Culbista

Package leaflet: Information for the patient

Culbista, 24 mg + 26 mg, film-coated tablets
Culbista, 49 mg + 51 mg, film-coated tablets
Culbista, 97 mg + 103 mg, film-coated tablets
sacubitril + valsartan
Please read the entire 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 questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Culbista is and what it is used for

Culbista is a heart medication containing an angiotensin receptor blocker and a neprilysin inhibitor.
It delivers two active substances, sacubitril and valsartan, into the body.
Culbista is used in the treatment of a certain type of chronic heart failure in adults.
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 taking Culbista

When not to take Culbista:

• if the patient is allergic 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), 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 Culbista (see section "Culbista with other medicines");
• if the patient has ever had a reaction called angioedema (rapid swelling under the skin in areas such as the face, throat, arms and legs, which may be life-threatening if swelling of the throat blocks the airways) after taking an ACE inhibitor or an angiotensin receptor blocker (ARB) (e.g. valsartan, telmisartan or irbesartan);
• if the patient has had angioedema that is hereditary or of unknown cause (idiopathic);
• if the patient has diabetes or kidney problems and is currently being treated with a blood pressure-lowering medicine containing aliskiren (see section "Culbista 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 Culbista and discuss this with the doctor.

Warnings and precautions

Before starting to take Culbista, talk to your doctor, pharmacist or nurse:

• if you are currently being treated with an angiotensin receptor blocker (ARB) or aliskiren (see section "When not to take Culbista");
• if you have ever had angioedema (see section "When not to take Culbista" and section 4 "Possible side effects");
• if you experience abdominal pain, nausea, vomiting or diarrhoea after taking Culbista. Your doctor will decide whether to continue treatment. Do not stop taking Culbista on your own;
• if you have low blood pressure or are taking any other medicines that lower blood pressure (e.g. a diuretic), or if you are experiencing 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 dehydrated;
• if you have renal artery stenosis;
• if you have liver disease;
• if you develop hallucinations, paranoia or changes in sleep patterns while taking Culbista;
• if you have hyperkalaemia (high potassium levels in the blood);
• if you have heart failure classified as NYHA Class IV (unable to carry out any physical activity without discomfort, and symptoms may occur even at rest).

If any of the above situations apply to you, inform your doctor, pharmacist or nurse before taking Culbista.

While being treated with Culbista, your doctor may regularly check your blood potassium and sodium levels. Your doctor may also measure your blood pressure at the beginning of treatment and when increasing the dose.

Children and adolescents

Other medicines containing sacubitril + valsartan should be used in children and adolescents.

Culbista with other medicines

Tell your doctor, pharmacist or nurse about any medicines you are currently taking, have recently taken or might take in the future. 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 Culbista with ACE inhibitors. If you are taking an ACE inhibitor, you must wait 36 hours after taking the last dose of the ACE inhibitor before starting treatment with Culbista (see section "When not to take Culbista"). If you stop taking Culbista, you must wait 36 hours after the last dose of Culbista 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 section "When not to take Culbista");
• certain medicines called statins, used to lower high cholesterol levels (e.g. atorvastatin);
• sildenafil, tadalafil, vardenafil or avanafil, medicines used to treat erectile dysfunction or pulmonary hypertension;
• medicines that increase potassium levels in the blood. These include potassium supplements, potassium-containing salt substitutes, potassium-sparing medicines and heparin;
• painkillers belonging to a group called non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors. If you are taking one of these medicines, your doctor may recommend monitoring kidney function when starting treatment or changing the dose (see section "Warnings and precautions");
• lithium, a medicine used to treat certain psychiatric disorders;
• furosemide, a medicine belonging to a group called diuretics, used to increase urine production;
• nitroglycerin, a medicine used to treat angina;
• certain antibiotics (such as rifampicin), 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 you, tell your doctor or pharmacist before taking Culbista.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before taking this medicine.

Pregnancy

If you think you are (or suspect you might be) pregnant, you must inform your doctor. Your doctor will usually advise women to stop taking this medicine before becoming pregnant or as soon as pregnancy is diagnosed, and will prescribe an alternative to Culbista. This medicine is not recommended during early pregnancy and must not be taken after 3 months of pregnancy, as it may seriously harm the unborn child if used beyond the third month of pregnancy.

Breastfeeding

Culbista is not recommended for use in breastfeeding mothers. Inform your doctor if you are breastfeeding or plan to start breastfeeding.

Driving and using machines

Before driving, operating tools or machines, or performing activities requiring concentration, ensure you know how Culbista affects you. If you experience dizziness or fatigue while taking this medicine, do not drive, ride a bicycle, or use tools or machinery.

Culbista contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per coated tablet, meaning the medicine is considered "sodium-free".

3. How to take Culbista

This medicine should always be taken as directed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Adults
Treatment usually starts with a dose of 49 mg + 51 mg twice daily (one tablet in the morning and one tablet in the evening). Your doctor will determine the exact starting dose based on previously used medications and blood pressure. If your doctor recommends a starting dose different from 49 mg + 51 mg, other products containing sacubitril + valsartan should be used. Your doctor will then adjust the dose every 2–4 weeks, depending on your response to treatment, until the optimal dose for you 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)
Other products containing sacubitril + valsartan should be used in children and adolescents.
Patients taking Culbista may experience low blood pressure (dizziness, feeling faint), high potassium levels in the blood (detected in blood tests ordered by your doctor), or worsening kidney function. If this occurs, your doctor may reduce the dose of one of your other medications, temporarily reduce the dose of Culbista, or permanently discontinue treatment with Culbista.
Tablets should be swallowed with a glass of water. Culbista can be taken with or without food. Splitting or crushing the tablets is not recommended.
Taking more Culbista than prescribed
If you accidentally take more tablets than prescribed, or if someone else takes these tablets, contact your doctor immediately. If severe dizziness and/or fainting occur, contact your doctor as soon as possible and the patient should lie down.
Missing a dose of Culbista
It is recommended to take the medicine at the same time each 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 tablet.
Stopping Culbista treatment
Stopping treatment with Culbista may worsen your condition. Do not discontinue taking this medicine unless instructed to do so by your doctor.
If you have any further questions about the use of 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 may be serious.
Patients should stop taking Culbista and seek immediate medical help if they 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 which may occur in up to 1 in 100 people).
Other possible side effects:
If any of the symptoms listed below worsen, patients should inform their doctor or pharmacist.
Very common (may occur in more than 1 in 10 people):

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

Common (may occur in up to 1 in 10 people):

• cough
• dizziness
• diarrhoea
• low number of red blood cells, detected in blood tests (anaemia)
• fatigue
• (acute) kidney function impairment (renal failure)
• low potassium levels in the blood, detected in blood tests (hypokalaemia)
• headache
• fainting
• weakness
• nausea
• low blood pressure (dizziness, lightheadedness) upon changing position from sitting or lying to standing
• gastritis (abdominal pain, nausea)
• vertigo
• low blood sugar levels, detected in blood tests (hypoglycaemia)

Uncommon (may occur in up to 1 in 100 people):

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

Rare (may occur in up to 1 in 1,000 people):

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

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

• paranoia
• intestinal angioedema: intestinal swelling causing abdominal pain, nausea, vomiting and diarrhoea

Not known (frequency cannot be estimated from available data)

• sudden involuntary muscle jerks (clonic muscle spasms)

Reporting of side effects
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, patients should inform their 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.: 22 49-21-301, fax: 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 the medicine.

5. How to store Culbista

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 the stated month.
There are no special temperature storage requirements for this medicine. Store in the original
packaging to protect from moisture.
Do not use Culbista if the packaging is damaged or shows signs of tampering.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What Culbista contains

• The active substances in this medicine are sacubitril and valsartan.
  • Each 24 mg + 26 mg film-coated tablet contains sacubitril sodium and valsartan disodium, equivalent to 24.3 mg of sacubitril and 25.7 mg of valsartan.
  • Each 49 mg + 51 mg film-coated tablet contains sacubitril sodium and valsartan disodium, equivalent to 48.6 mg of sacubitril and 51.4 mg of valsartan.
  • Each 97 mg + 103 mg film-coated tablet contains sacubitril sodium and valsartan disodium, equivalent to 97.2 mg of sacubitril and 102.8 mg of valsartan.
• The other ingredients in the tablet core are: microcrystalline cellulose (type A), low-substituted hydroxypropyl cellulose, crospovidone type A and B, talc, colloidal anhydrous silica, and magnesium stearate.
• The coating of the 24 mg + 26 mg tablet contains polyvinyl alcohol – partially hydrolysed; titanium dioxide; macrogol 4000; and talc.
• The coating of the 49 mg + 51 mg tablet contains polyvinyl alcohol – partially hydrolysed; titanium dioxide; macrogol 4000; talc; iron oxide red (E172); and iron oxide yellow (E172).
• The coating of the 97 mg/103 mg tablet contains polyvinyl alcohol – partially hydrolysed; titanium dioxide; macrogol 4000; talc; iron oxide red (E172); and iron oxide yellow (E172).

What Culbista looks like and contents of the pack

Culbista 24 mg + 26 mg, film-coated tablets are white, biconvex, oval film-coated tablets, with "S7V" engraved on one side and "L1" on the other. Approximate tablet dimensions: 13 mm x 5 mm.

Culbista 49 mg + 51 mg, film-coated tablets are pink, biconvex, oval film-coated tablets, with "S7V" engraved on one side and "M2" on the other. Approximate tablet dimensions: 12 mm x 5 mm.

Culbista 97 mg + 103 mg, film-coated tablets are pink, biconvex, oval film-coated tablets, with "S7V" engraved on one side and "H3" on the other. Approximate tablet dimensions: 16 mm x 6 mm.

Culbista 24 mg + 26 mg, film-coated tablets
Available in blister packs in cardboard packaging containing 14, 20, 28, 56 or 196 film-coated tablets, and in multipacks consisting of 7 boxes, each containing 28 film-coated tablets.
Available in unit dose blisters in cardboard packaging containing 14 x 1, 20 x 1, 28 x 1, 56 x 1 or 196 x 1 film-coated tablets, and in multipacks consisting of 7 boxes, each containing 28 x 1 film-coated tablets.

Culbista 49 mg + 51 mg, film-coated tablets
Culbista 97 mg + 103 mg, film-coated tablets
Available in blister packs in cardboard packaging containing 14, 20, 28, 56, 168 or 196 film-coated tablets, and in multipacks consisting of 3 boxes, each containing 56 film-coated tablets, or 7 boxes, each containing 28 film-coated tablets.
Available in unit dose blisters in cardboard packaging containing 14 x 1, 20 x 1, 28 x 1, 56 x 1, 168 x 1 or 196 x 1 film-coated tablets, and in multipacks consisting of 3 boxes, each containing 56 x 1 film-coated tablets, or 7 boxes, each containing 28 x 1 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
STADA Arzneimittel AG
Stadastrasse 2-18
61118 Bad Vilbel
Germany

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

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Stada Pharm Sp. z o.o.
ul. Krakowiaków 44
02-255 Warsaw
Tel. +48 22 737 79 20

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

24 mg + 26 mg film-coated tablets
Croatia: Culbista 24 mg/26 mg filmom obložene tablete
Czech Republic: Culbista
Estonia: Culbista
Netherlands: Culbista
Lithuania: Culbista 24 mg/26 mg plėvele dengtos tabletės
Latvia: Culbista 24 mg/26 mg apvalkotās tabletes

49 mg + 51 mg film-coated tablets
Croatia: Culbista 49 mg/51 mg filmom obložene tablete
Czech Republic: Culbista
Estonia: Culbista
Netherlands: Culbista
Lithuania: Culbista 49 mg/51 mg plėvele dengtos tabletės
Latvia: Culbista 49 mg/51 mg apvalkotās tabletes

97 mg + 103 mg film-coated tablets
Croatia: Culbista 97 mg/103 mg filmom obložene tablete
Czech Republic: Culbista
Estonia: Culbista
Netherlands: Culbista
Lithuania: Culbista 97 mg/103 mg plėvele dengtos tabletės
Latvia: Culbista 97 mg/103 mg apvalkotās tabletes