combining two mechanisms to combat heart failure. This dual action addresses hormonal pathways affecting blood vessel function and fluid balance.
Sacubitril: The Neprilysin Inhibitor
Sacubitril, converted to active metabolite LBQ657, inhibits neprilysin, an enzyme that breaks down beneficial natriuretic peptides. By blocking neprilysin, sacubitril increases these peptides' activity, promoting:
- Relaxed blood vessels: Encouraging vasodilation and lower blood pressure.
- Reduced fluid and sodium retention: Enhancing excretion through the kidneys.
Valsartan: The Angiotensin II Receptor Blocker
Valsartan is an angiotensin II receptor blocker (ARB). It blocks angiotensin II, a hormone causing blood vessel constriction and raising blood pressure. Valsartan complements sacubitril by:
- Causing Vasodilation: Further relaxing blood vessels.
- Reducing blood pressure: Contributing to a significant overall reduction in blood pressure.
The Synergy of the Combination
Sacubitril and valsartan create synergy. Sacubitril can increase angiotensin II, which is counteracted by valsartan blocking these harmful effects. This combined action enhances beneficial peptides and blocks harmful hormones, offering a more effective treatment for heart failure than either component alone.
Inactive Ingredients and Dosage Forms
Entresto also contains inactive ingredients for manufacturing. These vary between tablets and oral suspension pellets.
Some common inactive ingredients in Entresto tablets include:
- Colloidal silicon dioxide
- Crospovidone
- Low-substituted hydroxypropyl cellulose
- Magnesium stearate (of vegetable origin)
- Microcrystalline cellulose
- Talc
- Hypromellose (film coat)
- Polyethylene glycol 4000 (film coat)
- Titanium dioxide (film coat)
Different tablet strengths may contain iron oxides for color.
Understanding the Dual Action: A Comparison of Components
Below is a comparison highlighting the complementary roles of sacubitril and valsartan.
| Feature | Sacubitril (Neprilysin Inhibitor) | Valsartan (Angiotensin II Receptor Blocker - ARB) |
|---|---|---|
| Mechanism of Action | Blocks neprilysin, preserving beneficial peptides. | Blocks angiotensin II, preventing blood vessel constriction. |
| Cardiovascular Effect | Promotes vasodilation and reduces fluid/sodium. | Relaxes blood vessels and lowers blood pressure. |
| Effect on Hormones | Increases natriuretic peptides; may slightly increase angiotensin II. | Counteracts angiotensin II's effects. |
| Role in Entresto | Enhances natural protective neurohormonal systems. | Blocks harmful RAAS effects. |
Conclusion
Entresto combines sacubitril and valsartan to target different, interconnected pathways. Sacubitril increases beneficial peptides for vasodilation and fluid regulation, while valsartan blocks a hormone causing constriction. This dual mechanism effectively manages chronic heart failure, improving heart function, reducing symptoms, and lowering hospitalization risk.
Important Considerations for Use
Discuss potential side effects like low blood pressure, high potassium, and kidney issues with a healthcare provider. Entresto has a boxed warning against use in pregnancy due to fetal toxicity. A 36-hour washout period is needed when switching from an ACE inhibitor to reduce the risk of angioedema.
For more details, see the U.S. FDA prescribing information for Entresto.
