Sacubitril/Valsartan

DEA Class; Rx

Common Brand Names; Entresto

• Angiotensin Receptor-Neprilysin Inhibitors (ARNi); 
• ARBs; 
• Neprilysin Inhibitors

Oral combination product containing a neprilysin inhibitor (sacubitril) and an angiotensin II receptor blocker (valsartan)
Used for heart failure; usually administered in conjunction with other heart failure therapies in place of an ACE inhibitor or other ARB in adult patients
Allow a 36 hour washout period between administration of ACE inhibitor and sacubitril; valsartan

Indicated to reduce risk of cardiovascular death and hospitalization in chronic heart failure (CHF); benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal

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

Hypotension (18%)

Hyperkalemia (12%)

Cough (9%)

Dizziness (6%)

Orthostasis (2.1%)

Falls (1.9%)

Angioedema, all patients (0.5%); in black patients (2.4%)

Hypersensitivity (rash, pruritus, anaphylaxis)

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)

Not for use in patients with hereditary angioedema; 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

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

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