Entresto is a medication that combines sacubitril and valsartan. It has the potential to be used to treat heart failure.

Once absorbed, sacubitril is converted into its active form, sacubitrilat (LBQ657). This inhibits the effects of neprilysin, an enzyme that naturally cleaves peptides like ANP, BNP, and CNP that are released when the heart is stressed. Sacubitril increases the concentration of these peptides by inhibiting neprilysin, resulting in vasodilation (blood vessel dilation), natriuresis (an increase in sodium excretion in the urine), and diuresis (an increase in the production of urine). Sacubitril belongs to the angiotensin receptor neprilysin inhibitor (ARNI) class of drugs.

Valsartan works by preventing angiotensin II from binding to the AT1 receptor in blood vessels and other tissues such as the adrenal gland. Angiotensin II is a potent vasoconstrictor (narrows blood vessels) that is also involved in aldosterone synthesis and release (the main steroid hormone produced by the adrenal gland). Valsartan opens the arteries (vasodilates) and lowers blood pressure by inhibiting the actions of angiotensin II. Valsartan is in a class of drugs known as angiotensin II receptor antagonists (also called angiotensin II receptor blockers or ARBs).

In adults with chronic heart failure (NYHA class II-IV) and a low ejection fraction, it may be used to reduce the risk of death and hospitalization.

It may also be given to children aged one year and older with symptomatic heart failure and systemic left ventricular systolic dysfunction to improve outcomes and reduce NT-proBNP.

Entresto is used in place of ACE inhibitors or ARBs, but with other standard heart failure treatments such as beta-blockers or aldosterone antagonists.

For mild-to-moderate kidney disease, no dosage adjustments are required.

You are more likely to experience the following side effects if you are between the ages of 18 and 60, do not take any other medications, or have any other medical conditions:

• The most frequent side effects include low blood pressure, elevated potassium levels in the blood, a cough, lightheadedness, and kidney dysfunction. People who have previously taken other medications that have caused coughs, such as ACE inhibitors, are at a higher risk of developing one. Those who are receiving diuretic therapy, have sodium deficiency, or are dehydrated have a higher risk of developing low blood pressure.
• Angioedema is a rapid swelling beneath the skin and mucus membranes that is usually associated with an allergy to a specific substance, in this case, Entresto. Discontinue Entresto immediately, and if necessary, provide airway support and other appropriate therapy. Do not reintroduce Entresto.
• Gastrointestinal disturbances, sinusitis, stuffy nose, low sodium levels, joint pain, back pain, and muscle cramps may also occur.
• Entresto may not be appropriate for some people who have pre-existing kidney disease, liver disease, severe heart failure, or dehydration; or additional monitoring may be required.
• Lithium, aliskiren, NSAIDs, and potassium supplements may interact with this medication.
• If used during pregnancy, it can result in severe birth defects and fetal death. Entresto should not be given to pregnant women and should be stopped immediately if pregnancy is detected unless no other treatment is available and the benefits outweigh the risks.
• Entresto should be gradually increased over two to four weeks. Adults should begin with Entresto 49/51mg twice daily, which should be increased to Entresto 97/103mg twice daily after two to four weeks. Children can be given an oral suspension made from crushed Entresto 49/51mg tablets mixed with Ora-Plus and Ora-Sweet. Children's dosages are determined by their weight.
• In patients with liver disease, the dosage must be adjusted.
• Potassium levels and kidney function should be checked on a regular basis.
• Patients should be monitored for signs and symptoms of heart failure once Entresto is started. BNP levels should not be used as an indicator of heart failure because Entresto inhibits BNP breakdown and thus raises them.
• There is no generic version available.

In general, people who are older or younger, have certain medical conditions (like liver or kidney issues, heart disease, diabetes, or seizure disorders), take other medications, or are seniors or young children are more likely to experience a wider range of side effects.

Given to adults and children over one, Entresto is a combination drug that contains sacubitril and valsartan to treat heart failure. It is more effective than enalapril at lowering the risk of hospitalization for heart failure and cardiovascular death, according to studies.

Entresto is typically administered twice daily. It is safe to take with or without food.

Any signs or symptoms of angioedema (swelling of the face or throat, difficulty breathing) should be reported to your doctor right away.

May cause a drop in blood pressure that manifests as light-headedness; consult your doctor for guidance; symptoms usually resolve with continued therapy. Take care not to become dehydrated.

Do not use potassium-containing salt substitutes without first consulting your doctor.

Entresto is typically used in conjunction with other medications to lower blood pressure, and you should abide by all dietary and lifestyle advice given to you by your doctor (such as losing weight if overweight, quitting smoking, engaging in regular exercise, and limiting your sodium intake). In addition, other conditions need to be managed, such as high cholesterol or diabetes if present.

Do not take any additional medications, including those purchased over-the-counter, unless your doctor or pharmacist has confirmed that they are safe to take with Entresto.

In clinical trials, Entresto outperformed enalapril in lowering the risk of cardiovascular death or hospitalization for heart failure. Entresto also increased overall survival rates. These findings were consistent across all subgroups studied.

Entresto reduced baseline NT-proBNP in children aged one to less than 18 years by 44% compared to 33% with enalapril, indicating improved cardiovascular outcomes in pediatric patients.

Medicines that interact with Entresto may reduce its effect, shorten its duration of action, increase side effects, or have no effect when combined. An interaction between two medications does not always necessitate the discontinuation of one of them; however, it can. Consult your doctor about how to handle drug interactions.

Entresto may interact with the following medications:

• 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 diabetes medications may need to consult their doctor about adjusting the dose of their medication.

Please keep in mind that this list is not exhaustive and only includes common medications that may interact with Entresto. For a complete list of interactions, consult the Entresto prescribing information.