Sacubitril and valsartan Accord

Patient Information Leaflet

Sacubitril and Valsartan Accord 24 mg/26 mg film-coated tablets, 49 mg/51 mg film-coated tablets, 97 mg/103 mg film-coated tablets

Equivalent medicinal product
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Sacubitril and valsartan Accord is and what it is used for

Sacubitril and valsartan Accord is a heart medicine containing a neprilysin inhibitor and an angiotensin receptor blocker. It releases two active substances, sacubitril and valsartan.
Sacubitril and valsartan/Accord is used for the long-term treatment of a type of heart failure in adults, children, and adolescents (aged one year and older).
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 taking Sacubitril and Valsartan Accord

Do not take Sacubitril and Valsartan Accord:

• 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 Sacubitril and Valsartan Accord (see "Other medicines and Sacubitril and Valsartan Accord").
• 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 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 Sacubitril and Valsartan Accord").
• 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 Sacubitril and Valsartan Accord and consult your doctor.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking or while taking Sacubitril and
Valsartan Accord:

• if you are being treated with an angiotensin receptor blocker (ARB) or aliskiren (see "Do not take Sacubitril and Valsartan Accord").
• if you have ever had angioedema (see "Do not take Sacubitril and Valsartan Accord" and section 4 "Possible side effects").
• if after taking Sacubitril and Valsartan Accord you experience abdominal pain, nausea, vomiting or diarrhoea. Your doctor will decide whether treatment should continue. Do not stop taking Sacubitril and Valsartan Accord 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 your sleep pattern while taking Sacubitril and Valsartan Accord.
• if you have hyperkalaemia (high levels of potassium in the blood).
• if you have heart failure classified as NYHA class IV (unable to carry out any physical activity without discomfort and may have symptoms even at rest). If any of these apply to you, inform your doctor, pharmacist or nurse before taking Sacubitril and Valsartan Accord. Your doctor may check your blood potassium and sodium levels at regular intervals during treatment with Sacubitril and Valsartan Accord. 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 Sacubitril and Valsartan Accord
Tell 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 stop taking one of these medicines. This is particularly important for the following medicines:

• ACE inhibitors. Do not take Sacubitril and Valsartan Accord 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 Sacubitril and Valsartan Accord (see "Do not take Sacubitril and Valsartan Accord"). If you stop taking Sacubitril and Valsartan Accord, wait 36 hours after taking the last dose of Sacubitril and Valsartan Accord 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 Sacubitril and Valsartan Accord").
• 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 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 Sacubitril and
Valsartan Accord.
Pregnancy and breastfeeding
If you are pregnant, think 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 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 another medicine instead of Sacubitril and Valsartan Accord.
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 baby if taken after the third month of pregnancy.
Breastfeeding
Sacubitril and Valsartan Accord 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, you should be aware of how you react to Sacubitril and Valsartan Accord. If you experience dizziness or feel very tired while taking this medicine, do not drive, ride a bicycle or operate tools or machinery.
Sacubitril and Valsartan Accord contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. essentially "sodium-free".

3. How to take Sacubitril and Valsartan Accord

Take this medicine exactly as your doctor or pharmacist has told you. If you have any doubts, consult your doctor or pharmacist.

Adults
You will usually start with 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 your dose every 2–4 weeks, depending on 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 1 year of age onwards)
Your doctor (or your child’s doctor) will decide the starting dose based on body weight and other factors, including previously taken medicines. The doctor will adjust the dose every 2–4 weeks until the optimal dose is identified.
Sacubitril and Valsartan Accord should be given twice daily (one tablet in the morning and one tablet in the evening).
Sacubitril and Valsartan Accord film-coated tablets are not intended for use in children weighing less than 40 kg. Granules of Sacubitril and Valsartan are available for these patients.

Patients treated with Sacubitril and Valsartan Accord may develop low blood pressure (dizziness, feeling of emptiness in the head), high potassium levels in the blood (detected during blood tests performed by your doctor), or reduced kidney function. If this occurs, your doctor may reduce the dose of any medicine you are taking, temporarily reduce the dose of Sacubitril and Valsartan Accord, or completely discontinue treatment with Sacubitril and Valsartan Accord.

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

If you take more Sacubitril and Valsartan Accord than you should
If you have accidentally taken too many Sacubitril and Valsartan Accord 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 Sacubitril and Valsartan Accord
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 Sacubitril and Valsartan Accord
Stopping treatment with Sacubitril and Valsartan Accord may worsen your condition. Do not stop taking this medicine unless instructed by your doctor.

If you have any questions about how to use 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 Sacubitril and Valsartan Accord and seek immediate medical help if you 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 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 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

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

• sudden involuntary muscle twitch (myoclonus)

Reporting of side effects
If you get any side effects, including any not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sacubitril and valsartan Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after
Exp. or 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 or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Sacubitril and valsartan Accord contains

• The active substances are sacubitril and valsartan.
  • Each 24 mg/26 mg film-coated tablet contains sodium sacubitril and disodium valsartan equivalent to 24.3 mg of sacubitril and 25.7 mg of valsartan.
  • Each 49 mg/51 mg film-coated tablet contains sodium sacubitril and disodium valsartan equivalent to 48.6 mg of sacubitril and 51.4 mg of valsartan.
  • Each 97 mg/103 mg film-coated tablet contains sodium sacubitril and disodium valsartan equivalent to 97.2 mg of sacubitril and 102.8 mg of valsartan.
• The other ingredients of the tablet core are microcrystalline cellulose; low-substituted hydroxypropylcellulose; crospovidone type A and B; talc; anhydrous colloidal silica; and magnesium stearate.
• The coating of the 24 mg/26 mg tablet contains poly(vinyl alcohol) - partially hydrolysed; titanium dioxide; macrogol; and talc.
• The coating of the 49 mg/51 mg tablet contains poly(vinyl alcohol) - partially hydrolysed; titanium dioxide; macrogol; talc; iron oxide red (E172); and iron oxide yellow (E172).
• The coating of the 97 mg/103 mg tablet contains poly(vinyl alcohol) - partially hydrolysed; titanium dioxide; macrogol; talc; red iron oxide (E172); and yellow iron oxide (E172).

Description of the appearance of Sacubitril and valsartan Accord and the contents of the pack
Sacubitril and valsartan Accord 24 mg/26 mg film-coated tablets (tablets) are white, biconvex, oval tablets with the imprint “S7V” on one side and “L1” on the other. Approximate tablet dimensions: 13 mm x 5 mm.
Sacubitril and valsartan Accord 49 mg/51 mg film-coated tablets: pink, biconvex, oval tablets with the imprint “S7V” on one side and “M2” on the other. Approximate tablet dimensions: 12 mm x 5 mm.
Sacubitril and valsartan Accord 97 mg/103 mg film-coated tablets are pink, biconvex, oval tablets with the imprint “S7V” on one side and “H3” on the other. Approximate tablet dimensions: 16 mm x 6 mm.

Sacubitril and valsartan Accord 24 mg/26 mg film-coated tablets
Sacubitril and valsartan Accord is available in blisters containing 20, 28, 50, 56 or 196 film-coated tablets, and in multiple packs containing 196 tablets (7 packs of 28) film-coated tablets.

Sacubitril and valsartan Accord 49 mg/51 mg film-coated tablets
Sacubitril and valsartan Accord is available in blisters containing 20, 28, 50, 56, 168 or 196 film-coated tablets, and in multiple packs containing 168 tablets (3 packs of 56) or 196 tablets (7 packs of 28) film-coated tablets.

Sacubitril and valsartan Accord 97 mg/103 mg film-coated tablets
Sacubitril and valsartan Accord is available in blisters containing 20, 56, 168 or 196 film-coated tablets, and in multiple packs containing 168 tablets (3 packs of 56) or 196 tablets (7 packs of 28) film-coated tablets.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est, 6a Planta,
08039 Barcelona,
Spain

Manufacturer
Synthon Hispania, S.L.,
Calle De Castello 1, Sant Boi De Llobregat,
Barcelona, 08830, Spain
Synthon B.V., Microweg 22,
6545 CM, Nijmegen
The Netherlands