Zali

Package Leaflet: Information for the Patient

Zali, 75 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, as you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medication has been prescribed to a specific person. Do not pass it on to others. The medication may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform 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 Package 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 medications 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.

Zali is used in children to:

• treat blood clots and prevent recurrence of 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 medication (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 significant bleeding (e.g., stomach ulcer, brain injury or bleeding, 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 medications.
• if the patient is taking anticoagulant medications (e.g., warfarin, rivaroxaban, apixaban, or heparin), except when changing anticoagulant treatment, introducing a catheter into a vein or artery, or when heparin is administered to maintain catheter patency or restore normal heart function through 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, medications used to treat fungal infections.
• if the patient is taking oral cyclosporine, a medication used to prevent transplant rejection.
• if the patient is taking dronedarone, a medication used to treat heart rhythm disorders.
• if the patient is taking a combination medication containing glecaprevir and pibrentasvir, an antiviral medication used to treat hepatitis C.
• if the patient has a mechanical heart valve that requires continuous anticoagulation.

Warnings and Precautions

Before starting Zali, discuss it with your doctor. If you experienced symptoms or underwent surgery while taking this medication, consult your doctor.
The patient should inform their 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 had a serious injury (e.g., bone fracture, head injury, or any injury requiring surgical treatment).
• if the patient has esophageal or stomach inflammation.
• if the patient has stomach acid reflux.
• if the patient is taking medications that may increase the risk of bleeding. See "Zali and Other Medications" below.
• if the patient is taking anti-inflammatory medications, such as diclofenac, ibuprofen, or piroxicam.
• if the patient has a heart infection (bacterial endocarditis).
• if the patient has reduced kidney function or is dehydrated (feeling thirsty and producing a small amount of dark, concentrated 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 pediatric use: if the child has an infection around or in the brain.
• in case of a history of heart attack or if the patient has been diagnosed with conditions that increase the risk of heart attack.
• if the patient has liver disease that affects blood test results. In such cases, the use of this medication is not recommended.

When to Exercise Particular Caution When Taking Zali

• if the patient needs to undergo surgery: In such cases, 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 their 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 may be necessary.
• if the patient has fallen or injured themselves during treatment, especially if they have hit their head. The patient should seek medical attention immediately. 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 their doctor, who will decide whether to change the 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:

• Medications that reduce blood clotting (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 transplant rejection (e.g., tacrolimus, cyclosporine).
• A combination medication containing glecaprevir and pibrentasvir (an antiviral medication used to treat hepatitis C).
• Anti-inflammatory and pain-relieving 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. This medication should not be taken during pregnancy unless the doctor considers it safe. Women of childbearing age should avoid becoming pregnant while taking Zali.
During Zali treatment, breastfeeding should be avoided.

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 pharmaceutical forms for treating children under 8 years of age.
This medication should always be taken exactly as the doctor has instructed. In case of doubts, consult a doctor.

Take Zali 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 each).
If kidney function is reducedby more than half or in patients aged 75 or over, the recommended dose is 150 mg once daily(taken as 2 capsules of 75 mg each).
In patients taking medications containing amiodarone, quinidine, or verapamil, the recommended dose of Zali is 150 mg once daily(taken as 2 capsules of 75 mg each).
Patient taking medications containing verapamil, with reduced kidney functionof more than half, should take a reduced dose of 75 mgof Zali due to increased bleeding risk.
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.
Treatment of blood clots and prevention of recurrent 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 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, to be taken twice daily, in milligrams (mg), based on the patient'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

This indicates that no dosing recommendations 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 emptied 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 More than the Recommended Dose of Zali

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

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.
Treatment of blood clots and prevention of recurrent blood clots in children.
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 your doctor. 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. Contact your doctor if you experience indigestion after taking Zali.
In case of any further doubts about the use of this medication, consult a doctor or pharmacist.

4. Possible Side Effects

Like all medications, 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 significant bleeding may 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 bleedings may not be visible.
In case of bleeding that does not stop on its own or symptoms of excessive bleeding (exceptional weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), contact your doctor immediately. The doctor may decide to monitor the patient closely or change the medication.
In case of a severe allergic reaction that may cause breathing difficulties or dizziness, contact your doctor immediately.
Possible side effects are listed below by frequency of occurrence:

• Frequent (may affect up to 1 in 10 people):
• Reduced 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, stomach, or intestines, brain, anus, penis/vagina, or urinary tract (including urine discoloration due to blood presence), or bleeding under the skin
• Formation of hematomas or bruising after surgery
• Blood in the stool, as indicated by laboratory tests
• Reduced red blood cell count
• Reduced hematocrit
• Allergic reaction
• Vomiting
• Frequent loose or liquid stools
• Nausea
• Wound secretion
• Increased liver enzyme activity
• Jaundice of the skin or 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 site, injection site, or catheter insertion site
• Blood-tinged secretion from the catheter insertion site
• Coughing up blood or bloody sputum
• Reduced platelet count
• Reduced red blood cell count after surgery
• Severe allergic reaction causing breathing difficulties or dizziness
• Severe allergic reaction causing facial or throat swelling
• Skin rash in the form of dark red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcers (including esophageal ulcers)
• Esophageal and stomach inflammation
• Acid reflux
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Wound secretion
• Wound secretion after surgery
• Frequency not known (frequency cannot be estimated from available data):
• Difficulty breathing or wheezing
• Reduced white blood cell count (which helps fight infections)
• Hair loss

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

• Reduced red blood cell count
• Reduced platelet count
• Skin rash in the form of dark red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin color and appearance
• Formation of hematomas
• Nosebleeds
• Acid reflux
• Vomiting
• Nausea
• Frequent loose or liquid stools
• Indigestion
• Hair loss
• Increased liver enzyme activity
• Uncommon (may affect up to 1 in 100 people):
• Reduced white blood cell count (which helps fight infections)
• Bleeding may occur into the stomach, intestines, brain, anus, penis/vagina, or urinary tract (including urine discoloration due to blood presence), or bleeding under the skin
• Reduced hemoglobin levels in the blood (a substance in red blood cells)
• Reduced hematocrit
• Itching
• Coughing up blood or bloody sputum
• Abdominal pain or stomach pain
• Esophageal and stomach inflammation
• Allergic reaction
• Difficulty swallowing
• Jaundice of the skin or eyes due to liver or blood disease
• Frequency not known (frequency cannot be estimated from 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, wound, surgical site, injection site, or 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 any not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Medicinal Product Monitoring 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 will help gather more information on the safety of this medication.

5. How to Store Zali

Store the medication out of sight and reach of children.
Do not use this medication after the expiry date stated on the carton or blister pack. 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 or household waste. Ask your pharmacist how to dispose of medications no longer needed. This will help protect the environment.

6. Contents of the Package and Other Information

What Zali Contains

• The active substance of Zali is dabigatran. Each hard capsule contains 75 mg of dabigatran etexilate (as mesylate).
• 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 Package

Zali 75 mg is a hard capsule with a non-transparent, pink cap and body, with "DA75" printed on it.
This medication is available in packages containing 10, 30, or 60 hard capsules in perforated blisters made 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: