Usual Adult Dose for Congestive Heart Failure

Initial dose: Sacubitril 49 mg-Valsartan 51 mg orally twice a day

Maintenance dose: Sacubitril 97 mg-Valsartan 103 mg orally twice a day

Comments:

• Increase to the target maintenance dose (sacubitril 97 mg-valsartan 103 mg twice daily) after 2 to 4 weeks, as tolerated.
• For patients not currently taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) and for patients previously taking low doses of these agents, start this drug at half the normally recommended initial dose. After initiation, increase the dose per the recommended dose escalation.

Use: To reduce the risk of cardiovascular death and hospitalization in adult patients with chronic heart failure, especially those with left ventricular ejection fraction (LVEF) below normal.

Usual Pediatric Dose for Congestive Heart Failure

1 Year or Older:
Less than 40 kg: 1.6 mg/kg orally twice a day for 2 weeks, then titrate to 2.3 mg/kg orally twice a day for 2 weeks, and then titrate to 3.1 mg/kg orally twice a day

40 to less than 50 kg: Sacubitril 24 mg-Valsartan 26 mg orally twice a day for 2 weeks, then titrate to sacubitril 49 mg-valsartan 51 mg orally twice a day for 2 weeks, and then titrate to sacubitril 72 mg-valsartan 78 mg orally twice a day

50 kg or greater: Sacubitril 49 mg-Valsartan 51 mg orally twice a day for 2 weeks, then titrate to sacubitril 72 mg-valsartan 78 mg orally twice a day for 2 weeks, and then titrate to sacubitril 97 mg-valsartan 103 mg orally twice a day

Comments:

• Use of the oral suspension is recommended for pediatric patients 1 year or older who weigh less than 40 kg.
• Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan.
• Doses of sacubitril 72 mg-valsartan 78 mg can be achieved using three sacubitril 24 mg-valsartan 26 mg tablets.
• For pediatric patients 1 year or older weighing 50 kg or less who are not currently taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) or who were previously taking low doses of these agents, start this drug at 0.8 mg/kg orally twice a day using the oral suspension. After initiation, increase the dose per the recommended dose escalation.
• For pediatric patients 1 year or older weighing more than 50 kg who are not currently taking an ACE inhibitor or ARB or who were previously taking low doses of these agents, start this drug at half the normally recommended initial dose. After initiation, increase the dose per the recommended dose escalation.

Use: Treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients 1 year or older.

Renal Dose Adjustments

Adult:
Mild to moderate renal dysfunction: No adjustment recommended
Severe renal dysfunction (estimated GFR less than 30 mL/min/1.73 m2): Start this drug at half the normally recommended initial dose. After initiation, increase the dose per the recommended dose escalation.

Pediatric (1 Year or Older):
Mild to moderate renal dysfunction: No adjustment recommended
Severe renal dysfunction (estimated GFR less than 30 mL/min/1.73 m2):

• Less than or equal to 50 kg: Start this drug at 0.8 mg/kg orally twice a day using the oral suspension. After initiation, increase the dose per the recommended dose escalation
• Greater than 50 kg: Start this drug at half the normally recommended initial dose. After initiation, increase the dose per the recommended dose escalation.

Liver Dose Adjustments

Adult:
Mild liver dysfunction: No adjustment recommended
Moderate liver dysfunction (Child-Pugh B): Start this drug at half the normally recommended initial dose. After initiation, increase the dose per the recommended dose escalation.
Severe liver dysfunction: Not recommended

Pediatric (1 Year or Older):
Mild liver dysfunction: No adjustment recommended
Moderate liver dysfunction (Child-Pugh B):

• Less than or equal to 50 kg: Start this drug at 0.8 mg/kg orally twice a day using the oral suspension. After initiation, increase the dose per the recommended dose escalation
• Greater than 50 kg: Start this drug at half the normally recommended initial dose. After initiation, increase the dose per the recommended dose escalation.

Severe liver dysfunction: Not recommended

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to any component
• History of angioedema related to angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy
• Concomitant use of ACE inhibitors; do not administer this drug within 36 hours of switching from or to an ACE inhibitor
• Concomitant use of aliskiren in patients with diabetes

US BOXED WARNING:

• FETAL TOXICITY: If pregnancy is detected, discontinue this drug as soon as possible. Drugs that act directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus.

Safety and efficacy have not been established in patients younger than 1 year.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice: Oral suspension can be substituted at the recommended tablet dosage in patients unable to swallow tablets.

Storage requirements: Oral suspension can be stored for up to 15 days; do not store above 25C (77F) and do not refrigerate.

Reconstitution/preparation techniques: The manufacturer product information should be consulted.

Monitoring:

• Monitor serum potassium periodically, especially in patients with severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet.
• Closely monitor serum creatinine.

Patient advice:

• Females of childbearing age should be informed of the consequences of exposure to this drug during pregnancy; ask these patients to report pregnancies as soon as possible.
• Advise patients to discontinue use of their previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Advise patients to allow a 36 hour wash-out period if switching from or to an ACE inhibitor.

Frequently asked questions

• Does Entresto improve ejection fraction?
• How much does Entresto cost per month?
• Is Entresto a blood thinner and does it lower blood pressure?