Package leaflet: Information for the patient

Entresto 24 mg/26 mg film-coated tablets, 49 mg/51 mg film-coated tablets, 97 mg/103 mg film-coated tablets

sacubitril/valsartan
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. 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 other people, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Entresto is and what it is used for
What you need to know before taking Entresto
How to take Entresto
Possible side effects
How to store Entresto
Contents of the pack and other information

1. What Entresto is and what it is used for

Entresto is a heart medicine containing a neprilysin inhibitor and an angiotensin receptor blocker. It releases two active substances, sacubitril and valsartan.
Entresto is used to treat a type of long-term 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, breathlessness, 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 an angiotensin-converting enzyme (ACE) inhibitor (for example enalapril, lisinopril, or ramipril), which is used to treat high blood pressure or heart failure. If you are taking an ACE inhibitor, wait 36 hours after taking the 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 of the throat blocks the airway) while taking an ACE inhibitor or an angiotensin receptor blocker (ARB) (such as valsartan, telmisartan, or irbesartan).
if you have a history of 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 any of these apply to you, do not take Entresto and speak to your doctor.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before or while taking Entresto

if you are being treated with an angiotensin receptor blocker (ARB) or with aliskiren (see "Do not take Entresto").
if you have ever had angioedema (see "Do not take Entresto" and section 4 "Possible side effects").
if, after taking Entresto, you experience abdominal pain, nausea, vomiting, or diarrhoea. Your doctor will decide whether treatment should continue. Do not stop taking Entresto on your own.
if you have low blood pressure or are taking any other medicine to lower blood pressure (for example, a medicine that increases urine production (diuretic)), or if you have vomiting or diarrhoea, especially if you are 65 years of age or older or have kidney disease and low blood pressure.
if you have kidney disease.
if you are dehydrated.
if you have narrowing of a renal artery.
if you have liver 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 suffer from heart failure classified as NYHA class IV (unable to carry out any physical activity without discomfort and may experience symptoms even at rest).

If any of these apply to you, inform your doctor, pharmacist, or nurse before taking Entresto.
Your doctor may check your blood potassium and sodium levels at regular intervals during treatment with Entresto. In addition, your doctor may monitor your blood pressure at the beginning 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 body weight below 40 kg, this medicine will be given as granules (instead of tablets).

Other medicines and Entresto
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. It may be necessary to adjust the dose, take additional precautions, or even discontinue one of these medicines. This is particularly important for the following medicines:

ACE inhibitors. Do not take Entresto with ACE inhibitors. If you are being treated with an ACE inhibitor, wait 36 hours after taking the last dose of the ACE inhibitor before starting Entresto (see "Do not take Entresto"). If you stop taking Entresto, wait 36 hours after taking the last dose of Entresto before starting an ACE inhibitor.
other medicines used to treat heart failure or lower blood pressure, such as angiotensin receptor blockers or aliskiren (see "Do not take Entresto").
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. These include potassium supplements, potassium-containing salt substitutes, potassium-sparing medicines, and heparin.
painkillers of the type known as non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (Cox-2) inhibitors. If you are taking one of these, your doctor may wish to monitor your kidney function when starting or adjusting treatment (see "Warnings and precautions").
lithium, a medicine used to treat certain psychiatric disorders.
furosemide, a medicine belonging to the diuretic class, used to increase urine production.
nitroglycerin, a medicine used to treat angina pectoris.
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 any of these apply to you, inform your doctor or pharmacist before taking Entresto.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming 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 if you are more than 3 months pregnant, as it may cause serious harm to the unborn child if taken after 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, operating tools or machinery, or performing 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, ride a bicycle, or use tools or machinery.

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

3. How to take Entresto

Take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.

Adults
You will usually start by taking either 24 mg/26 mg or 49 mg/51 mg tablets twice daily (one tablet in the morning and one tablet in the evening). Your doctor will decide the exact starting dose based on the medicines you were previously taking and your blood pressure. Your doctor will then adjust the dose every 2–4 weeks, depending on your response to treatment, until the most suitable dose for you is reached.
The usual recommended optimal dose is 97 mg/103 mg twice daily (one tablet in the morning and one tablet in the evening).

Children and adolescents (from one year of age)
Your doctor (or your child’s doctor) will determine the starting dose based on body weight and other factors, including previously taken medicines. Your doctor will adjust the dose every 2–4 weeks until the optimal dose is identified.
Entresto should be given twice daily (one tablet in the morning and one tablet in the evening).
Entresto film-coated tablets are not intended for use in children weighing less than 40 kg. For these patients, Entresto granules are available.

Patients being treated with Entresto may develop low blood pressure (dizziness, feeling of emptiness in the head), high potassium levels in the blood (detected when your doctor performs a blood test), or reduced kidney function. If this occurs, your doctor may reduce the dose of any medicines you are taking, temporarily reduce the dose of Entresto, or stop 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 fainting, inform your doctor as soon as possible and lie down.

If you forget to take Entresto
It is recommended to take the medicine at the same time every day. However, if you forget to take a dose, simply take the next dose at the scheduled time. Do not take a double dose to make up for the missed dose.

If you stop taking Entresto
Stopping treatment with Entresto may cause your condition to worsen. Do not stop taking this medicine unless your doctor tells you to.

If you have any doubts about how to use this medicine, consult 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 immediate medical help if you notice any swelling of the face, lips, tongue and/or throat, which may cause difficulty in breathing or swallowing. These may 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 worsen, inform your doctor or pharmacist.
Very common (may affect more than 1 in 10 people)

low blood pressure which may cause symptoms of dizziness and lightheadedness (hypotension)
high levels of potassium in the blood shown by a blood test (hyperkalaemia)
reduced kidney function (renal impairment)

Common (may affect up to 1 in 10 people)

cough
dizziness
diarrhoea
low levels of red blood cells in the blood shown by a blood test (anaemia)
tiredness (fatigue)
sudden inability of the kidney to work properly (renal failure)
low levels of potassium in the blood shown by a blood test (hypokalaemia)
headache
fainting (syncope)
weakness (asthenia)
feeling unwell (nausea)
low blood pressure (dizziness, lightheadedness) when moving from a sitting or lying position to a standing position
gastritis (stomach pain, nausea)
sensation of dizziness (vertigo)
low levels of sugar in the blood shown by a blood test (hypoglycaemia)

Uncommon (may affect up to 1 in 100 people)

allergic reaction with rash and itching (hypersensitivity)
dizziness when moving from a sitting to a standing position (postural dizziness)
low levels of sodium in the blood shown by a blood test (hyponatraemia)

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

seeing, hearing or sensing things that are not there (hallucinations)
changes in the way of sleeping (sleep disorders)

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

paranoia
intestinal angioedema: swelling in the intestine which presents with symptoms such as abdominal pain, nausea, vomiting and diarrhoea

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.
Not known (frequency cannot be estimated from the available data)

sudden involuntary muscle twitch (myoclonus)

5. How to store Entresto

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Store in the original packaging to protect the medicine from moisture.
Do not use this medicine if the packaging is damaged or shows any signs of tampering.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Entresto contains

The active substances are sacubitril and valsartan.
o Each 24 mg/26 mg film-coated tablet contains 24.3 mg of sacubitril and 25.7 mg of valsartan (as sacubitril valsartan sodium complex).
o Each 49 mg/51 mg film-coated tablet contains 48.6 mg of sacubitril and 51.4 mg of valsartan (as sacubitril valsartan sodium complex).
o Each 97 mg/103 mg film-coated tablet contains 97.2 mg of sacubitril and 102.8 mg of valsartan (as sacubitril valsartan sodium complex).
The other components of the tablet core are microcrystalline cellulose, low-substituted hydroxypropyl cellulose, crospovidone, magnesium stearate, talc, and anhydrous colloidal silica (see end of section 2 under “Entresto contains sodium”).
The coating of the 24 mg/26 mg and 97 mg/103 mg tablets contains 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).

Description of the appearance of Entresto and contents of the pack
Entresto 24 mg/26 mg film-coated tablets are oval-shaped, violet-white tablets, marked “NVR” on one side and “LZ” on the other. Approximate tablet dimensions: 13.1 mm x 5.2 mm.
Entresto 49 mg/51 mg film-coated tablets are oval-shaped, light yellow tablets, marked “NVR” on one side and “L1” on the other. Approximate tablet dimensions: 13.1 mm x 5.2 mm.
Entresto 97 mg/103 mg film-coated tablets are oval-shaped, light pink tablets, marked “NVR” on one side and “L11” on the other. Approximate tablet dimensions: 15.1 mm x 6.0 mm.
The tablets are supplied in packs containing 14, 20, 28, 56, 168 or 196 tablets, and in multiple packs of 7 boxes each containing 28 tablets. The 49 mg/51 mg and 97 mg/103 mg tablets are also supplied in multiple packs comprising 3 boxes, each containing 56 tablets.
Not all pack sizes may be marketed.

Marketing Authorization 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 Nuremberg
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf.: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 111

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

Package leaflet: information for the user

Entresto 6 mg/6 mg granules in open capsules, 15 mg/16 mg granules in open capsules

sacubitril/valsartan
Please read this leaflet carefully before you (or your child) take this medicine
because it contains important information for you.

Keep this leaflet. 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 (or your child) only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you (or your child) experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Entresto is and what it is used for
What you need to know before taking Entresto
How to take Entresto
Possible side effects
How to store Entresto
Contents of the pack and other information

1. What Entresto is and what it is used for

Entresto is a heart medicine containing a neprilysin and angiotensin receptor inhibitor. It releases two active substances, sacubitril and valsartan.
Entresto is used to treat a type of long-term heart failure in 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, weakness, fatigue, and swelling of the ankles.

2. What you should know before you (or your child) take Entresto

Do not take Entresto:

if you (or your child) are allergic to sacubitril, valsartan, or any of the other ingredients of this medicine (listed in section 6).
if you (or your child) are taking another type of medicine called an angiotensin-converting enzyme (ACE) inhibitor (for example enalapril, lisinopril, or ramipril), which is used to treat high blood pressure or heart failure. If you are taking an ACE inhibitor, wait 36 hours after taking the last dose before starting Entresto (see "Other medicines and Entresto").
if you (or your child) 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 of the throat blocks the airways) while taking an ACE inhibitor or an angiotensin receptor blocker (ARB) (such as valsartan, telmisartan, or irbesartan).
if you (or your child) have a history of angioedema that is hereditary or of unknown cause (idiopathic).
if you (or your child) 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 (or your child) have severe liver disease.
if you (or your daughter) are more than 3 months pregnant (see "Pregnancy and breastfeeding"). If any of these apply to you, do not take Entresto and consult your doctor.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before or while taking Entresto

if you (or your child) are being treated with an angiotensin receptor blocker (ARB) or aliskiren (see "Do not take Entresto").
if you (or your child) have ever had angioedema (see "Do not take Entresto" and section 4 "Possible side effects").
if after taking Entresto you experience abdominal pain, nausea, vomiting, or diarrhoea. Your doctor will decide whether treatment should continue. Do not stop taking Entresto on your own.
if you (or your child) have low blood pressure or are taking any other medicine to lower blood pressure (for example, a medicine that increases urine production (a diuretic)), or if you have vomiting or diarrhoea, especially if you are 65 years of age or older or have kidney disease and low blood pressure.
if you (or your child) have kidney disease.
if you (or your child) are dehydrated.
if you (or your child) have narrowing of a renal artery.
if you (or your child) have liver disease.
if you (or your child) experience hallucinations, paranoia, or changes in sleep patterns while taking Entresto.
if you (or your child) have hyperkalaemia (high levels of potassium in the blood).
if you (or your child) suffer from heart failure classified as NYHA class IV (unable to perform any physical activity without discomfort and may experience symptoms even at rest).

If any of these apply to you, inform your doctor, pharmacist, or nurse before taking Entresto.
Your doctor may check your blood potassium and sodium levels regularly during treatment with Entresto. In addition, your doctor may monitor your blood pressure at the start of treatment and when doses are increased.

Children (under one year of age)
Use in children under one year of age is not recommended. Experience with use in this age group is limited. Film-coated tablets of Entresto are available for children weighing more than 40 kg.

Other medicines and Entresto
Tell your doctor, pharmacist, or nurse if you (or your child) are taking, have recently taken, or might take any other medicines. It may be necessary to adjust the dose, take additional precautions, or even stop taking one of these medicines. This is particularly important for the following medicines:

ACE inhibitors. Do not take Entresto with ACE inhibitors. If you are being treated with an ACE inhibitor, wait 36 hours after taking the last dose of the ACE inhibitor before starting Entresto (see "Do not take Entresto"). If you stop taking Entresto, wait 36 hours after taking the last dose of Entresto before starting an ACE inhibitor.
other medicines used to treat heart failure or lower blood pressure, such as angiotensin receptor blockers or aliskiren (see "Do not take Entresto").
certain medicines known as statins, used to lower high cholesterol levels (e.g. atorvastatin).
sildenafil, tadalafil, vardenafil, or avanafil, medicines used to treat erectile dysfunction or pulmonary hypertension.
medicines that increase potassium levels in the blood. These include potassium supplements, potassium-containing salt substitutes, potassium-sparing medicines, and heparin.
painkillers of the type known as non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors. If you are taking one of these, your doctor may want to monitor kidney function when starting or adjusting treatment (see "Warnings and precautions").
lithium, a medicine used to treat certain psychiatric conditions.
furosemide, a medicine belonging to the diuretic class, used to increase urine production.
nitroglycerin, a medicine used to treat angina pectoris.
certain types of antibiotics (rifamycin group), ciclosporin (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 any of these apply to you, inform your doctor or pharmacist before taking Entresto.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
You must inform your doctor if you (or your daughter) think you may be pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking this medicine before becoming pregnant or as soon as you find out you are pregnant, and will recommend 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 the unborn child if taken after the third month of pregnancy.

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

Driving and using machines
Before driving a vehicle, operating tools or machinery, or performing other activities requiring concentration, you should be aware of how you react to Entresto. If you experience dizziness or feel very tired while taking this medicine, do not drive, ride a bicycle, or operate tools or machinery.

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

3. How to take Entresto

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Your doctor (or your child's doctor) will decide the starting dose based on body weight and
other factors, including medicines previously taken. The doctor will adjust the dose every 2–4 weeks
until the optimal dose is reached.
Entresto must be given twice daily (once in the morning and once in the evening).
See the instructions for use on how to prepare and take Entresto granules.
Patients treated with Entresto may develop low blood pressure (dizziness, feeling of emptiness in the head),
high levels of potassium in the blood (detected when the doctor performs a blood test), or reduced kidney function.
If this occurs, the doctor may reduce the dose of any medicine you (or your child) are taking, temporarily reduce
the dose of Entresto, or completely discontinue treatment with Entresto.
If you take more Entresto than you should
If you (or your child) have accidentally taken too many Entresto granules, or if someone else has taken your granules,
contact your doctor immediately. If you (or your child) experience severe dizziness and/or fainting, inform your doctor as soon as possible and lie down.
If you (or your child) forget to take Entresto
It is recommended to take the medicine at the same time every day. However, if you (or your child) forget to take a dose,
simply take the next dose at the scheduled time. Do not take a double dose to make up for the forgotten dose.
If you (or your child) stop taking Entresto
Stopping treatment with Entresto may cause your condition to worsen. Do not stop taking this medicine unless instructed by your doctor.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Some side effects may be serious.

Stop taking Entresto and seek immediate medical help if you (or your child) notice any swelling of the face, lips, tongue and/or throat, which may cause difficulty breathing or swallowing. These may 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 worsen, inform your doctor or pharmacist.
Very common (may affect more than 1 in 10 people)

low blood pressure which may cause dizziness and a feeling of emptiness in the head (hypotension)
high levels of potassium in the blood, shown by a blood test (hyperkalaemia)
reduced kidney function (renal impairment)

Common (may affect up to 1 in 10 people)

cough
dizziness
diarrhoea
low levels of red blood cells in the blood, shown by a blood test (anaemia)
tiredness (fatigue)
sudden inability of the kidney to work properly (renal failure)
low levels of potassium in the blood, shown by a blood test (hypokalaemia)
headache
fainting (syncope)
weakness (asthenia)
feeling unwell (nausea)
low blood pressure (dizziness, feeling of emptiness in the head) when moving from a sitting or lying position to a standing position
gastritis (stomach pain, nausea)
sensation of dizziness (vertigo)
low levels of sugar in the blood, shown by a blood test (hypoglycaemia)

Uncommon (may affect up to 1 in 100 people)

allergic reaction with skin rash and itching (hypersensitivity)
dizziness when moving from a sitting to a standing position (postural dizziness)
low levels of sodium in the blood, shown by a blood test (hyponatraemia)

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

seeing, hearing or sensing things that are not there (hallucinations)
changes in the way of sleeping (sleep disorders)

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

paranoia
intestinal angioedema: swelling in the intestine presenting with symptoms such as abdominal pain, nausea, vomiting and diarrhoea

Not known (frequency cannot be estimated from the available data)

sudden involuntary muscle twitch (myoclonus)

Reporting of side effects
If you (or your child) experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Entresto

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature conditions.
Store in the original packaging to protect the medicine from moisture.
Do not use this medicine if the packaging is damaged or shows signs of tampering.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Entresto contains

The active substances are sacubitril and valsartan.
- Entresto 6 mg/6 mg granules in open capsules (granules in capsule) contains four granules equivalent to 6.1 mg of sacubitril and 6.4 mg of valsartan (as sacubitril valsartan sodium salt complex).
- Entresto 15 mg/16 mg granules in open capsules (granules in capsule) contains ten granules corresponding to 15.18 mg of sacubitril and 16.07 mg of valsartan (as sacubitril valsartan sodium salt complex).
The other ingredients of the granules are: microcrystalline cellulose, hydroxypropylcellulose, magnesium stearate, anhydrous colloidal silica and talc.
The ingredients of the film coating are: basic butylated methacrylate copolymer, talc, stearic acid and sodium lauryl sulfate (see the end of section 2 under “Entresto contains sodium”).
The ingredients of the capsule shell are: hypromellose, titanium dioxide (E171), iron oxide (yellow) (E172) (only in Entresto 15 mg/16 mg) and printing ink.
- The ingredients of the printing ink are: shellac, propylene glycol, iron oxide (red) (E172), ammonia solution (concentrated) and potassium hydroxide.

Description of the appearance of Entresto and contents of the pack
Entresto 6 mg/6 mg granules are white to slightly yellowish, round-shaped granules with a diameter of approximately 2 mm, supplied in a capsule. The capsule consists of a white cap marked with “04” in red and a transparent body marked with “NVR” in red. An arrow is printed on both the body and the cap.
Entresto 15 mg/16 mg granules are white to slightly yellowish, round-shaped granules with a diameter of approximately 2 mm, supplied in a capsule. The capsule consists of a yellow cap marked with “10” in red and a transparent body marked with “NVR” in red. An arrow is printed on both the body and the cap.
Entresto 6 mg/6 mg granules in open capsules and Entresto 15 mg/16 mg granules in open capsules are supplied in packs containing 60 capsules.

Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Lek farmacevtska družba d.d.
Verovskova Ulica 57
1526 Ljubljana
Slovenia
Novartis Pharmaceutical Manufacturing LLC
Verovskova Ulica 57
1000 Ljubljana
Slovenia
Novartis Pharma GmbH
Roonstrasse 25
90429 Nuremberg
Germany
Novartis Farmaceutica S.A.
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder: