Neparvis

Package leaflet: Information for the patient

Neparvis 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 all of 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Neparvis is and what it is used for

Neparvis is a heart medicine containing a neprilysin inhibitor and an angiotensin receptor blocker. It releases two active substances, sacubitril and valsartan.
Nepar vis 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, lack of energy, tiredness, and swelling of the ankles.

2. What you need to know before taking Neparvis

Do not take Neparvis

• 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) used to treat high blood pressure or heart failure. If you are currently taking an ACE inhibitor, wait 36 hours after taking your last dose before starting Neparvis (see "Other medicines and Neparvis").
• 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 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 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 Neparvis").
• 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 Neparvis and consult your doctor.

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

• if you are being treated with an angiotensin receptor blocker (ARB) or aliskiren (see "Do not take Neparvis").
• if you have ever had angioedema (see "Do not take Neparvis" and section 4 "Possible side effects").
• if, after taking Neparvis, you experience abdominal pain, nausea, vomiting, or diarrhoea. Your doctor will decide whether treatment should continue. Do not stop taking Neparvis 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 Neparvis.
• 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 Neparvis.
Your doctor may check your blood potassium and sodium levels regularly during treatment with Neparvis. Additionally, 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 a body weight below 40 kg, this medicine will be given as granules (instead of tablets).

Other medicines and Neparvis
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to 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 Neparvis with ACE inhibitors. If you are being treated with an ACE inhibitor, wait 36 hours after taking your last dose of the ACE inhibitor before starting Neparvis (see "Do not take Neparvis"). If you stop taking Neparvis, wait 36 hours after your last dose of Neparvis 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 Neparvis").
• 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 want 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 Neparvis.

Pregnancy and breastfeeding
If you are pregnant, think you might 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 find out you are pregnant, and will recommend an alternative medicine to Neparvis.
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
Neparvis is not recommended for breastfeeding mothers. Inform your doctor if you are breastfeeding or planning to start breastfeeding.

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

Neparvis 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 Neparvis

Take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Adults
You will usually start by taking 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 according to your response to treatment, until the most suitable dose for you is found.
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 decide 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 has been identified.
Neparvis should be given twice daily (one tablet in the morning and one tablet in the evening).
Neparvis film-coated tablets are not intended for use in children weighing less than
40 kg. Granules of Neparvis are available for these patients.
Patients treated with Neparvis may develop low blood pressure (dizziness, feeling of emptiness in the head),
high potassium levels in the blood (detected when the doctor performs a blood test), or reduced kidney function. If this occurs, your doctor may reduce the dose of any medicine you are taking, temporarily reduce the dose of
Neparvis, or completely discontinue treatment with Neparvis.
Swallow the tablets with a glass of water. You may take Neparvis with or without food. Splitting or crushing the tablets is not recommended.
If you take more Neparvis than you should
If you have accidentally taken too many Neparvis 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 Neparvis
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 Neparvis
Stopping treatment with Neparvis may cause your condition to worsen. Do not stop taking the medicine unless instructed to do so 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 everybody gets them.
Some side effects can be serious.

• Stop taking Neparvis 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 which 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 which presents with symptoms such as abdominal pain, nausea, vomiting and diarrhoea

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via 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 Neparvis

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 pack 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 you no longer require. This will help protect the environment.

6. Package contents and other information

What Neparvis 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 hydroxypropylcellulose, crospovidone, magnesium stearate, talc and anhydrous colloidal silica (see at the end of section 2 under “Neparvis 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 Neparvis and contents of the pack
Neparvis 24 mg/26 mg film-coated tablets are oval-shaped, violet-white tablets, with “NVR” imprinted on one side and “LZ” on the other. Approximate tablet dimensions: 13.1 mm x 5.2 mm.
Neparvis 49 mg/51 mg film-coated tablets are oval-shaped, light yellow tablets, with “NVR” imprinted on one side and “L1” on the other. Approximate tablet dimensions: 13.1 mm x 5.2 mm.
Neparvis 97 mg/103 mg film-coated tablets are oval-shaped, light pink tablets, with “NVR” imprinted 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 or 56 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 available in multiple packs containing 3 boxes, each with 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 about 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. Servier Portugal - Especialidades Farmacêuticas, Lda.
Tél: +33 1 55 47 66 00 Tel: +351 21 3122 000

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

Neparvis 6 mg/6 mg granulate in capsules to be opened, 15 mg/16 mg granulate in capsules to be opened

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 for you (or your child) only. Do not give it to other people, even if they have the same symptoms as you, because it could 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:

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

1. What Neparvis is and what it is used for

Neparvis is a heart medicine containing a neprilysin inhibitor and an angiotensin receptor blocker. It releases two active substances, sacubitril and valsartan.
Neparvis is used for the long-term treatment of a type of 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 need to know before you (or your child) take Neparvis

Do not take Neparvis:

• if you (or your child) are allergic to sacubitril, valsartan or to 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 Neparvis (see “Other medicines and Neparvis”).
• 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) when 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 Neparvis”).
• 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 Neparvis and consult your doctor.

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

• if you (or your child) are being treated with an angiotensin receptor blocker (ARB) or aliskiren (see “Do not take Neparvis”).
• if you (or your child) have ever had angioedema (see “Do not take Neparvis” and section 4 “Possible side effects”).
• if after taking Neparvis you experience abdominal pain, nausea, vomiting or diarrhoea. Your doctor will decide whether treatment should continue. Do not stop taking Neparvis 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 (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 a 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 pattern while taking Neparvis.
• 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 experience symptoms even at rest). If any of these apply to you, inform your doctor, pharmacist or nurse before taking Neparvis.

Your doctor may check your blood potassium and sodium levels regularly during treatment with Neparvis. In addition, your doctor may monitor your blood pressure at the beginning of treatment and when 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. Film-coated tablets of Neparvis are available for children weighing more than 40 kg.
Other medicines and Neparvis
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 discontinue one of these medicines. This is particularly important for the following medicines:

• ACE inhibitors. Do not take Neparvis 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 Neparvis (see “Do not take Neparvis”). If you stop taking Neparvis, wait 36 hours after taking the last dose of Neparvis before starting 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 Neparvis”).
• 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 want to monitor 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 Neparvis.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant or breastfeeding, ask your doctor or pharmacist for advice 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 know you are pregnant and will recommend taking another medicine instead of Neparvis. 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
Neparvis is not recommended for breastfeeding mothers. Inform your doctor if you are breastfeeding or planning to breastfeed.
Driving and using machines
Before driving, operating tools or machinery, or performing other activities requiring concentration, make sure you know how you react to Neparvis. If you feel dizzy or very tired while taking this medicine, do not drive, ride a bicycle or operate tools or machinery.
Neparvis 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 Neparvis

Take this medicine exactly as instructed 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 any previous medications. The doctor will adjust the dose every 2-4 weeks until the optimal dose is found.
Neparvis must be taken twice daily (once in the morning and once in the evening).
See the instructions for use on how to prepare and take Neparvis granules.
Patients being treated with Neparvis may develop low blood pressure (dizziness, feeling of emptiness in the head), high potassium levels in the blood (detected during a blood test performed by the doctor), 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 Neparvis, or completely discontinue treatment with Neparvis.

If you take more Neparvis than you should
If you (or your child) have accidentally taken too many Neparvis 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 Neparvis
It is recommended to take the medicine at the same time each 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 missed dose.

If you (or your child) stop taking Neparvis
Stopping treatment with Neparvis may cause your condition to worsen. Do not stop taking the 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 everybody gets them.
Some side effects can be serious.

• Stop taking Neparvis 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 get worse, 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, detected 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, detected by a blood test (anaemia)
• tiredness (fatigue)
• acute kidney failure (sudden inability of the kidney to work properly)
• 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, feeling of emptiness in the head) when changing 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, 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 changing from a sitting to a standing 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 sensing things that are not there (hallucinations)
• changes in the way of sleeping (sleep disturbances)

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 listed in Annex V.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Neparvis

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 you notice that 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 Neparvis contains

• The active substances are sacubitril and valsartan.
  • Neparvis 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).
  • Neparvis 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 "Neparvis contains sodium").
• The ingredients of the capsule shell are: hypromellose, titanium dioxide (E171), iron oxide (yellow) (E172) (only in Neparvis 15 mg/16 mg), and printing ink.
  • The ingredients of the printing ink are: shellac, propylene glycol, iron oxide (red) (E172), concentrated ammonia solution, and potassium hydroxide.

Description of the appearance of Neparvis and contents of the pack
The granules of Neparvis 6 mg/6 mg are white to slightly yellow, round-shaped, approximately 2 mm in diameter, and 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.
The granules of Neparvis 15 mg/16 mg are white to slightly yellow, round-shaped, approximately 2 mm in diameter, and 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.
Neparvis 6 mg/6 mg granules in open capsules and Neparvis 15 mg/16 mg granules in open capsules are available 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 medicinal product, please contact the local representative of the Marketing Authorisation 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
Laboratorios Farmacéuticos ROVI, S.A. Novartis Poland Sp. z o.o.
Tel: +34 91 375 62 30 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Servier Portugal - Especialidades Farmacêuticas, Lda.
Tél: +33 1 55 47 66 00 Tel: +351 21 31299 01

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

Instructions for use of Neparvis 6 mg/6 mg granules in capsules to be opened and Neparvis

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

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

The capsules containing Neparvis 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 Neparvis granules, make sure you use the correct number of
capsules of each strength as instructed by your doctor, pharmacist, or nurse.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION
Scientific conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report (PSUR) for sacubitril/valsartan, the scientific conclusions of the PRAC are as follows:

In view of the available literature data on the excretion of sacubitril and valsartan in breast milk, the PRAC considers that excretion of sacubitril in breast milk is at least a reasonable possibility.

In view of the available literature data on myoclonus and spontaneous reports, which in some cases include 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 for medicinal products containing sacubitril/valsartan should be updated accordingly.

Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the respective general conclusions and the reasoning of the recommendation.

Reasons 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 medicinal product containing sacubitril/valsartan remains unchanged, subject to the proposed amendments to the product information.

The CHMP recommends the variation of the terms of the marketing authorisation.