Entresto 97 mg/103 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Entresto 24 mg/26 mg film-coated tablets

Entresto 49 mg/51 mg film-coated tablets

Entresto 97 mg/103 mg film-coated tablets

sacubitril/valsartan

Read the entire 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Entresto is and what it is used for

Entresto is a heart medication 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 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 are shortness of breath, fatigue, tiredness, and swelling of the ankles.

2. What you need to know before taking 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 (for example 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 your last dose before starting 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, which can be life-threatening if swelling in the throat blocks the airway) when taking an ACE inhibitor or angiotensin receptor antagonists (ARA) (such as valsartan, telmisartan, or irbesartan).
• if you have had angioedema that is hereditary or of unknown cause (idiopathic).
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing 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 any of these situations, do not take Entresto and speak with 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 (ARA) 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 diarrhoea 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 (for example, a medicine that increases urine production (diuretic)) or have vomiting or diarrhoea, 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 to your kidneys have narrowed.
• if you have renal disease.
• if you experience hallucinations, paranoia, or changes in sleep patterns while taking Entresto.
• if you have hyperkalaemia (high levels of potassium in the blood).
• if you have heart failure classified as NYHA class IV (unable to carry out any physical activity without discomfort and may have symptoms even at rest).

If you are in any 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 monitor your blood pressure at the start of treatment and when doses are 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 aged 1 year and older with a body weight below 40 kg, this medicine will be administered as granules (instead of tablets).

Taking Entresto with other medicines

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines. Your dose may need to be adjusted, additional precautions may be required, or you may need to 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 after your last dose of the ACE inhibitor before starting Entresto (see “Do not take Entresto”). If you stop taking Entresto, wait 36 hours after your last dose of Entresto before starting an ACE inhibitor.
• other medicines used to treat heart failure or lower blood pressure, such as angiotensin receptor antagonists or aliskiren.
• certain medicines known as statins used to lower high cholesterol levels (for example atorvastatin).
• sildenafil, tadalafil, vardenafil, or avanafil, medicines used to treat erectile dysfunction or pulmonary hypertension.
• medicines that increase potassium levels in the blood. This includes potassium supplements, salt substitutes containing potassium, potassium-sparing medicines, and heparin.
• a type of painkiller 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 starting or adjusting your treatment (see “Warnings and precautions”).
• lithium, a medicine used to treat certain psychiatric conditions.
• furosemide, a medicine belonging to a class known as diuretics, used to increase the amount of urine you produce.
• nitroglycerin, a medicine used to treat angina.
• certain types of antibiotics (rifamycin group), cyclosporine (used to prevent rejection of transplanted organs), or antivirals such as ritonavir (used to treat HIV/AIDS).
• metformin, a medicine used to treat diabetes.

If you are in any 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 plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Inform your doctor if you think you are (or might become) pregnant. Your doctor will usually advise you to stop taking this medicine before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine instead of Entresto.

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

Breastfeeding

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

Driving and using machines

Before driving a vehicle, using tools or operating machinery, or engaging in other activities requiring 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; therefore, it is essentially “sodium-free”.

3. How to take Entresto

Follow exactly the instructions for using this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Adults

You will usually start by taking one tablet of 24 mg/26 mg or 49 mg/51 mg twice daily (one tablet in the morning and one tablet in the evening). Your doctor will decide your exact starting dose depending on which medicine you have previously been taking 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 for you is found.

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

Children and adolescents (aged one year and older)

Your doctor (or your child's doctor) will determine the starting dose based on body weight and other factors, including any previous medications taken. The doctor will adjust the dose every 2–4 weeks until the best dose is found.

Entresto should be taken twice daily (one tablet in the morning and one tablet in the evening).

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

Patients taking Entresto may develop low blood pressure (dizziness, lightheadedness), high potassium levels in the blood (which may be detected during blood tests performed by your doctor), or reduced kidney function. If this occurs, your doctor may reduce the dose of any other medications you are taking, temporarily reduce the dose of Entresto, or discontinue your treatment with Entresto completely.

Swallow the tablets with a glass of water. You may take Entresto with or without food. Splitting or crushing the tablets is not recommended.

If you take more Entresto than you should

If you have accidentally taken too many Entresto tablets, or if someone else 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 that you take your medicine at the same time each day. However, if you forget 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 this medicine unless instructed by your doctor.

If you have any further questions about 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 everyone gets them.

Some side effects may 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 (an uncommon side effect that may affect up to 1 in 100 people).

Other possible side effects:

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

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

• low blood pressure, which may cause symptoms such as dizziness and lightheadedness (hypotension)
• high levels of potassium in the blood, detected in blood tests (hyperkalaemia)
• reduced kidney function (renal impairment).

Common (may affect up to 1 in 10 people)

• cough
• dizziness
• diarrhoea
• low red blood cell count, detected in a blood test (anaemia)
• tiredness (fatigue)
• sudden inability of the kidney to function properly (acute renal failure)
• low level of potassium in the blood, detected in a blood test (hypokalaemia)
• 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)
• sensation of spinning (vertigo)
• low blood sugar level, detected in a blood test (hypoglycaemia)

Uncommon (may affect up to 1 in 100 people)

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

Rare (may affect up to 1 in 1,000 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 causing symptoms such as abdominal pain, nausea, vomiting and diarrhoea

Frequency not known (cannot be estimated from available data)

• involuntary muscle jerks (myoclonus)

Reporting of side effects

If you experience any side effect, talk to your doctor, pharmacist or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the national reporting system detailed 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 stated on the packaging and on the blister after CAD/EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage temperature conditions.

Store in the original packaging to protect it 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 and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Entresto

• The active substances 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 salt complex 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 salt complex 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 salt complex of sacubitril, valsartan and sodium).

• Other components in the tablet core are microcrystalline cellulose, low-substituted hydroxypropylcellulose, crospovidone, magnesium stearate, talc and colloidal silicon dioxide (see end of section 2 under '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).

Appearance of the product and contents of the container

Entresto 24 mg/26 mg film-coated tablets are white-violet, oval-shaped 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-shaped 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-shaped 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 available 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 available in multiple packs containing 3 containers, each with 56 tablets.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer responsible for production

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 Nuremberg

Germany

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

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