ENTRESTO 49 mg/51 mg FILM-COATED TABLETS

Introduction

Patient Information Leaflet

Entresto24mg/26mgfilm-coated tablets

Entresto49mg/51mgfilm-coated tablets

Entresto97mg/103mgfilm-coated tablets

sacubitril/valsartan

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Entresto and what is it used for
2. What you need to know before you take Entresto
3. How to take Entresto
4. Possible side effects
5. Storage of Entresto
6. Contents of the pack and other information

1. What is Entresto and what is it used for

Entresto is a heart medicine that contains a neprilysin inhibitor and an angiotensin receptor blocker. It provides two active substances, sacubitril and valsartan.

Entresto is used to treat a type of heart failure in adults, children, and adolescents (from 1 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 are difficulty breathing, fatigue, tiredness, and swelling of the ankles.

2. What you need to know before you take Entresto

Do not take Entresto

• if you are allergic to sacubitril, valsartan, or any of the other ingredients of this medicine (listed in section 6).
• if you are taking another type of medicine called angiotensin-converting enzyme (ACE) inhibitors (e.g., enalapril, lisinopril, or ramipril), which are used to treat high blood pressure or heart failure. If you have been taking ACE inhibitors, wait 36 hours after taking the last dose before starting to take Entresto (see "Other medicines 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 be life-threatening if the swelling of the throat blocks the airway) when taking an ACE inhibitor or angiotensin receptor antagonist (e.g., valsartan, telmisartan, or irbesartan).
• if you have had angioedema that is hereditary or of unknown cause (idiopathic).
• if you have diabetes or kidney damage and are being treated with a blood pressure-lowering medicine that contains aliskiren (see "Other medicines and Entresto").
• if you have severe liver disease.
• if you are more than 3 months pregnant (see "Pregnancy and breastfeeding").

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

Warnings and precautions

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

• if you are being treated with an angiotensin receptor antagonist or aliskiren (see "Do not take Entresto").
• if you have ever had angioedema (see "Do not take Entresto" and section 4 "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 medicine that lowers your blood pressure (e.g., a diuretic) or have vomiting or diarrhea, especially if you are over 65 years old, or if you have liver disease and low blood pressure.
• if you have kidney disease.
• if you are dehydrated.
• if the arteries of your kidney have narrowed.
• if you have kidney disease.
• if you experience hallucinations, paranoia, or changes in sleep patterns while taking Entresto.
• if you have high levels of potassium in the blood (hyperkalemia).
• if you have heart failure classified as NYHA IV (inability to carry out any physical activity without discomfort and may have symptoms even at rest).

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

Your doctor may check the levels of potassium and sodium 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 the dose is increased.

Children and adolescents

Do not give this medicine to children under 1 year of age as it has not been studied in this age group. For children over 1 year of age with a body weight below 40 kg, this medicine will be given as a granule (instead of tablets).

Taking Entresto with other medicines

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

• ACE inhibitors. Do not take Entresto with ACE inhibitors. If you have been taking an ACE inhibitor, wait 36 hours before taking the last dose of the ACE inhibitor before starting to take Entresto (see "Do not take Entresto"). If you stop taking Entresto, wait 36 hours after taking your last dose of Entresto before starting to take an ACE inhibitor.
• other medicines used to treat heart failure or to lower blood pressure, such as angiotensin receptor antagonists or aliskiren.
• certain medicines known as statins, which are used to lower high cholesterol levels (e.g., atorvastatin).
• sildenafil, tadalafil, vardenafil, or avanafil, which are medicines used to treat erectile dysfunction or pulmonary hypertension.
• medicines that increase the amount of potassium in the blood. This includes potassium supplements, salt substitutes that contain potassium, potassium-sparing medicines, and heparin.
• a type of pain reliever called non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors. If you are taking one of these medicines, your doctor may want to check your kidney function when you start or adjust your treatment (see "Warnings and precautions").
• lithium, a medicine used to treat certain psychiatric disorders.
• furosemide, which belongs to a type of medicines known as diuretics, which are used to increase the amount of urine you produce.
• nitroglycerin, a medicine used to treat angina pectoris.
• certain types of antibiotics (rifamycin group), cyclosporine (used to prevent organ rejection after transplantation), or antivirals such as ritonavir (used to treat HIV/AIDS).
• metformin, a medicine used to treat diabetes.

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Tell your doctor if you think you are (or might become) pregnant. Your doctor will normally advise you to stop taking this medicine before you become pregnant or as soon as you know you are pregnant, and will advise you to take another medicine instead of Entresto.

This medicine is not recommended during early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breastfeeding

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

Driving and using machines

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

Entresto contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 97 mg/103 mg dose; i.e., it is essentially "sodium-free".

3. How to take Entresto

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, ask your doctor or pharmacist again.

Adults

Normally, you will start by taking one 24 mg/26 mg or 49 mg/51 mg tablet twice a day (one tablet in the morning and one tablet in the evening). Your doctor will decide your exact initial dose based on what medicine you have been taking before and your blood pressure. Your doctor will then adjust the dose every 2-4 weeks depending on how you respond to treatment until the best dose is found.

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

Children and adolescents (1 year and older)

Your doctor (or your child's doctor) will decide the initial dose based on body weight and other factors, including medicines taken before. The doctor will adjust the dose every 2-4 weeks until the best dose is found.

Entresto must be taken twice a day (one tablet in the morning and one tablet in the evening).

Entresto film-coated tablets must not be used in children with a body weight below 40 kg. For these patients, Entresto granules are available.

Patient's taking Entresto may develop low blood pressure (dizziness, lightheadedness), high levels of potassium in the blood (which can be detected in a blood test), or decreased kidney function. If this happens, your doctor may reduce the dose of one of the other medicines you are taking, temporarily reduce the dose of Entresto, or interrupt treatment with Entresto completely.

Swallow the tablets with a glass of water. You can take Entresto with or without food. It is not recommended to divide or crush the tablets.

If you take more Entresto than you should

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

If you forget to take Entresto

It is recommended to take your medicine 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 make up for forgotten doses.

If you stop taking Entresto

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

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some side effects can be serious

• Stop taking Entresto and seek medical attention immediately 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 may affect up to 1 in 100 people).

Other possible side effects:

If any of the following side effects get serious, tell 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 lightheadedness (hypotension)
• high levels of potassium in the blood, detected in a blood test (hyperkalemia)
• decreased kidney function (renal impairment).

Common(may affect up to 1 in 10 people)

• cough
• dizziness
• diarrhea
• low levels of red blood cells, detected in a blood test (anemia)
• fatigue (tiredness)
• acute inability of the kidney to function properly (renal failure)
• low levels of potassium in the blood, detected in a blood test (hypokalemia)
• headache
• fainting (syncope)
• weakness (asthenia)
• feeling sick (nausea)
• low blood pressure (dizziness, lightheadedness) when standing up from sitting or lying down
• gastritis (stomach pain, nausea)
• feeling of spinning (vertigo)
• low blood sugar levels, detected in a blood test (hypoglycemia)

Uncommon(may affect up to 1 in 100 people)

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

Rare(may affect up to 1 in 1,000 people)

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

Frequency not known(cannot be estimated from the available data)

• involuntary muscle spasms (myoclonus)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Entresto

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

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

Store in the original package to protect from moisture.

Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Entresto

• The active ingredients are sacubitril and valsartan.

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

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

Product Appearance and Packaging Contents

Entresto 24 mg/26 mg film-coated tablets are pale purple, oval tablets with the inscription “NVR” on one side and “LZ” on the other. Approximate tablet dimensions are 13.1 mm x 5.2 mm.

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

Entresto 97 mg/103 mg film-coated tablets are light pink, oval tablets with the inscription “NVR” on one side and “L11” on the other. Approximate tablet dimensions are 15.1 mm x 6.0 mm.

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

Only some pack sizes may be marketed.

Marketing Authorisation Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Pharmaceutical Manufacturing LLC

Verovskova 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 contact the local representative of the marketing authorisation holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.