ENTRESTO 24 mg/26 mg Фильм-Coated Таблетки

Содержание инструкции

1. Entresto 24 mg/26 mg film-coated tablets, 49 mg/51 mg film-coated tablets, 97 mg/103 mg film-coated tablets
   1. What is Entresto and what is it 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. Package contents and other information
2. Entresto 6 mg/6 mg granules in openable capsules, 15 mg/16 mg granules in openable capsules
   1. What is Entresto and what is it used for
   2. What you need to know before you (or your child) take Entresto
   3. How to take Entresto
   4. Possible side effects
   5. How to store Entresto
   6. Content of the pack and other information

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

sacubitril/valsartan

Read this leaflet carefully before you start taking this medicine as 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 pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What Entresto is and what it is used for
• 2. What you need to know before you take 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 is Entresto and what is it used for

Entresto is a heart medicine containing a neprilysin inhibitor and an angiotensin receptor blocker.
It releases two active ingredients, sacubitril and valsartan.
Entresto is used for the treatment of a type of long-term heart failure in adults,
children and adolescents (from one year onwards).
This type of heart failure occurs when the heart is weak and cannot pump
blood in sufficient quantity 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 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 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 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 have a history of angioedema that is hereditary or for which the cause is not known (idiopathic)
• if you have diabetes or impaired kidney function and are being treated with a medicine to lower your blood pressure containing aliskiren (see “Other medicines and Entresto”).
• if you have a severe liver disease.
• if you are pregnant for more than 3 months (see “Pregnancy and breastfeeding”). If any of these apply to you, do not take Entresto and tell 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 about continuing the treatment. Do not stop taking Entresto on your own.
• if you have low blood pressure or are taking any other medicine to reduce your blood pressure (for example a medicine that increases urine production (diuretic)) or suffer from vomiting or diarrhoea, especially if you are 65 years of age or older or if you have kidney disease and low blood pressure.
• if you have kidney disease.
• if you are suffering from dehydration.
• if you have a narrowing of a kidney artery.
• if you have liver disease.
• if you experience hallucinations, paranoia or changes in your sleep pattern while taking Entresto.
• If you have hyperkalaemia (high levels of potassium in your blood).
• If you suffer from heart failure classified as class NYHA IV (unable to carry out any physical activity without discomfort and may have symptoms even at rest).

If any of these apply to you, tell your doctor, pharmacist or nurse before
taking Entresto.
Your doctor may check your potassium and sodium levels in the blood at regular intervals during
treatment with Entresto. Also, your doctor may check your blood pressure at the beginning of
treatment and when the doses are increased.

Children and adolescents
Do not give this medicine to children under 1 year of age because it has not been studied
in this age group. For children one year of age and over with a body weight of less than 40 Kg, this
medicine will be given as granules (instead of tablets).

Other medicines and Entresto
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 these medicines. This is particularly
important for the following medicines:

• ACE inhibitors. Do not take Entresto with ACE inhibitors. If you are taking an ACE inhibitor, wait 36 hours after 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 the last dose of Entresto before starting to take an ACE inhibitor.
• other medicines used for the treatment of heart failure or to lower blood pressure, such as angiotensin receptor blockers or aliskiren (see “Do not take Entresto”).
• some medicines known as statins that are used to lower high cholesterol levels (for example atorvastatin).
• sildenafil, tadalafil, vardenafil or avanafil, which are medicines used for the treatment of erectile dysfunction or for pulmonary hypertension.
• medicines that increase the amount of potassium in the blood. These include potassium supplements, salt substitutes containing potassium, 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 check your kidney function when you start or adjust treatment (see “Warnings and precautions”).
• lithium, a medicine used to treat some types of mental illness.
• furosemide, a medicine belonging to the class of diuretics that are used to increase the amount of urine that is produced.
• nitroglycerin, a medicine used to treat angina pectoris.
• some types of antibiotics (rifamycin group), cyclosporine (used for the prevention of organ rejection after transplantation) or antivirals such as ritonavir (used for the treatment of HIV/AIDS).
• metformin, a medicine used for the treatment of diabetes. If any of these apply to you, tell your doctor or pharmacist before taking Entresto.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
You must tell your doctor if you think you may be pregnant (or if there is a possibility of becoming
pregnant). Usually your doctor will advise you to stop taking this
medicine before becoming pregnant or as soon as you find out you are pregnant and will advise you to take another medicine instead of Entresto.
This medicine is not recommended in early pregnancy and must not be taken if you are
pregnant for more than 3 months as it can cause serious harm to the baby if taken after the third
month of pregnancy.
Breastfeeding
Entresto is not recommended for mothers who are breastfeeding. Tell your doctor if you are breastfeeding or
if you are about to start breastfeeding.

Driving and using machines
Before driving a vehicle, using tools or machines or doing other activities that require
concentration, you should know how you react to Entresto. If you feel dizzy or very
tired while taking this medicine, do not drive vehicles, ride a bicycle or
use tools or machines.

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

3. How to take Entresto

Take this medicine exactly as your doctor or pharmacist has told you. If you have any doubts, ask your doctor or pharmacist.
Adults
You will usually start by taking 24 mg/26 mg or 49 mg/51 mg tablets twice a day (one tablet in the morning and one tablet in the evening). The doctor will decide the exact starting dose based on the medicines you were taking previously and your blood pressure. The doctor will then adjust the dose every 2-4 weeks depending on your response to treatment until the most suitable dose for you is found.
Usually the recommended optimal dose is 97 mg/103 mg twice a day (one tablet in the morning and one tablet in the evening).
Children and adolescents (from one year onwards)
Your doctor (or your child's doctor) will decide the starting dose based on body weight and other factors including medicines taken previously. Your doctor will adjust the dose every 2-4 weeks until the optimal dose is identified.
Entresto must be given twice a day (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 treated with Entresto may develop low blood pressure (dizziness, lightheadedness), a high level of potassium in the blood (which is detected when the doctor performs a blood test) or a decrease in kidney function. If this occurs, the doctor may reduce the dose of any medicine you are taking, temporarily reduce the dose of Entresto or completely stop treatment with Entresto.
Swallow the tablets with a glass of water. You can take Entresto with or without food. Dividing or crushing the tablets is not recommended.

If you take more Entresto than you should
If you have inadvertently 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 every day at the same time. However, if you forget to take a dose, you should simply take the next dose at the scheduled time. Do not take a double dose to make up for a missed dose.

If you stop taking Entresto
Stopping treatment with Entresto may worsen your condition. Do not stop taking the medicine unless you have been told to do so by your doctor.
If you have any doubts 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 everybody gets them.

Some side effects can be serious.

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

Other possible side effects:
If any of the side effects listed below gets worse, tell your doctor or
pharmacist.

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

• low blood pressure which can cause symptoms of dizziness and light-headedness (hypotension)
• high levels of potassium in the blood shown by a blood test (hyperkalaemia)
• decreased 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)
• inability (acute) 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 sick (nausea)
• low blood pressure (dizziness, light-headedness) when moving from a sitting or lying position to a standing position
• gastritis (stomach pain, nausea)
• feeling of spinning (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 an upright 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 feeling things that are not there (hallucinations)
• changes in the way you sleep (sleep disorders)

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

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

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not
listed in this leaflet. You can also report side effects directly through the national reporting system listed in
Appendix 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 contraction (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 which is stated on the box and on the blister after
EXP. The expiry date refers to the last day of that month.
This medicine does not require any particular storage temperature.
Store in the original package to protect the medicine from moisture.
Do not use this medicine if you notice that the package is damaged or shows signs of
tampering.
Do not dispose of any medicine in wastewater. Ask your pharmacist how to dispose of medicines that
you no longer use. This will help protect the environment.

6. Package contents and other information

What Entresto contains

• The active ingredients are sacubitril and valsartan. Each film-coated tablet containing 24 mg/26 mg contains 24.3 mg of sacubitril and 25.7 mg of valsartan (as sacubitril valsartan sodium complex). Each film-coated tablet containing 49 mg/51 mg contains 48.6 mg of sacubitril and 51.4 mg of valsartan (as sacubitril valsartan sodium complex). Each film-coated tablet containing 97 mg/103 mg 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 hydroxypropylcellulose, crospovidone, magnesium stearate, talc and anhydrous colloidal silica (see at the end of paragraph 2 under “Entresto contains sodium”).
• The tablet coating for 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 tablet coating for 49 mg/51 mg tablets contains hypromellose, titanium dioxide (E171), macrogol (4000), talc, red iron oxide (E172) and yellow iron oxide (E172).

Description of Entresto and package contents
Entresto 24 mg/26 mg film-coated tablets are oval-shaped tablets of white to lilac color imprinted with “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 tablets of pale yellow color imprinted with “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 tablets of light pink color imprinted with “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 multipacks of 7 boxes, each containing 28 tablets. The 49 mg/51 mg and 97 mg/103 mg tablets are also supplied in multipacks including 3 boxes, each containing 56 tablets.
Not all 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 Nuremberg
Germany
For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111

Magyarország
Novartis Hungária Kft.
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf.: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 111

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00

Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888

France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01

Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1

Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Altre fonti d’informazioni
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

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

sacubitril/valsartan

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 only for you (or your child). Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If you (or your child) get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What Entresto is and what it is used for
• 2. What you need to know before you (or your child) take 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 is Entresto and what is it used for

Entresto is a heart medicine containing a neprilysin inhibitor and an angiotensin receptor blocker.
It releases two active ingredients, sacubitril and valsartan.
Entresto is used for the treatment of a type of long-term heart failure in children
and adolescents (from one year of age onwards).
This type of heart failure occurs when the heart is weak and cannot pump
blood in sufficient quantity 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 need to 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 to take 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 for which the cause is unknown (idiopathic).
• if you (or your child) have diabetes or impaired kidney function and are being treated with a medicine to lower your blood pressure containing aliskiren (see “Other medicines and Entresto”).
• if you (or your child) have a severe liver disease.
• if you (or your daughter) are pregnant for more than 3 months (see “Pregnancy and breastfeeding”). If any of these applies to you, do not take Entresto and tell 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 with 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 about continuing the treatment. 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 your blood pressure (for example a medicine that increases urine production (diuretic)) or suffer from vomiting or diarrhoea, especially if you are 65 years or older or if you have kidney disease and low blood pressure.
• if you (or your child) have kidney disease.
• if you (or your child) are suffering from dehydration.
• if there is a narrowing of one of your (or your child’s) renal arteries.
• if you (or your child) have liver disease.
• if you (or your child) experience hallucinations, paranoia or changes in your sleep pattern 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 carry out any physical activity without discomfort and may have symptoms even at rest).

If any of these applies to you, tell your doctor, pharmacist or nurse before
taking Entresto.
Your doctor may check your potassium and sodium levels in the blood at regular intervals during
treatment with Entresto. In addition, your doctor may check your blood pressure at the beginning of
treatment and when the doses are increased.

Children (under one year of age)
Use in children under one year of age is not recommended. There is limited experience with use
in this age group. For children weighing more than 40 kg, film-coated tablets of Entresto are available.

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
change the dose, take other 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 ACE inhibitor before starting to take Entresto (see “Do not take Entresto”). If you stop taking Entresto, wait 36 hours after taking the 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 blockers or aliskiren (see “Do not take Entresto”).
• some medicines known as statins which are used to lower high cholesterol levels (for example 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. These include potassium supplements, salt substitutes containing potassium, 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 check your kidney function when starting or adjusting treatment (see “Warnings and precautions”).
• lithium, a medicine used to treat some types of mental illness.
• furosemide, a medicine belonging to the class of diuretics which are used to increase the amount of urine that is produced.
• nitroglycerin, a medicine used to treat angina pectoris.
• some 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 applies to you, tell your doctor or pharmacist before taking Entresto.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
You must tell your doctor if you (or your daughter) think you are pregnant (or if there is a
possibility of becoming pregnant). As a rule, your doctor will advise you to stop
taking this medicine before becoming pregnant or as soon as you find out you are pregnant and will advise you to take another medicine instead of Entresto.
This medicine is not recommended in early pregnancy and must not be taken if you are
pregnant for more than 3 months as it can cause serious harm to the baby if taken after the third
month of pregnancy.
Breastfeeding
Entresto is not recommended for mothers who are breastfeeding. Tell your doctor if you are breastfeeding or
are about to start breastfeeding.

Driving and using machines
Before driving a vehicle, using tools or machines or performing other activities that require
concentration, you should know how you react to Entresto. If you feel dizzy or very
tired while taking this medicine, do not drive a vehicle, ride a bicycle or
use tools or machines.

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

3. How to take Entresto

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Your doctor (or your child’s doctor) will decide the initial dose based on body weight and
other factors, including any medicines you have taken previously. The doctor will adjust the dose every 2-4 weeks
until the optimal dose is found.
Entresto must be taken twice a day (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 lightheadedness), a high level of potassium in the blood (which is detected when the doctor
performs a blood test) or a decrease in kidney function. If this occurs, the doctor
may reduce the dose of any medicine that you (or your child) are taking, temporarily reduce
the dose of Entresto or completely stop treatment with Entresto.

If you take more Entresto than you should
If you (or your child) have inadvertently 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 every day at the same time. However, if you (or your child) forget to take a dose, you should simply take the next dose at the scheduled time. Do not
take a double dose to make up for a missed dose.

If you (or your child) stop taking Entresto
Stopping treatment with Entresto may cause your condition to worsen. Do not
stop taking the medicine unless you have been told to do so by your doctor.
If you have any doubts 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 everybody gets them.

Some side effects can 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 can cause difficulty breathing or swallowing. These may be signs of angioedema (an uncommon side effect that can affect up to 1 in 100 people).

Other possible side effects:
If any of the side effects listed below gets worse, tell your doctor or
pharmacist.

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

• low blood pressure which can cause symptoms of dizziness and light-headedness (hypotension)
• high levels of potassium in the blood, detected by a blood test (hyperkalaemia)
• decreased 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 detected by a blood test (anaemia)
• tiredness (fatigue)
• inability (acute) of the kidney to work properly (renal failure)
• low levels of potassium in the blood, detected by a blood test (hypokalaemia)
• headache
• fainting (syncope)
• weakness (asthenia)
• feeling unwell (nausea)
• low blood pressure (dizziness, light-headedness) when moving from a sitting or lying position to a standing position
• gastritis (stomach pain, nausea)
• feeling of spinning (vertigo)
• low levels of sugar in the blood, detected 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 position to an upright position (postural dizziness)
• low levels of sodium in the blood detected by 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 the way you sleep (sleep disorders)

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

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

Not known(frequency cannot be estimated from available data)

• sudden involuntary muscle contraction (myoclonus)

Reporting of side effects
If you (or your child) get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly through 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. How to store 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 box and on the blister after
EXP. The expiry date refers to the last day of that month.
This medicine does not require any particular storage temperature.
Store in the original package to protect the medicine from moisture.
Do not use this medicine if you notice that the package is damaged or shows signs of
tampering.
Do not dispose of any medicine in wastewater. Ask your pharmacist how to dispose of medicines that
you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Entresto contains

• The active ingredients are sacubitril and valsartan. Entresto 6 mg/6 mg granules for oral suspension (granules in a capsule) contains four granules equivalent to 6.1 mg of sacubitril and 6.4 mg of valsartan (as sacubitril valsartan sodium complex salt). Entresto 15 mg/16 mg granules for oral suspension (granules in a capsule) contains ten granules corresponding to 15.18 mg of sacubitril and 16.07 mg of valsartan (as sacubitril valsartan sodium complex salt).
• 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 paragraph 2 under “Entresto contains sodium”).
• The ingredients of the capsule shell are: hypromellose, titanium dioxide (E171), iron oxide (yellow) (E172) (only 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
The granules of Entresto 6 mg/6 mg are white to slightly yellow in colour, round in shape and approximately 2 mm in diameter and are supplied in a capsule. The capsule consists of a white head, marked with “04” in red and a transparent body, marked with “NVR” in red. An arrow is printed on both the body and the head.
The granules of Entresto 15 mg/16 mg are white to slightly yellow in colour, round in shape and approximately 2 mm in diameter and are supplied in a capsule. The capsule consists of a yellow head, marked with “10” in red and a transparent body, marked with “NVR” in red. An arrow is printed on both the body and the head.
Entresto 6 mg/6 mg granules for oral suspension and Entresto 15 mg/16 mg granules for oral suspension 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 on this medicine, contact the local representative of the marketing authorisation holder:

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111

Magyarország
Novartis Hungária Kft.
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf.: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 111

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00

Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888

France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01

Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1

Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

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

Instructions for use of Entresto 6 mg/6 mg granules for oral suspension and Entresto 15 mg/16 mg granules for oral suspension
To ensure you use the Entresto granules correctly for your child, it is important to follow these instructions. Your doctor, pharmacist or nurse will show you how to do this. Ask one of them if you have any questions.
The Entresto granules are contained within capsules and are available in two strengths: 6 mg/6 mg granules and 15 mg/16 mg granules. The capsules are packaged in blisters. You may receive one or both strengths depending on the dose your child needs.
You can see the difference between the two strengths from the colour of the capsule head and the marking on it.

• The capsule containing the 6 mg/6 mg granules has a white head with the number 04 printed on it.
• The capsule containing the 15 mg/16 mg granules has a yellow head with the number 10 printed on it.

The capsules containing the Entresto granules must be opened before use.
DO NOT swallow the capsules whole. DO NOT swallow the empty capsule shells.
If you are using both strengths of Entresto granules, make sure to use the correct number of capsules of each strength as indicated by your doctor, pharmacist or nurse.

Step 1	a Wash and dry your hands
Step 2	Place the following items on a flat, clean surface: o A small bowl, cup or spoon with a small amount of soft food that your child likes. o Blister pack with the capsules containing the Entresto granules. o Check that you have the correct strength(s) of Entresto granules.

Step 3	Press on the blister to remove the capsule(s).	a c o
Step 4	To open the capsule: Hold the capsule upright (with the coloured head pointing upwards) so that the granules are at the bottom of the capsule. Hold the capsule over the soft food. Gently press on the middle of the capsule and pull lightly to separate the two ends of the capsule. Be careful not to spill the contents.	d e l F a r m
Step 5	a Empty all the granules from the capsule onto the food. Make sure you do not lose any granules. Repeat steps 4 and 5 if you need more than one capsule to reach the prescribed dose.
Step 6	a Give your child the food with the granules immediately, making sure your child eats it all. Make sure your child does not chew the granules to avoid taste changes.
Step 7 A	n Throw away the empty capsule shells. g

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE TERMS OF THE MARKETING AUTHORISATION
Scientific conclusions
In light of the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report (PSUR) for sacubitril/valsartan, the PRAC’s scientific conclusions are as follows:
In consideration of the available literature data on the excretion of sacubitril and valsartan in breast milk, the PRAC considers that the excretion of sacubitril in breast milk is at least a reasonable possibility.
In consideration of the available literature data on myoclonus, and spontaneous reports including in some cases with a close temporal relationship and a positive de-challenge, the PRAC considers that a causal relationship between sacubitril/valsartan and myoclonus is at least a reasonable possibility.
The PRAC concluded that the product information of the medicinal products containing sacubitril/valsartan should be updated accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the related overall conclusions and with the justification of the recommendation.

Justification for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on sacubitril/valsartan, the CHMP considers that the benefit-risk balance of the medicine containing sacubitril/valsartan remains unchanged, subject to the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation.