Sacubitril + Valsartan
Generic Details
Generic Name
Sacubitril-valsartan
Other Names
- Entresto
Drug Class
- Angiotensin Receptor Neprilysin Inhibitor (ARNI)
Chemical Formula
C24H29N5O3.C24H29NO4
Molecular Weight
692.8 g/mol (sacubitril) + 447.5 g/mol (valsartan)
Mechanism of Action
- Sacubitril inhibits neprilysin, an enzyme that breaks down beneficial peptides, while valsartan is an angiotensin II receptor blocker (ARB) which blocks the vasoconstrictor effects of angiotensin II.
Indications
- Heart failure (reduced ejection fraction)
Common Dosage Forms
- Tablet
Typical Dosage
- The recommended starting dose is sacubitril/valsartan 49/51 mg twice daily, which can be titrated up to the target maintenance dose of 97/103 mg twice daily.
Pediatric Dosage
- Safety and efficacy have not been established in pediatric patients.
Geriatric Dosage
- Dose adjustment may be necessary due to age-related decrease in renal function.
Side Effects
- Hypotension
- Hyperkalemia
- Cough
- Dizziness
- Renal impairment
Contraindications
- History of angioedema with ACE inhibitors or ARBs
- Use with aliskiren in patients with diabetes
Pregnancy Category
- D
Lactation Safety
- Not recommended
Drug Interactions
- Potassium-sparing diuretics
- NSAIDs
- Lithium
Overdose Symptoms
- Hypotension
- Bradycardia
- Hyperkalemia
Antidote for Overdose
- Intravenous fluids, vasopressors, hemodialysis
Storage Conditions
- Store at 20-25°C (68-77°F)
Pharmacokinetics
- Absorption: Rapid and almost complete absorption
- Distribution: Highly protein-bound
- Metabolism: Hepatic (sacubitril) and hepatic (valsartan)
- Excretion: Primarily renal
Precautions
- Monitor renal function and potassium levels regularly
Warnings
- Risk of angioedema
- Hypotension
- Renal impairment
- Hyperkalemia
Others
- It is important to discontinue ACE inhibitors or ARBs at least 36 hours before starting sacubitril/valsartan to reduce the risk of angioedema.