ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart
failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients
with left ventricular ejection fraction (LVEF) below normal.
LVEF is a variable measure, so use clinical judgment in deciding whom to treat.
IMPORTANT SAFETY INFORMATION
WARNING: FETAL TOXICITY
When pregnancy is detected, discontinue ENTRESTO as soon as possible
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus
ENTRESTO is contraindicated in patients with hypersensitivity to any component. ENTRESTO is
contraindicated in patients with a history of angioedema related to previous angiotensin-converting
enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy.
ENTRESTO is contraindicated with concomitant use of ACE inhibitors. Do not administer within
36 hours of switching from or to an ACE inhibitor. ENTRESTO is contraindicated with concomitant
use of aliskiren in patients with diabetes.
Angioedema: ENTRESTO may cause angioedema. Angioedema associated with laryngeal edema may be fatal.
ENTRESTO has been associated with a higher rate of angioedema in Black patients and in patients with
a prior history of angioedema. ENTRESTO should not be used in patients with hereditary angioedema.
If angioedema occurs, discontinue ENTRESTO immediately, provide appropriate therapy, and monitor for
airway compromise. ENTRESTO must not be re-administered.
Hypotension: ENTRESTO lowers blood pressure and may cause
symptomatic hypotension. Patients with an activated renin-angiotensin system, such as volume- and/or
salt-depleted patients (e.g., those being treated with high doses of diuretics), are at greater risk.
Correct volume or salt depletion prior to administration of ENTRESTO or start at a lower dose.
If hypotension persists despite dose adjustment of diuretics, concomitant antihypertensive drugs, and
treatment of other causes of hypotension (e.g., hypovolemia), reduce the dosage or temporarily
discontinue ENTRESTO. Permanent discontinuation of therapy is usually not required.
Impaired Renal Function: Decreases in renal function may be
anticipated in susceptible individuals treated with ENTRESTO. In patients whose renal function depends
upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive
heart failure), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated
with oliguria, progressive azotemia and, rarely, acute renal failure and death. Closely monitor serum
creatinine, and down-titrate or interrupt ENTRESTO in patients who develop a clinically significant
decrease in renal function.
ENTRESTO may increase blood urea and serum creatinine levels in patients with bilateral or unilateral
renal artery stenosis. In patients with renal artery stenosis, monitor renal function. Avoid use with
aliskiren in patients with renal impairment (eGFR <60 mL/min/1.73 m2).
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised
renal function, concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors,
with ENTRESTO may result in worsening of renal function, including possible acute renal failure.
These effects are usually reversible. Monitor renal function periodically.
Hyperkalemia: Hyperkalemia may occur with ENTRESTO. Monitor
serum potassium periodically and treat appropriately, especially in patients with risk factors for
hyperkalemia such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet.
Dosage reduction or interruption of ENTRESTO may be required.
Concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements,
or salt substitutes containing potassium, may lead to increases in serum potassium.
ARBs: Avoid use of ENTRESTO with an ARB, because ENTRESTO contains
the angiotensin II receptor blocker valsartan.
Lithium: Increases in serum lithium concentrations and lithium
toxicity have been reported during concomitant administration of lithium with angiotensin II receptor
antagonists. Monitor serum lithium levels during concomitant use with ENTRESTO.
Common Adverse Events: In a clinical trial of patients with heart failure with reduced ejection fraction,
the most commonly observed adverse events with ENTRESTO vs enalapril, occurring at a frequency of at least 5% in either group, were hypotension
(18%, 12%), hyperkalemia (12%, 14%), cough (9%, 13%), dizziness (6%, 5%), and renal failure/acute renal failure (5%, 5%).
No new adverse reactions were identified in a trial of the remaining indicated population.
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