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

Side 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%)

Mode 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