HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
ENTRESTO safely and effectively. See full prescribing information for
ENTRESTO.
ENTRESTO
®
(sacubitril and valsartan) tablets, for oral use
ENTRESTO
®
SPRINKLE (sacubitril and valsartan) oral pellets
Initial U.S. Approval: 2015
WARNING: FETAL TOXICITY
See full prescribing information for complete boxed warning.
• When pregnancy is detected, discontinue ENTRESTO as soon as
possible. (5.1)
• Drugs that act directly on the renin-angiotensin system can cause
injury and death to the developing fetus. (5.1)
----------------------------RECENT MAJOR CHANGES--------------------------
Dosage and Administration (2.3, 2.5) 4/2024
----------------------------INDICATIONS AND USAGE---------------------------
ENTRESTO is a combination of sacubitril, a neprilisin inhibitor, and
valsartan, an angiotensin II receptor blocker, and 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. (1.1)
• for the treatment of symptomatic heart failure with systemic left ventricular
systolic dysfunction in pediatric patients aged one year and older.
ENTRESTO reduces NT-proBNP and is expected to improve
cardiovascular outcomes. (1.2)
-----------------------DOSAGE AND ADMINISTRATION-----------------------
• The recommended starting dosage for adults is 49 mg/51 mg orally twice
daily. The target maintenance dose is 97 mg/103mg orally twice daily.
(2.2)
• Adjust adult doses every 2 to 4 weeks to the target maintenance dose, as
tolerated by the patient. (2.2)
• For pediatric patients, see the Full Prescribing Information for
recommended dosage, titrations, preparation and administration
instructions. (2.3, 2.4, 2.5)
• Reduce starting dose to half the usually recommended starting dosage for:
patients not currently taking an angiotensin-converting enzyme (ACE)
inhibitor or angiotensin II receptor blocker (ARB) or previously taking a
low dose of these agents. (2.6)
patients with severe renal impairment. (2.7)
patients with moderate hepatic impairment. (2.8)
----------------------DOSAGE FORMS AND STRENGTHS---------------------
• Film-coated tablets: 24/26 mg; 49/51 mg; 97/103 mg (3)
• Film-coated oral pellets within capsules: 6 mg/6 mg; 15 mg/16 mg (3)
--------------------------------CONTRAINDICATIONS-----------------------------
• Hypersensitivity to any component. (4)
• History of angioedema related to previous ACEi or ARB therapy. (4)
• Concomitant use with ACE inhibitors. (4, 7.1)
• Concomitant use with aliskiren in patients with diabetes. (4, 7.1)
------------------------WARNINGS AND PRECAUTIONS-----------------------
• Observe for signs and symptoms of angioedema and hypotension. (5.2, 5.3)
• Monitor renal function and potassium in susceptible patients. (5.4, 5.5)
-------------------------------ADVERSE REACTIONS------------------------------
Adverse reactions occurring greater than or equal to 5% are hypotension,
hyperkalemia, cough, dizziness, and renal failure. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Novartis
Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-
1088 or www.fda.gov/medwatch.
-------------------------------DRUG INTERACTIONS------------------------------
• Avoid concomitant use with aliskiren in patients with estimated glomerular
filtration rate (eGFR) less than 60. (7.1)
• Potassium-sparing diuretics: May lead to increased serum potassium. (7.2)
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): May lead to increased
risk of renal impairment. (7.3)
• Lithium: Increased risk of lithium toxicity. (7.4)
------------------------USE IN SPECIFIC POPULATIONS-----------------------
• Lactation: Breastfeeding not recommended. (8.2)
• Severe Hepatic Impairment: Use not recommended. (2.8, 8.6)
See 17 for PATIENT COUNSELING INFORMATION and FDA-
approved patient labeling.
Revised: 4/2024
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: FETAL TOXICITY
1 INDICATIONS AND USAGE
1.1 Adult Heart Failure
1.2 Pediatric Heart Failure
2 DOSAGE AND ADMINISTRATION
2.1 General Considerations
2.2 Adult Heart Failure
2.3 Pediatric Heart Failure
2.4 Preparation of Oral Suspension Using Tablets
2.5 Preparation and Administration of Oral Pellets
2.6 Dose Adjustment for Patients Not Taking an ACE inhibitor or
ARB or Previously Taking Low Doses of These Agents
2.7 Dose Adjustment for Severe Renal Impairment
2.8 Dose Adjustment for Hepatic Impairment
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Fetal Toxicity
5.2 Angioedema
5.3 Hypotension
5.4 Impaired Renal Function
5.5 Hyperkalemia
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Dual Blockade of the Renin-Angiotensin-Aldosterone System
7.2 Potassium-Sparing Diuretics
7.3 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Including
Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)
7.4 Lithium
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Hepatic Impairment
8.7 Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Adult Heart Failure
14.2 Pediatric Heart Failure
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not
listed.