Sacubitril/ Valsartan (Entresto, Uperio, Sacvin) - for Heart Failure

Sacubitril has a diuretic effect because it stops natriuretic peptides from degrading. Patients with decreased ejection fraction and NYHA class II or higher symptomatic heart failure are eligible for it. It frequently co-administers with medications for heart failure such as ACE inhibitors and angiotensin receptor blockers. In patients with a decreased ejection fraction and symptomatic heart failure who can tolerate ACE inhibitors or ARBs, the ACC/AHA/HFSA advises treatment with sacubitril-valsartan. According to recent research, it may increase the ejection fraction in individuals with decompensated heart failure by up to 10%.

Sacubitril/ valsartan Dose in Adults

The drug is a compound of sacubitril and valsartan available as 24/26 mg, 49/51 mg, 97/103 mg. 26 mg, 51 mg, and 103 mg valsartan in entresto is equivalent to 40, 80, and 160 mg of valsartan in other brands. When initiating sacubitril and valsartan in patients already on an ACE inhibitor or ARBs, a washout period of three days is recommended. Concomitant use of an ACE inhibitor and an ARB is contraindicated.

Patients on a high dose of ACE inhibitor (10 mg of an ACE inhibitor or equivalent or 160 mg of valsartan or equivalent):

  • Start with 49 mg of sacubitril and 51 mg of valsartan twice daily.
  • A goal maintenance dose of 97 mg of sacubitril and 103 mg of valsartan twice daily may be reached by doubling the dose every 2-4 weeks.

Patients previously on a low dose of ACE inhibitor (less than 10 mg per day) or ARB (less than 160 mg of valsartan) & those not taking an ACE inhibitor or ARB:

  • Initiate sacubitril 24 mg/valsartan 26 mg twice daily.
  • The dose may be doubled every 2-4 weeks to a target maintenance dose of 97mg of sacubitril and 103 mg of valsartan twice daily.

Sacubitril/ valsartan Dose in Children

Not recommended for use in children

Pregnancy category X

  • Entresto is not recommended for use during pregnancy. 
  • Fetal death can result from drugs that act on the renin angiotensin system. 
  • It is important to stop using the drug as soon as you can.

Entresto during lactation and breastfeeding

  • It is unknown if the drug is absorbed into breast milk.
  • Due to possible adverse effects on the infant who is breastfeeding, the manufacturer suggests that you avoid sacubitril/valsartan.

Sacubitril/ valsartan dose in Renal disease:

  • eGFR of 30 ml/min/1.73 m2 or more:

    • No dose adjustment is necessary
  • eGFR of les than 30 ml/min/1.73 m2:

    • Sacubitril 24/ valsartan 26 mg twice daily.
    • Some experts advise against its use.

Sacubitril/ valsartan dose in Liver disease:

  • Mild hepatic impairment (Child Class A):

    • No dose adjustment is necessary.
  • Moderate hepatic impairment (Child Class B):

    • Give a lower dose, for as 24 mg of sacubitril and 26 mg of valsartan.
  • Severe hepatic impairment (Child Class C):

    • Avoid using sacubitril (Not studied in this sub-group.

Common side effects of Entresto:

Less common side effects:

  • Orthostatic hypotension, dizziness, vertigo, anemia, hypersensitivity reactions, angioedema, cough, and renal failure.

Contraindications to sacubitril/ vasartan include

  • Severe hypersensitivity reactions to valsartan, sacubitril, or any other formulation ingredient.

  • Angioedema:

    • Patients with hereditary angioneurotic edema and angioedema after the use of ACE inhibitors and ARBs.
  • Serious allergic reactions to ACE inhibitors.

  • Use of an ACE inhibitor, ARB, or direct renin inhibitor concurrently within the last 36 hours.

  • Symptomatic hypotension

  • Pregnancy & Lactation

    • Regardless of the cause, entresto is contraindicated in individuals with a history of angioedema, according to ACC/AHA/HFSA guidelines.

Warnings & Precautions:

  • Hyperkalemia:
    • When using Entresto, patients with impaired renal function, diabetes mellitus, high potassium diets, potassium supplements, hyperaldosteronism, or those taking Aliskiren (contraindicated with concurrent usage) may have hyperkalemia.
  • Hypotension:

    • Patients who are dehydrated, on diuretics, or who have just experienced a myocardial infarction may experience hypotension.
    • Hypotension can also be caused by anesthetic agents. Other blood pressure drugs should not be used during surgery.
  • Inadequate renal function:

    • Small deterioration may be noted after initiating sacubitril/ valsartan.
    • Patients with impaired renal blood flow, such as those suffering from renal artery narrowing, may experience progressive deterioration of their renal functions.

Monitoring Parameters:

  • Renal functions,
  • Blood pressure, and
  • serum Potassium.
  • The ACCF/AHA Heart Failure guidelines recommend monitoring renal functions, Blood pressure, and serum potassium one to two weeks after initiating ACE inhibitor or ARBs.

How to take Entresto?

Take the drug (sacubitril/valsartan) with or without food.

Mechanism of Action of sacubitril/ valsartan:

  • Sacubitril blocks the enzyme Neprilysin, which degrades natriuretic amino peptides. In response to cardiac dilatation, natriuretic peptides can be released.
  • Cardiac dilatation can occur due to fluid overload, secondary to weak heart and pump failure.
  • Valsartan directly inhibits the angiotensin receptors and antagonizes the angiotensin-induced vasoconstriction, release of aldosterone & catecholamine, and prevents cardiac remodeling.


  • is 60%.


  • Valsartan is minimally metabolized.
  • Esterases change sacubitril into the active metabolite LBQ657.

Half-life elimination:

  • Sacubitril: 1.4 hours, LBQ657: 11.5 hours,
  • Valsartan: 9.9 hours


  • Valsartan is eliminated through the stools, while sacubitril is eliminated through the urine.

International Brands of Sacubitril Valsartan:

  • Azmada
  • Entresto
  • Sacutrend
  • Uperio
  • Vacubitron

Sacubitril/ valsartan brands in Pakistan:

Sacvin (Pharmevo) - 24/26 mg, 49/51 mg, 97/103 mg

Uperio (Novartis) - 49/51 mg, 97/103 mg