Valkubit

Package leaflet: Information for the patient

Valkubit, 24 mg + 26 mg, film-coated tablets
Valkubit, 49 mg + 51 mg, film-coated tablets
Valkubit, 97 mg + 103 mg, film-coated tablets
Sacubitrilum + Valsartanum
Please read this leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Valkubit is and what it is used for

Valkubit is a heart medicine containing an angiotensin receptor blocker and a neprilysin inhibitor. It provides two active substances, sacubitril and valsartan, to the body.
Valkubit is used to treat a certain type of chronic heart failure in adults, children and adolescents (aged one year and older).
This type of heart failure occurs when the heart is too weak to pump enough blood to the lungs and other parts of the body. The most common symptoms of heart failure are: shortness of breath, feeling tired, fatigue, and swelling around the ankles.

2. Important information before using Valkubit

When not to use Valkubit

• if the patient is allergic (hypersensitive) to sacubitril, valsartan, or any of the other ingredients of this medicine (listed in section 6);
• if the patient is taking another medicine called an angiotensin-converting enzyme (ACE) inhibitor (e.g. enalapril, lisinopril or ramipril), which is used to treat high blood pressure or heart failure. If the patient has been taking an ACE inhibitor, they must wait 36 hours after taking the last dose of the ACE inhibitor before starting treatment with Valkubit (see section "Valkubit with other medicines");
• if the patient has ever had a reaction called angioedema (rapid swelling of the subcutaneous tissues in areas such as the face, throat, arms and legs, which may be life-threatening if swelling of the throat causes airway obstruction) after taking an ACE inhibitor or an angiotensin receptor blocker (ARB) (e.g. valsartan, telmisartan or irbesartan);
• if the patient has previously experienced angioedema that is hereditary or of unknown cause (idiopathic angioedema);
• if the patient has diabetes or kidney problems and is currently being treated with a blood pressure-lowering medicine containing aliskiren (see section "Valkubit with other medicines");
• if the patient has severe liver disease;
• if the patient is more than 3 months pregnant (see section "Pregnancy and breastfeeding"). If any of these situations apply to the patient, do not take Valkubit and consult a doctor.

Warnings and precautions
Before starting and while taking Valkubit, discuss with your doctor, pharmacist,
or nurse:

• if the patient is currently being treated with an angiotensin receptor blocker (ARB) or aliskiren (see section "When not to use Valkubit");
• if the patient has ever had angioedema (see section "When not to use Valkubit" and section 4 "Possible side effects");
• if the patient experiences abdominal pain, nausea, vomiting, or diarrhoea after taking Valkubit. The doctor will decide whether treatment should continue. Do not make your own decision to stop taking Valkubit;
• if the patient has low blood pressure or is taking other medicines that lower blood pressure (e.g. a diuretic, which increases urine production), or if the patient is experiencing vomiting or diarrhoea, especially if the patient is 65 years of age or older, or if the patient has kidney disease and low blood pressure;
• if the patient has kidney disease;
• if the patient is dehydrated;
• if there is renal artery stenosis;
• if the patient has liver disease;
• if the patient experiences hallucinations, paranoia, or changes in sleep patterns while taking Valkubit;
• if the patient has hyperkalaemia (high potassium levels in the blood);
• if the patient has heart failure classified as NYHA Class IV (inability to carry out any physical activity without discomfort and possible presence of symptoms even at rest).

If any of these situations apply to the patient, talk to a doctor,
pharmacist, or nurse before taking Valkubit.
While being treated with Valkubit, the doctor may regularly check the patient's blood potassium and sodium levels. In addition, the doctor may monitor the patient's blood pressure at the start of treatment and when increasing the dose.
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. This medicine is not suitable for children aged 1 year and older who weigh less than 40 kg, as it may not be possible to administer the appropriate dose using Valkubit tablets. The doctor or pharmacist should check whether alternative formulations (e.g. granules) are available to ensure an appropriate dose.
Valkubit with other medicines
Tell your doctor, pharmacist, or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. It may be necessary to adjust the dose, take additional precautions, or even discontinue one of the medicines. This is particularly important for the following medicines:

• ACE inhibitors. Do not take Valkubit with ACE inhibitors. If the patient is taking an ACE inhibitor, they must wait 36 hours after taking the last dose of the ACE inhibitor before starting treatment with Valkubit (see section "When not to use Valkubit"). If treatment with Valkubit is discontinued, the patient must wait 36 hours after taking the last dose of Valkubit before starting treatment with an ACE inhibitor;
• other medicines used to treat heart failure or lower blood pressure, such as angiotensin receptor blockers or aliskiren (see "When not to use Valkubit");
• certain medicines called statins, used to lower high cholesterol levels (e.g. atorvastatin);
• sildenafil, tadalafil, vardenafil, or avanafil, which are 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 belonging to a group called non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors. If the patient is taking one of these medicines, the doctor may recommend monitoring kidney function at the start of treatment or when changing the dose (see "Warnings and precautions");
• lithium, a medicine used to treat certain types of mental illness;
• furosemide, a medicine belonging to a group called diuretics, used to increase urine production;
• nitroglycerin, a medicine used to treat angina pectoris;
• certain antibiotics (rifamycin group), cyclosporine (used to prevent rejection of transplanted organs), or antiviral medicines such as ritonavir (used in the treatment of HIV/AIDS);
• metformin, a medicine used to treat diabetes. If any of the above apply to the patient, inform the doctor or pharmacist before taking Valkubit.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
If the patient believes she is (or suspects she might be) pregnant, she must inform her doctor. The doctor will usually advise women to stop taking this medicine before becoming pregnant or as soon as pregnancy is confirmed and will prescribe an alternative to Valkubit.
This medicine is not recommended for use during early pregnancy and must not be taken after 3 months of pregnancy, as it may seriously harm the unborn child if used after the third month of pregnancy.
Breastfeeding
Use of Valkubit is not recommended for breastfeeding mothers. Inform the doctor if the patient is breastfeeding or intends to start breastfeeding.
Driving and operating machinery
Before driving, operating tools or machinery, or performing tasks requiring concentration, the patient should ensure how Valkubit affects them. If the patient experiences dizziness or fatigue while taking this medicine, they should not drive, ride a bicycle, or use tools and machinery.
Valkubit contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".

3. How to take Valkubit

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.

Adults
Treatment usually starts with one tablet of 24 mg + 26 mg or 49 mg + 51 mg twice daily (one tablet in the morning and one tablet in the evening). The doctor will determine the exact starting dose for the patient, taking into account previously used medications and the patient's blood pressure. The doctor will then adjust the dose every 2–4 weeks depending on the response to treatment, until the optimal dose for the patient is established.
The usual recommended target dose is 97 mg + 103 mg twice daily (one tablet in the morning and one tablet in the evening).

Children and adolescents (aged one year and older)
The patient's doctor (or the child's doctor) will determine the initial dose based on body weight and other factors, including previously used medications. The doctor will adjust the dose every 2–4 weeks until the optimal dose is established.
Valkubit should be administered twice daily (one tablet in the morning and one tablet in the evening).
Valkubit coated tablets are not intended for use in children weighing less than 40 kg. For these patients, the doctor or pharmacist will check whether alternative formulations of the medicine (e.g. granules) are available.

Patients taking Valkubit may experience low blood pressure (dizziness, feeling of emptiness in the head), high potassium levels in the blood (which can be detected in blood tests ordered by a doctor), or worsening kidney function. If this occurs, the doctor may reduce the dose of one of the other medications the patient is taking, temporarily reduce the dose of Valkubit, or permanently discontinue treatment with Valkubit.

The tablets should be swallowed with a glass of water. Valkubit can be taken with or without food. It is not recommended to divide or crush the tablets. Valkubit tablets are film-coated to protect them from external conditions and to facilitate swallowing. The tablet coating is not suitable for crushing.

Taking more Valkubit than recommended
If a patient accidentally takes too many Valkubit tablets, or if someone else takes these tablets, contact a doctor immediately. If severe dizziness and/or fainting occur, contact a doctor as soon as possible and the patient should lie down.

Missing a dose of Valkubit
It is recommended to take the medicine at the same time each day. However, if a patient forgets to take a dose, simply take the next dose at the scheduled time. Do not take a double dose to make up for a missed dose.

Stopping Valkubit
Stopping treatment with Valkubit may worsen the patient's condition. Do not stop taking the medicine unless instructed to do so by a doctor.

If there are any further doubts concerning the use of this medicine, consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects may be serious.
You must stop taking Valkubit and seek medical help immediately if you notice
any swelling of the face, lips, tongue and (or) throat, which may cause
difficulty in breathing or swallowing. These may be symptoms of angioedema (an uncommon
side effect that may occur in up to 1 in 100 people).
Other possible side effects:
If any of the symptoms listed below get worse, tell your doctor
or pharmacist.
Very common (may affect more than 1 in 10 people)

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

Common (may affect up to 1 in 10 people)

• cough
• dizziness
• diarrhoea
• low number of red blood cells, detected in blood tests (anaemia)
• fatigue
• (acute) inability of the kidneys to function properly (renal failure)
• low potassium levels in the blood, detected in blood tests (hypokalaemia)
• headache
• fainting
• weakness
• nausea
• low blood pressure (dizziness, lightheadedness) when changing position from sitting or lying down to standing up
• inflammation of the stomach (abdominal pain, nausea)
• sensation of spinning (dizziness)
• low blood sugar levels, detected in blood tests (hypoglycaemia)

Uncommon (may affect up to 1 in 100 people)

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

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

• seeing, hearing or feeling things that are not there (hallucinations)
• changes in sleep cycle (sleep disturbances)

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

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

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

• sudden, involuntary, jerking muscle contractions (myoclonus)

Reporting of side effects
If you experience any side effects, including any not listed
in this leaflet, tell your doctor, pharmacist or nurse. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Valkubit

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the outer carton
after the word "EXP". The expiry date refers to the last day of the stated month.
There are no special storage temperature requirements for this medicine.
Store in the original packaging to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. Such measures will help
protect the environment.

6. Contents of the pack and other information

What Valkubit contains

• The active substances in this medicine are sacubitril and valsartan.

Valkubit, 24 mg + 26 mg, film-coated tablets
Each film-coated tablet contains sodium sacubitril equivalent to 24.3 mg of sacubitril and
valsartan disodium equivalent to 25.7 mg of valsartan.
Valkubit, 49 mg + 51 mg, film-coated tablets
Each film-coated tablet contains sodium sacubitril equivalent to 48.6 mg of sacubitril and
valsartan disodium equivalent to 51.4 mg of valsartan.
Valkubit, 97 mg + 103 mg, film-coated tablets
Each film-coated tablet contains sodium sacubitril equivalent to 97.2 mg of sacubitril and
valsartan disodium equivalent to 102.8 mg of valsartan.

• Other ingredients in the tablet core: povidone, microcrystalline cellulose, talc, crospovidone, anhydrous colloidal silica, magnesium stearate.
• Other ingredients in the tablet coating and film coat: polyvinyl alcohol, calcium carbonate, macrogol, talc, red iron oxide (E 172) [only for doses 24 mg + 26 mg and 97 mg + 103 mg], black iron oxide (E 172) [only for dose 24 mg + 26 mg], yellow iron oxide (E 172) [only for dose 49 mg + 51 mg]. See section 2 "Valkubit contains sodium".

What Valkubit looks like and contents of the pack
Valkubit, 24 mg + 26 mg, film-coated tablets
Light grey-pink, round, biconvex, film-coated tablet with the marking S3 on one side.
Tablet dimensions: approximately 9 mm in diameter.
Valkubit, 49 mg + 51 mg, film-coated tablets
Yellow, round, biconvex, film-coated tablet with the marking S2 on one side.
Tablet dimensions: approximately 9 mm in diameter.
Valkubit, 97 mg + 103 mg, film-coated tablets
Orange-pink, oval, biconvex, film-coated tablet with the marking S1 on one side.
Tablet dimensions: 15 mm x 8 mm.

Valkubit is available in packs containing:

• 14, 20, 28, 30, 56, 60, 84, 90, 168, 196 and 200 film-coated tablets in blister packs, in a cardboard box.
• 14, 28, 56, 84, 168 and 196 film-coated tablets in calendar blister packs, in a cardboard box.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
tel. 22 57 37 500