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Drugs, Supplies and Delivery
Sacubitril/Valsartan (Entresto)
Sacubitril/valsartan, marketed under the brand name Entresto, is a groundbreaking combination medication classified as an angiotensin receptor-neprilysin inhibitor (ARNI). It is primarily used for the treatment of heart failure with reduced ejection fraction (HFrEF) and has shown promise in managing hypertension. This article synthesizes information from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to provide a detailed overview of sacubitril/valsartan, including its mechanism, uses, dosing, side effects, precautions, and drug interactions.
Sacubitril/valsartan combines two active components:
- Sacubitril: A prodrug that inhibits neprilysin, an enzyme responsible for breaking down natriuretic peptides (e.g., ANP, BNP). By inhibiting neprilysin, sacubitril increases levels of these peptides, promoting vasodilation, natriuresis (sodium excretion), and diuresis.
- Valsartan: An angiotensin II receptor blocker (ARB) that prevents angiotensin II from binding to its receptors, reducing vasoconstriction, aldosterone secretion, and sodium/water retention (Lippincott, Lange).
Together, these mechanisms reduce blood pressure, improve cardiac function, and alleviate symptoms of heart failure (BNF).
- Heart Failure with Reduced Ejection Fraction (HFrEF):
- Indicated for patients with NYHA Class II-IV symptoms and reduced left ventricular ejection fraction (LVEF).
- Shown to reduce hospitalizations and improve survival compared to ACE inhibitors (BNF).
- Hypertension (Off-Label):
- Emerging evidence supports its use in resistant hypertension, particularly in patients with comorbid heart failure (Lippincott).
- Heart Failure:
- Initial dose: 49/51 mg twice daily (sacubitril/valsartan).
- Titrate to 97/103 mg twice daily after 2–4 weeks, as tolerated (BNF).
- Hypertension (Off-Label):
- Starting dose: 24/26 mg twice daily, titrated as needed (Lippincott).
Administration:
- Take with or without food.
- Avoid in patients currently taking ACE inhibitors (wait 36 hours after discontinuing ACE inhibitors before starting sacubitril/valsartan) (Lange).
- Common: Hypotension, hyperkalemia, dizziness, cough, and renal impairment (Lippincott).
- Serious: Angioedema (rare but potentially life-threatening), acute kidney injury, and severe hyperkalemia (BNF).
- Pregnancy: Contraindicated (Category D); risk of fetal harm, including renal dysfunction and developmental abnormalities (BNF).
- Renal Impairment: Use with caution in patients with severe renal dysfunction (eGFR <30 mL/min/1.73 m²). Monitor renal function regularly (Lippincott).
- Hyperkalemia: Monitor potassium levels, especially in patients with diabetes or renal impairment (Lange).
- ACE Inhibitors: Contraindicated concurrently due to increased risk of angioedema (BNF).
- ACE Inhibitors: Increased risk of angioedema; avoid concurrent use.
- Potassium-Sparing Diuretics/Potassium Supplements: Increased risk of hyperkalemia (Lippincott).
- NSAIDs: May reduce antihypertensive efficacy and worsen renal function (Lange).
- Lithium: Increased risk of lithium toxicity (BNF).
Sacubitril/valsartan is the generic name for this combination medication. It is marketed under the brand name Entresto®. As of now, generic versions are not widely available, but the medication is increasingly accessible due to its proven benefits in heart failure management.
