Zali

Leaflet accompanying the packaging: patient information

Zali, 110 mg, hard capsules

Dabigatran etexilate

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including those not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Zali and what is it used for

Zali contains dabigatran etexilate as the active substance and belongs to a group of medicines called anticoagulants. Its action involves blocking a substance in the body responsible for blood clot formation.
Zali is used in adults to:

• prevent blood clots in the veins after hip or knee replacement surgery.
• prevent blood clots in the brain (stroke) and other blood vessels in the patient's body, if the patient has a type of irregular heartbeat called atrial fibrillation not caused by a heart valve problem and at least one additional risk factor.
• treat blood clots in the veins of the legs and lungs and prevent repeated blood clots in the veins of the legs and lungs.

Zali is used in children to:

• treat blood clots and prevent repeated blood clots.

2. Important information before taking Zali

When not to take Zali

• if the patient is allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6).
• if the patient has severe kidney impairment.
• if the patient is currently bleeding.
• if the patient has a disease of any internal organ that increases the risk of major bleeding (e.g. stomach ulcer, brain injury or bleeding into the brain, recent brain or eye surgery).
• if the patient has an increased tendency to bleed. This may be congenital, of unknown cause, or caused by the use of other medicines.
• if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, apixaban, or heparin), except when switching anticoagulant treatment, introducing a catheter into a vein or artery, when heparin is administered to the catheter to maintain its patency or when restoring normal heart function using a procedure called catheter ablation in atrial fibrillation.
• if the patient has severe liver impairment or liver disease that may lead to death.
• if the patient is taking oral ketoconazole or itraconazole, medicines used to treat fungal infections.
• if the patient is taking oral cyclosporine, a medicine used to prevent organ rejection.
• if the patient is taking dronedarone, a medicine used to treat heart rhythm disorders.
• if the patient is taking a combination medicine containing glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C.
• if the patient has been fitted with an artificial heart valve that requires ongoing anticoagulant treatment.

Warnings and precautions

Before starting Zali, discuss it with your doctor. If symptoms occurred during treatment with this medicine or the patient underwent surgery, consult a doctor.
The patient should inform the doctorif they have or have had any medical conditions or diseases, especially those listed below:

• if the patient has an increased risk of bleeding, such as:
• if the patient has recently experienced bleeding.
• if the patient has undergone surgical biopsy within the last month.
• if the patient has suffered a serious injury (e.g. bone fracture, head injury, or any injury requiring surgical treatment).
• if the patient has esophagitis or gastritis.
• if the patient has gastroesophageal reflux disease.
• if the patient is taking medicines that may increase the risk of bleeding. See below "Zali and other medicines".
• if the patient is taking anti-inflammatory medicines, such as diclofenac, ibuprofen, piroxicam.
• if the patient has an infection of the heart (bacterial endocarditis).
• if the patient has reduced kidney function or is dehydrated (feeling thirsty and producing a reduced amount of dark (concentrated)/foamy urine).
• if the patient is over 75 years old.
• if the patient is an adult and weighs 50 kg or less.
• only in the case of use in children: if the child has an infection around or in the brain.
• in the case of a heart attack or if the patient has been diagnosed with conditions

that increase the risk of a heart attack.

• if the patient has liver disease affecting blood test results. In such cases, the use of this medicine is not recommended.

When to exercise special caution when taking Zali

• if the patient needs to undergo surgery: In this case, it is necessary to discontinue Zali temporarily due to the increased risk of bleeding during and after surgery. It is very important to take Zali before and after surgery exactly as the doctor has instructed.
• if the surgical procedure requires the insertion of a catheter or injection into the spine (e.g. for epidural or spinal anesthesia or to reduce pain):
• It is very important to take Zali before and after surgery exactly as the doctor has instructed.
• The patient should immediately inform the doctor if they experience numbness or weakness in the lower limbs or problems with the intestines or bladder after the anesthesia has worn off, as urgent medical attention is required.
• if the patient has fallen or injured themselves during treatment, especially if they have injured their head. The patient should immediately seek medical attention. The doctor will examine the patient to determine if there is an increased risk of bleeding.
• if the patient has a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), the patient should inform the doctor, who will decide whether to change the treatment.

Zali and other medicines

Tell your doctor or pharmacist about all medicines the patient is taking, has recently taken, or might take. In
particular, tell your doctor before taking Zali if the patient is taking any of the following
medicines:

• Anticoagulant medicines (e.g. warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, aspirin).
• Medicines used to treat fungal infections (e.g. ketoconazole, itraconazole), unless these medicines are used only on the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking medicines containing amiodarone, quinidine, or verapamil, the doctor may recommend a lower dose of Zali, depending on the condition for which the medicine was prescribed. See also section 3.
• Medicines used to prevent organ rejection (e.g. tacrolimus, cyclosporine).
• A combination medicine containing glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C).
• Anti-inflammatory and pain-relieving medicines (e.g. aspirin, ibuprofen, diclofenac).
• St. John's Wort, a herbal medicine used to treat depression.
• Antidepressant medicines called selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors.
• Rifampicin or clarithromycin (both antibiotics).
• Antiviral medicines used to treat AIDS (e.g. ritonavir).
• Certain medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding

The effect of Zali on pregnancy and the unborn child is not known. This medicine should not be taken during pregnancy unless the doctor considers it safe. Women of childbearing age should avoid becoming pregnant while taking Zali.
Do not breastfeed while taking Zali.

Driving and using machines

Zali has no or negligible influence on the ability to drive and use machines.

Zali contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially 'sodium-free'.

3. How to take Zali

Zali capsules can be used in adults and children aged 8 years or older who can swallow the capsules whole. There are other age-appropriate formulations for the treatment of children under 8 years of age.
This medicine should always be taken exactly as the doctor has instructed. If in doubt, consult the doctor.

Take Zali exactly as follows:

Prevention of blood clots after hip or knee replacement surgery (arthroplasty)
The recommended dose is 220 mg once daily(taken as 2 capsules of 110 mg).
If kidney function is reducedby more than half or in patients aged 75 years or over, the recommended dose is 150 mg once daily(taken as 2 capsules of 75 mg).
In patients taking medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Zali is 150 mg once daily(taken as 2 capsules of 75 mg).
Patient taking verapamil-containing medicineswith reduced kidney functionshould receive a reduced dose of 75 mg of Zali due to an increased risk of bleeding.
In both types of surgery, treatment should not be started if there is bleeding from the surgical site. If it is not possible to start treatment the day after surgery, it should be started with a dose of 2 capsules once daily.
After knee replacement surgery
Zali treatment should be started with a single capsule within 1 to 4 hours after the end of surgery. Then, 2 capsules should be taken once daily for a total of 10 days.
After hip replacement surgery
Zali treatment should be started with a single capsule within 1 to 4 hours after the end of surgery. Then, 2 capsules should be taken once daily for a total of 28 to 35 days.
Prevention of blood clots in the brain and body due to irregular heart rhythm and treatment of blood clots in the legs and lungs and prevention of repeated blood clots in the legs and lungs
The recommended dose is 300 mg taken as one 150 mg capsule twice daily.
In patients aged 80 years or over, the recommended dose is 220 mg taken as one 110 mg capsule twice daily.
Patient taking verapamil-containing medicinesshould receive a reduced dose of 220 mg of Zali taken as one 110 mg capsule twice daily due to a possible increased risk of bleeding.
In patients with a potentially increased risk of bleeding, the doctor may recommend a dose of 220 mg taken as one 110 mg capsule twice daily.
Treatment with this medicine can be continued if the patient needs to restore normal heart function using a procedure called cardioversion. Zali should be taken as instructed by the doctor.
In the case of implantation of a medical device (stent) into a blood vessel to maintain its patency using a procedure called percutaneous coronary intervention with stent implantation, the patient may receive Zali treatment after the doctor has confirmed that blood clotting is under control. Zali should be taken as instructed by the doctor.
Treatment of blood clots and prevention of repeated blood clots in children
Zali should be taken twice daily, one dose in the morning and one dose in the evening, at approximately the same time every day. The interval between doses should be approximately 12 hours.
The recommended dose depends on the age and weight of the child. The doctor will determine the correct dose. The doctor may adjust the dose during treatment. All other medicines should be continued unless the doctor instructs to stop taking them.
A single dose of Zali to be taken twice daily, in milligrams (mg), depending on the child's weight in kilograms (kg) and age in years:

Age in years

8 to <9 9 to 10 11 12 13 14 15 16 17 <10< h4>

to
to
to
to
to
to
to
to
<11
<12
<13
<14
<15
<16
<17
<18
>81

300 mg

71 to <81

as two 150 mg capsules

61 to <71 or

four 75 mg capsules

260 mg

51 to <61

as one 110 mg capsule plus one 150 mg capsule
or
one 110 mg capsule plus two 75 mg capsules

41 to <51

220 mg

Body weight [kg]

as two 110 mg capsules

31 to <41

185 mg

as one 75 mg capsule plus one 110 mg capsule

150 mg

26 to <31

as one 150 mg capsule
or

21 to <26

two 75 mg capsules

16 to <21

One 110 mgcapsule

13 to <16

One

11 to <13

capsule

75 mg

Indicates that no dosing instructions can be given.

How to take Zali

Zali can be taken with or without food. The capsules should be swallowed whole with a glass of water to facilitate passage into the stomach. They should not be broken, chewed, or the pellets emptied from the capsule, as this may increase the risk of bleeding.

Changing anticoagulant medicine

Do not change anticoagulant medicine without receiving detailed instructions from your doctor.

Taking a higher dose of Zali than recommended

Taking too much of this medicine increases the risk of bleeding. If the patient has taken too many capsules, they should contact their doctor immediately. Specific treatments are available.

Missing a dose of Zali

Prevention of blood clots after hip or knee replacement surgery (arthroplasty)
Continue taking the missed daily dose of Zali at the same time the next day. Do not take a double dose to make up for the missed dose.
Adult use: Prevention of blood clots in the brain and body due to irregular heart rhythm and treatment of blood clots in the legs and lungs and prevention of repeated blood clots in the legs and lungs
A missed dose can be taken up to 6 hours before the next scheduled dose.
If there are less than 6 hours until the next scheduled dose, do not take the missed dose.
Do not take a double dose to make up for the missed dose.

Stopping Zali treatment

Zali should be taken as instructed by the doctor. Do not stop taking this medicine without consulting your doctor first, as the risk of blood clots may be higher if treatment is stopped prematurely. Contact your doctor if you experience indigestion after taking Zali.
If you have any further doubts 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. Zali affects the blood clotting system, so most side effects are related to symptoms such as bruising or bleeding. Severe or heavy bleeding may occur, which is the most serious side effect and can lead to disability, be life-threatening, or even fatal, regardless of location. In some cases, these bleedings may not be visible.
In case of bleeding that does not stop by itself or symptoms of excessive bleeding (unusual weakness, fatigue, pallor, dizziness, headache, or unexplained swelling), contact your doctor immediately. The doctor may decide to monitor the patient closely or change the medicine.
In case of a severe allergic reaction that can cause breathing difficulties or dizziness, contact your doctor immediately.
Side effects are listed below by frequency:

• Frequent (may affect up to 1 in 10 people):
• Decreased hemoglobin levels in the blood (a substance in red blood cells)
• Abnormal liver function test results
• Uncommon (may affect up to 1 in 100 people):
• Bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including urine discoloration due to blood), or bleeding under the skin
• Blood clots or bruising after surgery
• Blood in the stool, as detected by laboratory tests
• Decreased red blood cell count
• Decreased hematocrit
• Allergic reaction
• Vomiting
• Diarrhea
• Nausea
• Wound secretion (oozing of fluid from the wound)
• Increased liver enzyme activity
• Jaundice (yellowing of the skin or whites of the eyes due to liver or blood disease)

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

• Bleeding
• Bleeding may occur into the brain, from the surgical wound, from the injection site, or from the catheter insertion site
• Wound secretion with blood
• Coughing up blood or blood-tinged sputum
• Decreased platelet count
• Decreased red blood cell count after surgery
• Severe allergic reaction causing breathing difficulties or dizziness
• Severe allergic reaction causing facial or throat swelling
• Skin rash with red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin color or appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Esophagitis or gastritis
• Gastroesophageal reflux disease
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Wound secretion
• Unknown frequency (frequency cannot be estimated from the available data):
• Difficulty breathing or wheezing
• Decreased white blood cell count (which helps fight infections)
• Hair loss

Prevention of blood clots in the brain and body due to irregular heart rhythm
Frequent (may affect up to 1 in 10 people):

• Bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including urine discoloration due to blood), or bleeding under the skin
• Decreased red blood cell count
• Abdominal pain or stomach pain
• Indigestion
• Diarrhea
• Nausea
• Uncommon (may affect up to 1 in 100 people):
• Bleeding
• Bleeding may occur from hematomas, from the rectum, or into the brain
• Blood clots
• Coughing up blood or blood-tinged sputum
• Decreased platelet count
• Decreased hemoglobin levels in the blood (a substance in red blood cells)
• Allergic reaction
• Sudden change in skin color or appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Esophagitis or gastritis
• Gastroesophageal reflux disease
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results

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

• Bleeding may occur into the joint, from the surgical wound, from the injection site, or from the catheter insertion site
• Severe allergic reaction causing breathing difficulties or dizziness
• Severe allergic reaction causing facial or throat swelling
• Skin rash with red, raised, itchy bumps due to an allergic reaction
• Decreased hematocrit
• Increased liver enzyme activity
• Jaundice (yellowing of the skin or whites of the eyes due to liver or blood disease)
• Unknown frequency (frequency cannot be estimated from the available data):
• Difficulty breathing or wheezing
• Decreased white blood cell count (which helps fight infections)
• Hair loss

Treatment of blood clots in the legs and lungs and prevention of repeated blood clots in the legs and lungs
Frequent (may affect up to 1 in 10 people):

• Bleeding may occur from the nose, into the stomach or intestines, from the rectum, from the penis/vagina or urinary tract (including urine discoloration due to blood), or bleeding under the skin
• Indigestion
• Uncommon (may affect up to 1 in 100 people):
• Bleeding
• Bleeding may occur into the joint or due to injury
• Bleeding may occur from hematomas
• Decreased red blood cell count
• Blood clots
• Coughing up blood or blood-tinged sputum
• Allergic reaction
• Sudden change in skin color or appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Esophagitis or gastritis
• Gastroesophageal reflux disease
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Diarrhea
• Abnormal liver function test results
• Increased liver enzyme activity

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

• Bleeding may occur from the surgical wound, from the injection site, or from the catheter insertion site, or bleeding into the brain
• Decreased platelet count
• Severe allergic reaction causing breathing difficulties or dizziness
• Severe allergic reaction causing facial or throat swelling
• Skin rash with red, raised, itchy bumps due to an allergic reaction
• Difficulty swallowing
• Unknown frequency (frequency cannot be estimated from the available data):
• Difficulty breathing or wheezing
• Decreased hemoglobin levels in the blood (a substance in red blood cells)
• Decreased hematocrit
• Decreased white blood cell count (which helps fight infections)
• Jaundice (yellowing of the skin or whites of the eyes due to liver or blood disease)
• Hair loss

Treatment of blood clots and prevention of repeated blood clots in children
Frequent (may affect up to 1 in 10 people):

• Decreased red blood cell count
• Decreased platelet count
• Skin rash with red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin color or appearance
• Blood clots
• Nosebleeds
• Gastroesophageal reflux disease
• Vomiting
• Nausea
• Diarrhea
• Indigestion
• Hair loss
• Increased liver enzyme activity
• Uncommon (may affect up to 1 in 100 people):
• Decreased white blood cell count (which helps fight infections)
• Bleeding may occur into the stomach or intestines, into the brain, from the rectum, from the penis/vagina or urinary tract (including urine discoloration due to blood), or bleeding under the skin
• Decreased hemoglobin levels in the blood (a substance in red blood cells)
• Decreased hematocrit
• Itching
• Coughing up blood or blood-tinged sputum
• Abdominal pain or stomach pain
• Esophagitis or gastritis
• Allergic reaction
• Difficulty swallowing
• Jaundice (yellowing of the skin or whites of the eyes due to liver or blood disease)

Unknown frequency (frequency cannot be estimated from the available data):

• Absence of white blood cells (which help fight infections)
• Severe allergic reaction causing breathing difficulties or dizziness
• Severe allergic reaction causing facial or throat swelling
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur into the joint, from the wound, from the surgical wound, from the injection site, or from the catheter insertion site
• Bleeding may occur from hematomas
• Stomach or intestinal ulcer (including esophageal ulceration)
• Abnormal liver function test results

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych (Office for Registration of Medicinal Products, Medical Devices, and Biocides): 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.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zali

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or blister after "EXP". The expiry date refers to the last day of the month.
There are no special storage instructions for this medicinal product.
Store in the original packaging to protect from moisture.
Do not put the capsules in pill boxes or organizers unless they are in their original packaging.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Zali contains

• The active substance is dabigatran. Each hard capsule contains 110 mg of dabigatran etexilate (as mesylate).
• The other ingredients are: microcrystalline cellulose, sodium croscarmellose, crospovidone (type A), tartaric acid (in the form of pellets), hydroxypropylcellulose (470cp), mannitol, talc, and magnesium stearate.
• The capsule shell contains red iron oxide (E172), titanium dioxide (E171), and hypromellose.
• The black ink used for printing contains shellac, black iron oxide (E172), and potassium hydroxide.

What Zali looks like and contents of the pack

Zali 110 mg is a hard capsule with a non-transparent pink cap and body with the imprint "DA110".
This medicine is available in packs of 10, 30, or 60 hard capsules, a multipack containing 3 packs of 60 hard capsules (180 hard capsules), and a multipack containing 2 packs of 50 hard capsules (100 hard capsules) in perforated blisters of aluminum/OPA/aluminum/PE, divided into single doses with a desiccant.
Not all pack sizes may be marketed.

Marketing authorization holder

Farmak International Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw
tel. +48 22 822 93 06

Manufacturer

TOWA Pharmaceutical Europe, S.L.
C/ de Sant Martí, 75-97
08107, Martorelles, Barcelona, Spain
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola PLA 3000, Malta

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

Poland
Zali

Date of last revision of the leaflet: