Entresto

Entresto is an oral combination prescription heart medication that contains two blood pressure-lowering medications: sacubitril and valsartan. Entresto is used to treat adults with long-lasting (chronic) heart failure to help reduce the risk of death and hospitalization and to treat certain children aged 1 year and older who have symptomatic heart failure.

• Adults who benefit the most from Entresto have a left ventricular ejection fraction (LVEF) below normal (this means the heart cannot pump a normal amount of blood around the body).

Entresto contains sacubitril and valsartan, which each have a different mechanism of action. Sacubitril works by blocking neprilysin, an enzyme that breaks down certain peptides in the body. This increases levels of beneficial peptides in the body which relax blood vessels and promote sodium and water excretion into the urine, reducing blood pressure. Valsartan blocks the effects of a hormone called angiotensin II, which can cause blood vessels to narrow and increase blood pressure. Entresto belongs to the class of medicines known as angiotensin receptor-neprilysin inhibitors (ARNi).

Entresto gained FDA approval on July 7, 2015. Entresto is available as oral tablets and Entresto Sprinkle which can be sprinkled on food. Generic Entresto tablets are available under sacubitril and valsartan.

Take Entresto or Entresto Sprinkle exactly as prescribed by your doctor. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

• Entresto or Entresto Sprinkle is taken 2 times each day.

If you or your child cannot swallow tablets, or if tablets are not available in the prescribed strength, you or your child may take Entresto tablets prepared as a liquid (oral) suspension or Entresto Sprinkle.

• Your pharmacist will prepare an oral suspension of Entresto tablets for you.
• Shake the oral suspension (liquid) before you measure a dose.
• Use the dosing syringe provided or a proper dose-measuring device. Do not use a kitchen spoon.

If you or your child are prescribed Entresto Sprinkle:

• Open the capsule(s) and sprinkle the oral pellets onto 1 to 2 teaspoonfuls of soft food. Take right away.
• Do not swallow the capsules.
• Do not chew or crush the oral pellets.
• Use all of the oral pellets in the capsule. Do not use part of a capsule to try to prepare a dose.
• Do not take or give the Sprinkle through a nasogastric tube (NG Tube), gastrostomy tube (G Tube), or other feeding tubes, because the pellets may clog the tube.

Before taking Entresto, tell your doctor about all of your medical conditions, including if you:

• have a history of hereditary angioedema
• have kidney or liver problems
• have diabetes
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Pregnancy

Do not use Entresto if you are pregnant. Stop using and tell your doctor right away if you become pregnant. Entresto can cause injury or death to the unborn baby. If you are a female with childbearing potential, your doctor may ask you to do a pregnancy test before starting Entresto and you should use effective birth control while taking it.

Breastfeeding

It is not known if Entresto or Entresto Sprinkle passes into your breast milk. You should not breastfeed during treatment. Talk to your healthcare provider about the best way to feed your baby during this time.

The most common side effects of Entresto are:

• low blood pressure
• high potassium levels
• cough
• dizziness
• kidney problems.

Serious side effects and warnings

Entresto carries a Boxed Warning for fetal toxicity (harm to an unborn baby).

Entresto or Entresto Sprinkle can harm or cause death to your unborn baby. Talk to your doctor about other ways to treat heart failure if you plan to become pregnant. Do not use Entresto if you are pregnant. Stop using and tell your doctor right away if you become pregnant.

Entresto can cause serious allergic reactions called angioedema which can cause swelling of your face, lips, tongue, and throat that may cause trouble breathing and death. Get emergency medical help right away if you have symptoms of angioedema or trouble breathing and do not take Entresto again. People who are African American, or who have had angioedema before, are at higher risk of developing angioedema. Do not take Entresto if you are allergic to sacubitril, valsartan (Diovan), Entresto, any of the inactive ingredients in the tablets or pellets, or if you have ever had a severe allergic reaction, such as angioedema (a serious swelling under the skin) to a blood pressure medication such as:

• an ACE inhibitor, such as benazepril, captopril, enalapril, or lisinopril, or
• an ARB, such as candesartan, irbesartan, losartan, or telmisartan.

Get emergency medical help if you have signs of an allergic reaction to Entresto such as hives; difficulty breathing; or swelling of your face, lips, tongue, or throat.

Entresto should not be taken with an ACE inhibitor, or within 36 hours of taking one. If you have diabetes or kidney disease, do not use Entresto together with any medication that contains aliskiren (brand names Tekturna or Tekamlo).

Low blood pressure is common during treatment with Entresto, especially if you also take water pills (diuretics). Call your doctor if you become dizzy, lightheaded, or if you develop extreme tiredness (fatigue).

Kidney problems are common during treatment with Entresto and can be serious and can lead to kidney failure. Your healthcare provider will check your kidney function during treatment. Entresto may also increase levels of potassium in your blood and you will also be monitored for this.

Increased amount of potassium in your blood (hyperkalemia). Increased blood potassium levels are common during treatment with Entresto. Your doctor will check your potassium blood level duringyour treatment.

Call your doctor at once if you have:

• a light-headed feeling, like you might pass out
• extreme tiredness
• high potassium - slow heart rate, weak pulse, muscle weakness, tingly feeling or
• kidney problems - little or no urinating, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Entresto adult recommended starting dose: Entresto 49/51 mg 2 times daily.

• Adjust the Entresto dose every 2 to 4 weeks to the target maintenance dose, as tolerated.
• The target maintenance dose is Entresto 97/103mg 2 times daily
• Reduce the starting dose by 50% in patients with moderate liver or severe kidney disease or taking certain other medications. Entresto is not recommended for patients with severe liver disease.

Entresto child recommended starting dose: The dosage of Entresto for children is based on weight.

• Refer to the Entresto Prescribing Information for the recommended Entresto dose and titration schedule.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up for the missed dose.

Dosages are based on weight in children. Your child's dose needs may change if the child gains or loses weight. If you take too much Entresto or Entresto Sprinkle, call your doctor right away, seek emergency medical attention, or call the Poison Help line at 1-800-222-1222.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Do not use potassium supplements or salt substitutes while you are taking Entresto unless your doctor has told you to.

Avoid drinking too much alcohol with Entresto. Drinking alcohol can further lower your blood pressure and may increase certain side effects of Entresto.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking Entresto or Entresto Sprinkle with certain other medicines may affect each other or cause serious side effects. Especially tell your doctor if you take:

• atorvastatin (Lipitor)
• potassium supplements or a salt substitute
• nonsteroidal anti-inflammatory drugs (NSAIDs)
• lithium
• other medicines for high blood pressure or heart problems, such as an ACE inhibitor, ARB, or Aliskiren
• a diuretic or "water pill"
• NSAIDs (nonsteroidal anti-inflammatory drugs) - aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with sacubitril and valsartan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Because of the prescription drug law, known as the Inflation Reduction Act, Medicare can negotiate directly with drug companies to improve access to some of the costliest single-source brand-name Medicare Part B and Part D drugs.

Entresto is one of 10 drugs covered under Medicare Part D that were selected in 2024 for the first cycle of negotiation based on Total Expenditures under Part D and other criteria as required by the law. Negotiations with participating drug companies are ongoing, and any negotiated prices for the first cycle of negotiation is effective from 2026.

Store Entresto tablets or Entresto Sprinkle oral pellets at room temperature between 68°F to 77°F (20°C to 25°C).

• Protect from moisture.

Store bottles of Entresto that have been prepared as an oral suspension at room temperature less than 77°F (25°C) for up to 15 days.

• Do not refrigerate tablets prepared as an oral suspension.

Keep out of the reach of children.

Entresto tablets

Active ingredients: sacubitril and valsartan

Inactive ingredients: colloidal silicon dioxide, crospovidone, low-substituted hydroxypropyl cellulose, magnesium stearate (vegetable origin), microcrystalline cellulose, and talc. Film coat: hypromellose, iron oxide red (E172), polyethylene glycol 4000, talc, and titanium dioxide (E171).

The film coating contains:

• iron oxide black (E172) (24/26 and 97/103 mg tablets)
• iron oxide yellow (E172) (49/51 mg Entresto)

Entresto tablets are available in the following strengths:

• Entresto 24/26 mg (sacubitril 24 mg and valsartan 26 mg)
• Entresto 49/51 mg (sacubitril 49 mg and valsartan 51 mg)
• Entresto 97/103 mg (sacubitril 97 mg and valsartan 103 mg).

When Entresto tablets are made into a suspension the prepared Entresto oral suspension also contains Ora-Sweet SF and Ora-Plus.

Entresto Sprinkle

Inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, magnesium stearate (vegetable origin), microcrystalline cellulose, and talc.

Film-coating: basic butylated methacrylate copolymer, sodium lauryl sulfate, stearic acid, and talc.

Capsule shell: hypromellose and titanium dioxide (E171).

• Iron oxide yellow (15/16 mg)

Printing ink: shellac, propylene glycol, iron oxide red (E172), ammonia solution (concentrated), and potassium hydroxide.

Entresto Sprinkle is available in 2 strengths:

• Entresto 6 mg/6 mg (sacubitril 6 mg and valsartan 6 mg). White cap, number 04 printed on it.
• Entresto 15 mg/16 mg (sacubitril 15 mg and valsartan 16 mg). Yellow cap, number 10 printed on it.

Novartis Pharmaceuticals Corporation makes Entresto.