Sacubitril + Valsartan
Indications
Sacubitril + Valsartan is used for:
Heart Failure,
Adult Dose
Heart Failure
Indicated to reduce the risk of cardiovascular death and hospitalization for heart failure (HF) in patients with chronic heart failure (CHF) (NYHA class II-IV) and reduced ejection fraction
Recommended starting dose: 49 mg/51 mg PO BID
Target maintenance dose: After 2-4 weeks, double the dose to the target maintenance dose of 97 mg/103 mg PO BID as tolerated
Hepatic impairment
Mild (Child-Pugh A): No starting dose adjustment required
Moderate (Child-Pugh B): Reduce starting dose to 24 mg/26 mg BID; double the dose every 2-4 weeks to target maintenance dose of 97 mg/103 mg BID as tolerated
Severe (Child-Pugh C): Not recommended
Child Dose
Renal Dose
Renal impairment
Mild-to-moderate (eGFR ?30 mL/min/1.73 m²): No starting dose adjustment required
Severe (eGFR <30 mL/min/1.73 m²): Reduce starting dose to 24 mg/26 mg BID; double the dose every 2-4 weeks to target maintenance dose of 97 mg/103 mg BID as tolerated
Administration
May take with or without food
Contra Indications
Hypersensitivity to any component
History of angioedema related to previous ACE inhibitor or ARB therapy
Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan
Concomitant use with aliskiren in patients with diabetes
Precautions
Can cause fetal harm when administered to a pregnant woman; use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Black Box Warnings)
Observe for signs and symptoms of angioedema; if angioedema occurs, discontinue drug immediately, provide appropriate therapy, and monitor for airway compromise
Sacubitril/valsartan lowers blood pressure and may cause symptomatic hypotension; patients who are volume-depleted or salt-depleted, or those taking diuretics, are at greater risk
Monitor renal function and potassium levels in susceptible patients (eg, diabetes, hypoaldosteronism, high-potassium diet, renal artery stenosis); dosage reduction or interruption may be required
Pregnancy-Lactation
Pregnancy
Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, resulting oligohydramnios may cause fetal injury (eg, hypotension, neonatal skull hypoplasia, anuria, reversible and irreversible renal failure) and death
Neonates with a history of in utero exposure: Direct attention toward support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required
Lactation
Unknown if distributed in human breast milk; not recommended
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Interactions
Adverse Effects
Side effects of Sacubitril + Valsartan :
>10%
Hypotension (18%)
Hyperkalemia (12%)
1-10%
Cough (9%)
Dizziness (6%)
Orthostasis (2.1%)
Falls (1.9%)
<1%
Angioedema, all patients (0.5%); in black patients (2.4%)
Mechanism of Action
Combination is an angiotensin receptor-neprilysin inhibitor (ARNi)
Sacubitril: Neprilysin inhibitor; neprilysin is responsible for degradation of atrial and brain natriuretic peptide; the cardiovascular and renal effects of sacubitril’s active metabolite (LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic peptide); administration results in increased natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP
Valsartan: Angiotensin II receptor type I inhibitor; decreases blood pressure and blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II