Sacubitril and valsartan

What is Sacubitril and valsartan?

It is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker. The complex is chemically described as Octadecasodiumhexakis(4-{[(1S,3R)-1-([1,1´-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl]amino}-4-oxobutanoate)hexakis(N-pentanoyl-N-{[2´-(1H-tetrazol-1-id-5-yl)[1,1´-biphenyl]-4-yl]methyl}-L-valinate)—water (1/15).

Valsartan and sacubitril

What are the uses of this medicine?

• It 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.
• It is indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. It reduces NT-proBNP and is expected to improve cardiovascular outcomes.

How does this medicine work?

It contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. ENTRESTO inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT1) receptor via valsartan. The cardiovascular and renal effects of this medicine in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan. Valsartan inhibits the effects of angiotensin II by selectively blocking the AT1 receptor, and also inhibits angiotensin II-dependent aldosterone release.

Who Should Not Use this medicine?

• It is contraindicated in patients with hypersensitivity to any component
• It is contraindicated in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy.
• It is contraindicated with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor.
• It is contraindicated with concomitant use of aliskiren in patients with diabetes.

What are the brand names and dosage forms of this medicine?

• Brand name: Entresto; NDC codes: 0078-0659-20, 0078-0659-35, 0078-0659-61, 0078-0659-67, 0078-0696-20, 0078-0696-35, 0078-0696-61, 0078-0696-67, 0078-0777-20, 0078-0777-35, 0078-0777-61, 0078-0777-67.
• ENTRESTO is supplied as unscored, ovaloid, film-coated tablets in the following strengths:

1. ENTRESTO 24/26 mg, (sacubitril 24 mg and valsartan 26 mg) are violet white and debossed with “NVR” on one side and “LZ” on the other side.
2. ENTRESTO 49/51 mg, (sacubitril 49 mg and valsartan 51 mg) are pale yellow and debossed with “NVR” on one side and “L1” on the other side.
3. ENTRESTO 97/103 mg, (sacubitril 97 mg and valsartan 103 mg) are light pink and debossed with “NVR” on one side and “L11” on the other side.

Is this medicine FDA approved?

It is approved by US FDA on Jul 7, 2015 for heart failure and on Oct 1, 2019 for pediatric heart failure.

What are the active and inactive ingredients in Sacubitril and valsartan?

• Active ingredient:

1. Sacubitril
2. Valsartan

• Inactive ingredient:

1. Cellulose, Microcrystalline
2. Crospovidone
3. Magnesium Stearate
4. Talc
5. Silicon Dioxide
6. Hydroxypropyl Cellulose, Low Substituted
7. Hypromelloses
8. Titanium Dioxide
9. Polyethylene Glycol 4000
10. Ferric Oxide Red
11. Ferrosoferric Oxide

How should this medicine be used?

• Take ENTRESTO exactly as your doctor tells you to take it.
• Take ENTRESTO 2 times each day. Your doctor may change your dose of ENTRESTO during treatment.
• If your child cannot swallow tablets, or if tablets are not available in the prescribed strength, your pharmacist will prepare ENTRESTO as a liquid suspension for your child. If your child switches between taking the tablet and the suspension, your doctor will adjust the dose as needed. Shake the bottle of suspension well before measuring the dose of medicine to give to your child.
• If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Take the next dose at your regular time.
• If you take too much ENTRESTO, call your doctor right away.

What side effects can this medication cause?

• Angioedema
• Hypotension
• Impaired Renal Function
• Hyperkalemia

What to do in case of emergency/overdose?

• Hypotension is the most likely result of overdosage due to the blood pressure lowering effects of ENTRESTO. Symptomatic treatment should be provided.
• ENTRESTO is unlikely to be removed by hemodialysis because of high protein binding.
• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• ENTRESTO 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.

Can this medicine be used in children?

• The safety and effectiveness of ENTRESTO in pediatric heart failure patients 1 to < 18 years old are supported by the reduction from baseline to 12 weeks in NT-proBNP in a randomized, double-blind clinical study. The analysis of NT-proBNP included 90 patients age 6 to 18 years and 20 patients age 1 to 6 years.
• Safety and effectiveness have not been established in pediatric patients less than 1 year of age.

What should I know about storage and disposal of this medication?

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.

• Dailymed label info on Sacubitril and valsartan
• FDA Sacubitril and valsartan

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