Patient Information Leaflet

Entresto24mg/26mgfilm-coated tablets

Entresto49mg/51mgfilm-coated tablets

Entresto97mg/103mgfilm-coated tablets

sacubitrilo/valsartán

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not give it to others even if they have similar symptoms to you, as it may harm them.

• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What Entresto is and what it is used for

2.What you need to know before you start taking Entresto

3.How to take Entresto

4.Possible side effects

5.Storage of Entresto

6.Contents of the pack and additional information

Entresto is a heart medication that contains a neprilisin inhibitor and an angiotensin receptor inhibitor. It provides two active principles, sacubitrilo and valsartán.

Entresto is used for the treatment of a type of heart failure in adults, children, and adolescents (from one year of age).

This type of heart failure occurs when the heart is weak and cannot pump enough blood to the lungs and the rest of the body. The most common symptoms of heart failure aredifficulty breathing, fatigue, tiredness, and swelling of the ankles.

Do not take Entresto

• If you are allergic to sacubitril, valsartan, or any of the other components of this medication (listed in section6).
• If you are taking another type of medication called angiotensin-converting enzyme (ACE) inhibitors (such as enalapril, lisinopril, or ramipril), which are used to treat high blood pressure or heart failure. If you have been taking ACE inhibitors, wait 36hours after taking the last dose before starting Entresto (see “Other medications and Entresto”).
• If you have ever had a reaction called angioedema (rapid swelling under the skin in areas such as the face, throat, arms, and legs that can put your life at risk if the swelling of the throat blocks the airway) when taking an ACE inhibitor or angiotensin receptor antagonist (ARA) (such as valsartan, telmisartan, or irbesartan).
• If you have hereditary or unknown cause angioedema (idiopathic).
• If you have diabetes or kidney function damage and are being treated with a medication to lower blood pressure that contains aliskireno (see “Other medications and Entresto”).
• If you have severe liver disease.
• If you are more than 3months pregnant (see “Pregnancy and breastfeeding”).

If you are in one of these cases, do not take Entresto and talk to your doctor.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take or while taking Entresto:

• If you are being treated with an angiotensin receptor antagonist (ARA) or aliskireno (see “Do not take Entresto”).
• If you have ever had angioedema (see “Do not take Entresto” and section4 “Possible side effects”).
• If you experience abdominal pain, nausea, vomiting, or diarrhea after taking Entresto. Your doctor will decide whether to continue treatment. Do not stop taking Entresto on your own.
• If you have low blood pressure or are taking any other medication that lowers your blood pressure (such as a diuretic) or have vomiting or diarrhea, especially if you are over 65years old, or if you have liver disease and low blood pressure.
• If you have kidney disease.
• If you have dehydration
• If your kidney arteries have narrowed.
• If you have kidney disease.
• If you experience hallucinations, paranoia, or changes in sleep patterns while taking Entresto.
• If you have hyperkalemia (high levels of potassium in the blood).
• If you have heart failure classified as NYHA IV (inability to perform any physical activity without discomfort and may have symptoms even at rest).

If you are in one of these cases, talk to your doctor, pharmacist, or nurse before taking Entresto.

Your doctor may check your potassium and sodium levels in your blood at regular intervals during treatment with Entresto. Additionally, your doctor may check your blood pressure at the start of treatment and when increasing doses.

Children and adolescents

Do not give this medication to children under 1year as it has not been studied in this age group. For children 1 year and older with a body weight below40kg, this medication will be administered in granules (instead of tablets).

Taking Entresto with other medications

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medication. It may be necessary to change the dose, take other precautions, or even stop taking one of the medications. This is especially important for the following medications:

• ACE inhibitors. Do not take Entresto with ACE inhibitors. If you have been taking an ACE inhibitor, wait 36hours after taking the last dose of the ACE inhibitor before starting Entresto (see “Do not take Entresto”). If you stop taking Entresto, wait 36hours after taking your last dose of Entresto before starting an ACE inhibitor.
• Other medications used to treat heart failure or lower blood pressure, such as angiotensin receptor antagonists or aliskireno.
• Some medications known as statins that are used to lower high cholesterol levels (such as atorvastatina).
• Sildenafil, tadalafil, vardenafil, or avanafil, which are medications used to treat erectile dysfunction or pulmonary hypertension.
• Medications that increase the amount of potassium in the blood. This includes potassium supplements, salt substitutes that contain potassium, potassium-sparing medications, and heparin.
• A type of pain relievers called nonsteroidal anti-inflammatory drugs (NSAIDs) or selective inhibitors of cyclooxygenase-2 (Cox‑2). If you are taking one of these medications, your doctor may want to check your kidney function when starting or adjusting treatment (see “Warnings and precautions”).
• Lithium, a medication used to treat certain types of psychiatric disorders.
• Furosemide, which belongs to a type of medications known as diuretics, used to increase the amount of urine you produce.
• Nitroglycerin, a medication used to treat angina pectoris.
• Some types of antibiotics (rifamycin group), ciclosporin (used to prevent organ rejection after transplantation), or antivirals such as ritonavir (used to treat HIV/AIDS).
• Metformin, a medication used to treat diabetes.

If you are in one of these cases, talk to your doctor or pharmacist before taking Entresto.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Inform your doctor if you think you are (or may become) pregnant. Your doctor will usually advise you to stop taking this medication before becoming pregnant or as soon as you know you are pregnant, and will advise you to take another medication instead of Entresto.

This medication is not recommended in early pregnancy, and should not be taken when more than 3months pregnant, as it could cause serious harm to your baby if used after the third month of pregnancy.

Breastfeeding

Entresto is not recommended for mothers who are breastfeeding. Inform your doctor if you are breastfeeding or planning to start breastfeeding.

Driving and operating machinery

Before driving a vehicle, using tools, or operating machinery, or engaging in other activities that require concentration, make sure you know how Entresto affects you. If you feel dizzy or very tired while taking this medication, do not drive a vehicle, ride a bike, or use machinery.

Entresto contains sodium

This medication contains less than 1mmol of sodium (23mg) per dose of 97mg/103mg; this is, essentially “sodium-free”.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Adults

Normally, you will start taking one tablet of 24mg/26mg or 49mg/51mg twice a day (one tablet in the morning and one tablet at night). Your doctor will decide your exact initial dose based on the medication you have been taking previously and your blood pressure. Your doctor will then adjust the dose every2-4weeksdepending on how you respond to the treatment until finding the best dose for you.

The recommended target dose is 97mg/103mg twice a day (one tablet in the morning and one tablet at night).

Children and adolescents (one year and older)

Your doctor (or your child's doctor) will decide the initial dose based on your child's weight and other factors, including medications taken previously. The doctor will adjust the dose every2-4weeksuntil finding the best dose.

Entresto should be taken twice a day (one tablet in the morning and one tablet at night)

Entresto film-coated tablets should not be used in children weighing less than 40kg. For these patients, Entresto granules are available.

Patients taking Entresto may develop low blood pressure (dizziness, feeling of faintness), high potassium levels in the blood (which may be detected when your doctor performs a blood test) or decreased kidney function. If this occurs, your doctor may reduce the dose of one of the other medications you are taking, temporarily reduce the Entresto dose, or stop Entresto treatment completely.

Swallow the tablets with a glass of water. You can take Entresto with or without food. Do not recommend dividing or crushing the tablets.

If you take more Entresto than you should

If you accidentally take too many Entresto tablets, or if someone has taken your tablets, contact your doctor immediately. If you experience severe dizziness and/or fatigue, inform your doctor as soon as possible and lie down.

If you forget to take Entresto

It is recommended to take your medication at the same time every day. However, if you have forgotten to take Entresto, simply take the next dose at the scheduled time.Do not take a double dose to compensate for the missed doses.

If you stop taking Entresto

If you stop taking Entresto, your condition may worsen. Do not stop taking your medication unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some side effects can be serious

• Stop taking Entresto and seek immediate medical attention if you notice swelling of the face, lips, tongue, and/or throat, which may cause difficulty breathing or swallowing. These could be signs of angioedema (a rare side effect that can affect up to 1 in 100 people).

Other possible side effects:

If any of the side effects listed below become severe, report them to your doctor or pharmacist.

Very common(may affect more than 1 in 10 people)

• low blood pressure, which can cause symptoms such as dizziness and feeling faint (hypotension)
• high levels of potassium in the blood, detected by blood test (hyperkalemia)
• reduced kidney function (renal insufficiency).

Common(may affect up to 1 in 10 people)

• cough
• dizziness
• diarrhea
• low red blood cell count, detected by blood test (anemia)
• fatigue (tiredness)
• acute kidney failure (renal failure)
• low potassium levels in the blood, detected by blood test (hypokalemia)
• headache
• syncope (fainting)
• weakness (asthenia)
• nausea (feeling que you are going to be sick)
• low blood pressure (dizziness, feeling faint) when changing from sitting or lying down to standing
• gastritis (stomach pain, nausea)
• dizziness (vertigo)
• low blood sugar, detected by blood test (hypoglycemia)

Rare(may affect up to 1 in 100 people)

• allergic reaction with rash and itching (hypersensitivity)
• dizziness when changing from sitting to standing (postural dizziness)
• low sodium levels in the blood, detected by blood test (hyponatremia)

Very rare(may affect up to 1 in 10,000 people)

• seeing, hearing, or feeling things that are not there (hallucinations)
• changes in sleep pattern (sleep disorder)

Very rare(may affect up to 1 in 10,000 people)

• paranoia
• intestinal angioedema: swelling in the intestine that causes symptoms such as abdominal pain, nausea, vomiting, and diarrhea

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and in the blister pack after CAD/EXP. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature.

Store in the original packaging to protect it from moisture.

Do not use this medication if you observe that the packaging is damaged or shows signs of handling.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Entresto

• The active ingredients are sacubitril and valsartan.

• Each film-coated tablet of 24 mg/26 mg contains 24.3 mg of sacubitril and 25.7 mg of valsartan (as a complex salt of sacubitril, valsartan, and sodium).
• Each film-coated tablet of 49 mg/51 mg contains 48.6 mg of sacubitril and 51.4 mg of valsartan (as a complex salt of sacubitril, valsartan, and sodium).
• Each film-coated tablet of 97 mg/103 mg contains 97.2 mg of sacubitril and 102.8 mg of valsartan (as a complex salt of sacubitril, valsartan, and sodium).

• The other components in the tablet core are microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crospovidone, magnesium stearate, talc, and colloidal silicon dioxide (see the end of section 2 in ‘Entresto contains sodium’).
• The film coatings of the 24 mg/26 mg and 97 mg/103 mg tablets contain hypromellose, titanium dioxide (E171), Macrogol (4000), talc, iron oxide red (E172), and iron oxide black (E172).
• The film coating of the 49 mg/51 mg tablets contains hypromellose, titanium dioxide (E171), Macrogol (4000), talc, iron oxide red (E172), and iron oxide yellow (E172).

Appearance of the product and contents of the pack

Entresto 24 mg/26 mg film-coated tablets are white to pale violet, oval-shaped tablets with the inscription “NVR” on one side and “LZ” on the other. The approximate dimensions of the tablets are 13.1 mm x 5.2 mm.

Entresto 49 mg/51 mg film-coated tablets are pale yellow, oval-shaped tablets with the inscription “NVR” on one side and “L1” on the other. The approximate dimensions of the tablets are 13.1 mm x 5.2 mm.

Entresto 97 mg/103 mg film-coated tablets are pale pink, oval-shaped tablets with the inscription “NVR” on one side and “L11” on the other. The approximate dimensions of the tablets are 15.1 mm x 6.0 mm.

The tablets are presented in packs containing 14, 20, 28, 56, 168, or 196 tablets and in multiple packs which include 7 packs, each containing 28 tablets. The 49 mg/51 mg and 97 mg/103 mg tablets are also presented in multiple packs which include 3 packs, each containing 56 tablets.

Only some pack sizes may be marketed.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible for manufacturing

Novartis Pharmaceutical Manufacturing LLC

Verovška Ulica 57

1000 Ljubljana

Slovenia

Novartis Farma S.p.A

Via Provinciale Schito 131

80058 Torre Annunziata (NA)

Italy

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Germany

LEK farmacevtska družba d.d., Poslovna enota PROIZVODNJA LENDAVA

Trimlini 2D

Lendava 9220

Slovenia

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of the summary of product characteristics:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.