Entresto: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on May 17, 2024.

1. How it works

• Entresto is a combination medicine that contains sacubitril and valsartan. It may be used to treat heart failure.
• Sacubitril is converted into its active form, called sacubitrilat (LBQ657) once absorbed. This blocks the effects of neprilysin, an enzyme that would naturally cleave peptides, such as ANP, BNP, and CNP which are released when the heart is under stress. By inhibiting neprilysin, sacubitril increases the concentration of these peptides resulting in vasodilation (opening up of the blood vessels), natriuresis (an increase in the excretion of sodium in the urine), and diuresis (an increase in the production of urine). Sacubitril belongs to the class of medicines known as angiotensin receptor neprilysin inhibitor (ARNI).
• Valsartan works by blocking the binding of angiotensin II to the AT1 receptor in blood vessels and other tissues, such as the adrenal gland. Angiotensin II is a powerful vasoconstrictor (narrows blood vessels), that is also involved in the synthesis and release of aldosterone (the main steroid hormone produced by the adrenal gland). By inhibiting the actions of angiotensin II, valsartan opens up the arteries (vasodilates) and lowers blood pressure. Valsartan belongs to a group of medicines known as angiotensin II receptor antagonists (also called angiotensin II receptor blockers or ARBs).

2. Upsides

• May be used to reduce the risk of death and hospitalization in adults with chronic heart failure (NYHA class II-IV) and a reduced ejection fraction.
• May also be given to improve outcomes and reduce NT-proBNP in children aged one year and older with symptomatic heart failure with systemic left ventricular systolic dysfunction.
• Entresto is used instead of ACE inhibitors or ARBs but is usually combined with other standard heart failure treatments, such as beta-blockers or aldosterone antagonists.
• No dosage adjustment is needed for mild-to-moderate kidney disease.
• Available as oral tablets and an Entresto Sprinkle formulation. The oral tablets can be crushed and made into a suspension for people who have swallowing difficulties. Alternatively, Entresto Sprinkle can be prescribed. The Entresto Sprinkle capsule can be opened and the oral pellets inside sprinkled onto 1 to 2 teaspoonfuls of soft food and swallowed right away.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Low blood pressure, increased blood levels of potassium, a cough, dizziness, and kidney dysfunction are the most common side effects. The risk of a cough is higher in people who have experienced other drug-induced coughs, such as with ACE inhibitors. The risk of low blood pressure is higher in those on diuretic therapy or who are sodium-depleted or dehydrated
• May rarely cause angioedema, which is a rapid swelling beneath the skin and mucus membranes, usually associated with an allergy to a particular substance, in this case, Entresto. Discontinue Entresto immediately, provide airway support if necessary, and other appropriate therapy. Do not reinstate Entresto.
• May also cause gastrointestinal disturbances, sinusitis, stuffy nose, low sodium levels, joint pain, back pain, and muscle cramps.
• Entresto may not be suitable for some people with certain pre-existing kidney conditions, liver disease, severe heart failure, or dehydration; or increased monitoring may be required.
• May interact with several other drugs including lithium, aliskiren, NSAIDs, and potassium supplements.
• Can cause severe birth defects and fetal death if used during pregnancy. Entresto should not be given to pregnant women and should be discontinued immediately if pregnancy is detected unless no alternative treatment is available and the benefits are deemed to outweigh the risks.
• Entresto needs to be titrated upwards slowly, over two to four weeks. The recommended starting dose for adults is Entresto 49/51 twice daily, which should be doubled after two to four weeks to Entresto 97/103mg twice daily. An oral suspension can be made for children using Entresto 49/51mg tablets crushed and mixed with Ora-Plus and Ora-Sweet. Dosages for children are based on weight.
• A dosage adjustment is needed in people with liver impairment.
• Potassium levels and kidney function should be monitored regularly.
• Once Entresto is started, patients should be monitored for signs and symptoms of heart failure. Do not use levels of BNP as an indicator of heart failure, because these will be elevated by Entresto because it inhibits the breakdown of BNP.
• No generic version is available.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Entresto is a combination medication containing sacubitril and valsartan that may be given to treat heart failure in adults and children over the age of one. Studies have shown it to be superior to enalapril at reducing the risk of hospitalizations due to heart failure and cardiovascular death.

5. Tips

• Entresto is usually given twice daily.
• May be taken with or without food.
• Report any signs or symptoms of angioedema (swelling of the face or throat, difficulty breathing) immediately to your doctor.
• May cause a fall in blood pressure that may be noticed as light-headedness; call your doctor and ask for advice, symptoms usually resolve with continued therapy. Ensure you do not become dehydrated.
• Do not use salt substitutes containing potassium without first consulting your doctor.
• Entresto is usually used in addition to other drugs to lower blood pressure, and all lifestyle recommendations given to you by your doctor (such as losing weight if overweight, smoking cessation, partaking in regular exercise, and limiting sodium intake) should also be followed. In addition, other conditions, such as high cholesterol levels or diabetes if present, also need to be controlled.
• Do not take any other medications including those bought over-the-counter without checking with your doctor or pharmacist that they are compatible with Entresto.

6. Response and effectiveness

• Comparative trials have shown that Entresto was superior to enalapril in reducing the risk of cardiovascular death or hospitalization for heart failure. Entresto also improved overall survival. These results were consistent across all subgroups analyzed.
• In children aged one to less than 18 years, Entresto reduced baseline NT-proBNP by 44% compared to 33% with enalapril, indicating improved cardiovascular outcomes in pediatric patients.

7. Interactions

Medicines that interact with Entresto may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Entresto. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Entresto include:

• antipsychotics, such as aripiprazole, clozapine, or haloperidol
• aspirin
• bupropion
• buprenorphine
• corticosteroids, such as budesonide, betamethasone, or prednisone
• cyclosporine
• heart medications, including all ACE inhibitors or ARBs, such as benazepril, captopril, fosinopril, or lisinopril
• insulin
• NSAIDs, such as diclofenac, ibuprofen, or indomethacin
• other heart medications, such as amiodarone, clonidine, digoxin, diltiazem, propafenone, quinidine, and verapamil
• other medications including celecoxib, clonidine, hydralazine, and rifampicin
• potassium salts
• potassium-sparing diuretics such as spironolactone, triamterene, or amiloride
• sildenafil
• trimethoprim
• zolpidem.

People taking oral medications for diabetes may need to talk to their doctor about adjusting the dose of their medicine.

Note that this list is not all-inclusive and includes only common medications that may interact with Entresto. You should refer to the prescribing information for Entresto for a complete list of interactions.

References

• Entresto (sacubitril and valsartan) [Package Insert] Updated 02/2024. Novartis Pharmaceuticals Corporation. https://www.drugs.com/pro/entresto.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Entresto only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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