Zali

Package Leaflet: Information for the Patient

Zali, 150 mg, Hard Capsules

Dabigatran Etexilate

Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medication has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your 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 pack 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 the formation of blood clots in the brain (stroke) and other blood vessels in the patient's body, if the patient has a form of irregular heart rhythm called atrial fibrillation not caused by a heart valve problem and at least one additional risk factor.
• treat blood clots in the legs and lungs and prevent the recurrence of blood clots in the legs and lungs.

Zali is used in children to:

• treat blood clots and prevent the recurrence of blood clots.

2. Important information before taking Zali

When not to take Zali

• if you are allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6).
• if you have severe kidney impairment.
• if you are currently bleeding.
• if you have 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 you have an increased tendency to bleed. This can be congenital, of unknown cause, or caused by the use of other medications.

• if you are taking anticoagulant medications (e.g., warfarin, rivaroxaban, apixaban, or heparin), except when changing anticoagulant treatment, introducing a venous or arterial catheter, 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 you have severe liver impairment or liver disease that can lead to death.
• if you are taking oral ketoconazole or itraconazole, medications used to treat fungal infections.
• if you are taking oral cyclosporine, a medication used to prevent organ rejection.
• if you are taking dronedarone, a medication used to treat heart rhythm disorders.
• if you are taking a combination medication containing glecaprevir and pibrentasvir, an antiviral medication used to treat hepatitis C.
• if you have a prosthetic heart valve that requires continuous anticoagulation.

Warnings and precautions

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

• if you have an increased risk of bleeding, such as:
• if you have recently experienced bleeding.
• if you have had a surgical biopsy within the last month.
• if you have had a serious injury (e.g., bone fracture, head injury, or any injury requiring surgical treatment).
• if you have esophageal or stomach inflammation.
• if you have stomach acid reflux into the esophagus.
• if you are taking medications that may increase the risk of bleeding. See "Zali and other medications" below.
• if you are taking anti-inflammatory medications, such as acetylsalicylic acid, ibuprofen, or diclofenac.
• if you have a heart infection (bacterial endocarditis).
• if you have reduced kidney function or are dehydrated (feeling thirsty and producing a reduced amount of dark, concentrated, or foamy urine).
• if you are over 75 years old.
• if you are an adult and weigh 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 previous heart attack or if you have been diagnosed with conditions that increase the risk of a heart attack.
• if you have liver disease that affects blood test results. In this case, the use of this medication is not recommended.

When to exercise special caution when taking Zali

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

Zali and other medications

Tell your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take.
In particular, you should tell your doctor before taking Zali if you are taking any of the following medications:

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

Pregnancy and breastfeeding

The effect of Zali on pregnancy and the unborn child is not known. You should not take this medication during pregnancy unless your doctor considers it safe.
Women of childbearing age should avoid becoming pregnant while taking Zali.
You should 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 medication 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 capsules whole. There are other age-appropriate formulations for the treatment of children under 8 years of age.
This medication should always be taken exactly as your doctor has instructed. If you are unsure, consult your doctor.

Take Zali exactly as follows:

Prevention of blood clots in the brain and body by preventing the formation of clots that occur during irregular heart rhythm and treatment of blood clots in the legs and lungs and prevention of recurrence of blood clots in the legs and lungs
The recommended dose is 300 mg taken as one 150 mg capsule twice a day.
For patients aged 80 years or older, the recommended dose is 220 mg taken as one 110 mg capsule twice a day.
Patients taking medications containing verapamilshould receive reduced-dose Zali treatment of 220 mg taken as one 110 mg capsule twice a daydue to the potential increased risk of bleeding.
For patients with potentially increased risk of bleeding, the doctor may recommend a dose of 220 mg taken as one 110 mg capsule twice a day.
Zali can be continued if the patient needs to restore normal heart function using a procedure called cardioversion or catheter ablation in atrial fibrillation. Zali should be taken exactly as your doctor has instructed.
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 control has been achieved. Zali should be taken exactly as your doctor has instructed.
Treatment of blood clots and prevention of recurrence of blood clots in children
Zali should be taken twice a day, one dose in the morning and one dose in the evening, approximately at the same time every day. The interval between doses should be approximately 12 hours.
The recommended dose depends on age and body weight. The doctor will determine the correct dose. The doctor may adjust the dose during treatment. All other medications should be continued unless the doctor instructs otherwise.
A single dose of Zali, which should be administered twice a day, in milligrams (mg) based on the patient's body 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 provided.

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 spilled from the capsule, as this may increase the risk of bleeding.

Changing anticoagulant medication

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

Taking a higher dose of Zali than recommended

Taking too much of this medication increases the risk of bleeding. If you have taken too many capsules, contact your doctor immediately. Specific treatments are available.

Missing a dose of Zali

A missed dose can be taken up to 6 hours before the next scheduled dose.
If it is 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 a missed dose.

Stopping Zali treatment

Zali should be taken exactly as your doctor has instructed. Do not stop taking this medication without consulting your doctor first, as the risk of blood clot formation may be higher if treatment is stopped prematurely. You should consult your doctor if you experience indigestion after taking Zali.
If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Zali 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 can occur, which is the most serious side effect and can lead to disability, be life-threatening, or even fatal, regardless of the location. In some cases, these bleeds may not be visible.
If you experience bleeding that does not stop on its own or symptoms of excessive bleeding (exceptional weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), you should contact your doctor immediately. Your doctor may decide to monitor you closely or change your medication.
If you experience a severe allergic reaction that can cause difficulty breathing or dizziness, you should contact your doctor immediately.
The following side effects are grouped by frequency:

• 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 discolored pink or red due to the presence of blood), or bleeding under the skin
• Decreased red blood cell count
• Abdominal pain or stomach pain
• Indigestion
• Frequent loose or liquid stools
• Nausea
• Uncommon (may affect up to 1 in 100 people):
• Bleeding
• Bleeding may occur from hematomas, from the rectum, or from the brain
• Formation of hematomas
• Coughing up blood or sputum discolored with blood
• Decreased platelet count
• Decreased hemoglobin content in the blood (a substance in red blood cells)
• Allergic reaction
• Sudden change in skin color or appearance
• Itching
• Stomach or intestinal ulcers (including esophageal ulcers)
• Esophageal and stomach inflammation
• Acid reflux from the stomach into the esophagus
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results
• Rare (may affect up to 1 in 1,000 people):
• Bleeding may occur into a joint, from a surgical wound, from an injection site, or from a catheter insertion site
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing facial or throat swelling
• Skin rash in the form of dark red, raised, itchy bumps caused by an allergic reaction
• Decreased red blood cell count
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver or blood disease
• Hair loss
• Unknown frequency (frequency cannot be estimated from the available data):
• Difficulty breathing or wheezing
• Decreased white blood cell count (which helps fight infections)

Treatment of blood clots in the legs and lungs and prevention of recurrence of 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 discolored pink or red due to the presence of blood), or bleeding under the skin
• Indigestion
• Uncommon (may affect up to 1 in 100 people):
• Bleeding
• Bleeding may occur into a joint or due to injury
• Bleeding may occur from hematomas
• Decreased red blood cell count
• Formation of hematomas
• Coughing up blood or sputum discolored with blood
• Allergic reaction
• Sudden change in skin color or appearance
• Itching
• Stomach or intestinal ulcers (including esophageal ulcers)
• Esophageal and stomach inflammation
• Acid reflux from the stomach into the esophagus
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent loose or liquid stools
• Abnormal liver function test results
• Increased liver enzyme activity
• Rare (may affect up to 1 in 1,000 people):
• Bleeding may occur from a surgical wound, from an injection site, or from a catheter insertion site or bleeding into the brain
• Decreased platelet count
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing facial or throat swelling
• Skin rash in the form of dark red, raised, itchy bumps caused by an allergic reaction
• Difficulty swallowing
• Unknown frequency (frequency cannot be estimated from the available data):
• Difficulty breathing or wheezing
• Decreased hemoglobin content in the blood (a substance in red blood cells)
• Decreased red blood cell count
• Decreased white blood cell count (which helps fight infections)
• Yellowing of the skin or whites of the eyes due to liver or blood disease
• Hair loss

In clinical trials, the number of heart attacks in patients taking Zali was higher than in those taking warfarin. The overall number of events was small.

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

• Decreased red blood cell count
• Decreased platelet count
• Skin rash in the form of dark red, raised, itchy bumps caused by an allergic reaction
• Sudden change in skin color or appearance
• Formation of hematomas
• Nosebleeds
• Acid reflux from the stomach into the esophagus
• Vomiting
• Nausea
• Frequent loose or liquid stools
• 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 discolored pink or red due to the presence of blood), or bleeding under the skin
• Decreased hemoglobin content in the blood (a substance in red blood cells)
• Decreased red blood cell count
• Itching
• Coughing up blood or sputum discolored with blood
• Abdominal pain or stomach pain
• Esophageal and stomach inflammation
• Allergic reaction
• Difficulty swallowing
• 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):
• Lack of white blood cells (which help fight infections)
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing facial or throat swelling
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur into a joint, from a wound, from a surgical wound, from an injection site, or from a catheter insertion site
• Bleeding may occur from hematomas
• Stomach or intestinal ulcers (including esophageal ulcers)
• Abnormal liver function test results

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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.
By reporting side effects, you can help provide more information on the safety of this medication.

5. How to store Zali

Keep this medication out of the sight and reach of children.
Do not use this medication after the expiry date stated on the carton or blister after:
Expiry date. The expiry date refers to the last day of the month stated.
No special precautions for storage are necessary.
Store in the original package to protect from moisture.
Do not put the capsules in pill boxes or pill organizers unless they are stored in their original packaging.
Medications should not be disposed of via wastewater. Ask your pharmacist how to dispose of medications no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Zali contains

• The active substance is dabigatran. Each hard capsule contains 150 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 150 mg is a hard capsule with a non-transparent pink cap and body with the imprint "DA150".
This medication is available in packs containing 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: