Daxanlo

Patient Information Leaflet

Daxanlo, 150 mg, hard capsules
Dabigatranum etexilatum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

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

Contents of the leaflet

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

1. What Daxanlo is and what it is used for

Daxanlo contains dabigatran etexilate as the active substance and belongs to a group of medicines called anticoagulants. It works by blocking a substance in the body that is responsible for blood clot formation.
Daxanlo is used in adults:

• to prevent the formation of blood clots in the brain (stroke) and in other blood vessels in the body when the patient has an irregular heart rhythm known as non-valvular atrial fibrillation and at least one additional risk factor.
• to treat blood clots in the veins of the legs and lungs, and to prevent recurrence of blood clots in the veins of the legs and lungs.

Daxanlo is used in children:

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

2. Important information before taking Daxanlo

When not to take Daxanlo

• 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 experiencing bleeding.
• if the patient has an internal organ disease that increases the risk of major bleeding (e.g. gastric ulcer, brain injury or intracranial hemorrhage, recent brain or eye surgery).
• if the patient has an increased tendency to bleed, which may be congenital, of unknown cause, or caused by taking other medicines.
• if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, apixaban, or heparin), except when switching anticoagulant therapy, during insertion of a venous or arterial catheter where heparin is administered through the catheter to maintain its patency, or during catheter ablation procedures for atrial fibrillation to restore normal heart rhythm.
• 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 rejection of transplanted organs.
• 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 virus infection.
• if the patient has a mechanical heart valve requiring continuous anticoagulant therapy.

Warnings and precautions
Before starting Daxanlo, discuss this with your doctor or pharmacist. If symptoms occur during treatment with this medicine or if the patient has undergone surgery, consult a doctor.
The patient should inform the doctor if they currently have or have previously had any medical conditions or diseases, especially the following:

• if the patient has an increased risk of bleeding, such as:
• if the patient has recently experienced bleeding.
• if the patient has undergone a surgical tissue 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 inflammation of the esophagus or stomach.
• if the patient has gastroesophageal reflux (backflow of stomach acid into the esophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below “Daxanlo with other medicines”.
• if the patient is taking nonsteroidal anti-inflammatory drugs such as diclofenac, ibuprofen, piroxicam.
• if the patient has an infection in the heart (bacterial endocarditis).
• if the patient has reduced kidney function or is dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated) and/or foamy urine).
• if the patient is over 75 years of age.
• if the patient is an adult weighing 50 kg or less.
• only when used in children: if the child has an infection around or within the brain.
• if the patient has had a heart attack or has conditions diagnosed to increase the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such cases, Daxanlo is not recommended.

When to exercise special caution when taking Daxanlo

• if the patient needs to undergo surgery: in such cases, temporary discontinuation of Daxanlo is necessary due to increased risk of bleeding during and immediately after surgery. It is very important to take Daxanlo exactly as directed by the doctor before and after surgery.

• if surgery requires insertion of a catheter or injection into the spinal canal (e.g. for epidural or spinal anesthesia or for pain relief):

• it is very important to take Daxanlo exactly as prescribed by the doctor.

• the patient should immediately inform the doctor if numbness or weakness in the lower limbs or problems with the bowel or bladder occur after the anesthesia wears off, as urgent medical care may be needed.

• if the patient falls or sustains an injury during treatment, especially to the head. Immediate medical evaluation is required. The doctor will assess whether there is an increased risk of bleeding.

• if the patient has a condition called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment adjustment is necessary.

Daxanlo with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. In particular, before taking Daxanlo, tell the doctor if the patient is taking any of the following
medicines:

• Medicines that reduce blood clotting (e.g. warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid).
• Medicines used to treat fungal infections (e.g. ketoconazole, itraconazole), unless these are applied only topically to the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking verapamil-containing medicines, the doctor may recommend a lower dose of Daxanlo depending on the condition for which it was prescribed. See section 3.
• Medicines used to prevent rejection of transplanted organs (e.g. tacrolimus, cyclosporine).
• A combination medicine containing glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C virus infection).
• Anti-inflammatory and pain-relieving medicines (e.g. acetylsalicylic acid, ibuprofen, diclofenac).
• St. John’s wort, a herbal medicine used to treat depression.
• Antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin-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
It is not known what effect Daxanlo has on pregnancy and the unborn child. Daxanlo should not be taken during pregnancy unless the doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Daxanlo.
Breastfeeding is not recommended during treatment with Daxanlo.

Driving and operating machinery
Daxanlo has no effect or has a negligible effect on the ability to drive and operate machinery.

3. How to take Daxanlo

Daxanlo can be used in adults and children aged 8 years or older who are able to swallow capsules whole.
Other age-appropriate formulations are available for treating children under 8 years of age.
This medicine should always be taken as prescribed by the doctor. If in doubt, consult your doctor.
Daxanlo should be taken as follows:
Prevention of blood clots in blood vessels of the brain and body by preventing the formation of clots due to irregular heart rhythm, and treatment of blood clots in the veins of the legs and lungs, as well as prevention of recurrence of blood clots in the veins of the legs and lungs.
The recommended dose is 300 mg taken as one 150 mg capsule twice daily.
In patients aged 80 years or older, the recommended dose of Daxanlo is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medicines containing verapamil should receive a reduced dose of Daxanlo of 220 mg taken as one 110 mg capsule twice daily due to the possible increased risk of bleeding.
In patients with potentially increased risk of bleeding, the doctor may recommend treatment with Daxanlo at a dose of 220 mg taken as one 110 mg capsule twice daily.
Treatment with Daxanlo may be continued if the patient requires restoration of normal heart rhythm through a procedure called cardioversion or through a procedure called catheter ablation for atrial fibrillation. Daxanlo should be taken as directed by the doctor.
In the case of implantation of a medical device (stent) into a blood vessel to keep it open, using a procedure called percutaneous coronary intervention with stent implantation, the patient may receive treatment with Daxanlo after the doctor has confirmed adequate control of blood clotting. Daxanlo should be taken as directed by the doctor.
Treatment of blood clots and prevention of recurrence of blood clots in children
Daxanlo should be taken twice daily, one dose in the morning and one dose in the evening, approximately at the same time each day. The interval between doses should be as close as possible to 12 hours.
The recommended dose depends on body weight and age. The doctor will determine the correct dose. The doctor may adjust the dose during treatment. Continue taking all other medications unless the doctor advises otherwise.
Table 1 shows the single and total daily doses of Daxanlo in milligrams (mg).
The doses depend on the patient's body weight in kilograms (kg) and age in years.
Table 1: Dosing table for Daxanlo capsules

Single doses requiring combination of more than one capsule:
300 mg: two 150 mg capsules or
four 75 mg capsules
260 mg: one 110 mg capsule and one 150 mg capsule or
one 110 mg capsule and two 75 mg capsules
220 mg: as two 110 mg capsules
185 mg: as one 75 mg capsule and one 110 mg capsule
150 mg: as one 150 mg capsule or
two 75 mg capsules

How to take Daxanlo
Daxanlo can be taken with or without food. The capsules should be swallowed whole,
with a glass of water, to facilitate passage into the stomach. Do not crush,
chew, or empty the pellets from the capsule, as this may increase the risk of bleeding.

Instructions for opening blisters
The following pictogram illustrates how to remove Daxanlo capsules from the blister pack.
To remove a capsule from the blister:

1. Hold the blister at the edges and separate one blister cell from the rest of the blister by gently bending and tearing along the perforation around it.
2. Lift the edge of the foil and completely peel it off.
3. Push the capsule out onto your hand.
4. Swallow the capsule whole with a glass of water.
   • Do not push the capsule through the blister foil.
   • Do not peel off the foil until the capsule is needed.

Instructions for opening the container

• To open the container, press down and turn the cap.
• After removing a capsule and taking the dose, immediately close the container tightly with the cap.

Switching anticoagulant medication
Do not switch anticoagulant medication without receiving specific instructions from your doctor.

Accidental overdose of Daxanlo
Taking too high a dose of Daxanlo increases the risk of bleeding. If a patient has taken too many Daxanlo capsules, contact a doctor immediately. Specific treatment methods are available.

Missed dose of Daxanlo
A missed dose may be taken if there is at least 6 hours before the next scheduled dose.
If less than 6 hours remain 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 Daxanlo treatment
Daxanlo should be taken as prescribed by the doctor. Do not stop taking Daxanlo without consulting your doctor first, as the risk of developing a blood clot may be higher if treatment is stopped prematurely. Contact your doctor if gastrointestinal discomfort occurs after taking Daxanlo.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Daxanlo affects the blood clotting system, so most adverse reactions involve symptoms such as bruising or bleeding.
Severe or major bleeding may occur, which is the most serious adverse reaction, and regardless of location, it may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.
If bleeding occurs that does not stop spontaneously, or symptoms of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling) appear, contact your doctor immediately. The doctor may decide to place the patient under close observation or change the treatment.
In case of a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

The possible adverse reactions listed below are grouped according to their frequency of occurrence:

Prevention of thromboembolic events in blood vessels of the brain and body by preventing the formation of clots that occur due to irregular heart function

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

• Bleeding may occur from the nose, into the stomach or intestines, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in the number of red blood cells in the blood
• Abdominal pain or stomach pain
• Indigestion
• Frequent passage of loose or watery stools
• Nausea

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

• Bleeding
• Bleeding may occur from haemorrhoids, from the rectum, or into the brain
• Formation of bruises (haematomas)
• Coughing up blood or blood-stained sputum
• Decrease in the number of platelets in the blood
• Decrease in haemoglobin levels in the blood (a substance in red blood cells)
• Allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results in laboratory tests

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

• Bleeding into a joint, from a surgical incision site, from a wound, from an injection site, or from the site of intravenous catheter insertion
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash characterized by dark red, raised, itchy bumps due to an allergic reaction
• Decrease in blood cell count
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorders

Frequency not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decrease in the number of, or even absence of, white blood cells (which help fight infections)
• Hair loss

In clinical trials, the number of heart attacks was numerically higher with dabigatran etexilate than with warfarin. The overall number of events was low.

Treatment of blood clots in the legs and lungs, and prevention of recurrence of blood clots in the legs and (or) lungs

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

• Bleeding may occur from the nose, into the stomach or intestines, from the anus, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Indigestion

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

• Bleeding
• Bleeding may occur into a joint or following injury
• Bleeding from haemorrhoids may occur
• Decrease in the number of red blood cells in the blood
• Formation of bruises (haematomas)
• Coughing up blood or blood-stained sputum
• Allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Nausea
• Vomiting
• Abdominal pain or stomach pain
• Frequent passage of loose or watery stools
• Abnormal liver function test results in laboratory tests
• Increased liver enzyme activity

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

• Bleeding from a surgical incision site, or from an injection site or site of intravenous catheter insertion, or bleeding from the brain
• Decrease in the number of platelets in the blood
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash characterized by dark red, raised, itchy bumps due to an allergic reaction
• Difficulty swallowing

Frequency not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decrease in haemoglobin levels in the blood (a substance in red blood cells)
• Decrease in blood cell count
• Decrease in the number of, or even absence of, white blood cells (which help fight infections)
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorders
• Hair loss

In clinical trials, the number of heart attacks was numerically higher with dabigatran etexilate than with warfarin. The overall number of events was low. No difference in the number of heart attacks was observed between patients treated with dabigatran and those receiving placebo.

Treatment of blood clots and prevention of recurrence of blood clots in children

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

• Decrease in the number of red blood cells in the blood
• Decrease in the number of platelets in the blood
• Skin rash characterized by dark red, raised, itchy bumps due to an allergic reaction
• Sudden change in skin colour and appearance
• Formation of bruises (haematomas)
• Nosebleeds
• Regurgitation of stomach contents into the oesophagus (reflux)
• Vomiting
• Nausea
• Frequent passage of loose or watery stools
• Indigestion
• Hair loss
• Increased liver enzyme activity

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

• Decrease in the number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, from the brain, from the anus, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in haemoglobin levels in the blood (a substance in red blood cells)
• Decrease in blood cell count
• Itching
• Coughing up blood or blood-stained sputum
• Abdominal pain or stomach pain
• Inflammation of the oesophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorders

Frequency not known (frequency cannot be estimated from available data):

• Absence of white blood cells (which help fight infections)
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur into a joint, from a wound, from a surgical incision site, from an injection site, or from the site of intravenous catheter insertion
• Bleeding from haemorrhoids may occur
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results in laboratory tests

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Daxanlo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister, or container label after: EXP. The expiry date refers to the last day of the stated month.
Blister:
There are no special storage temperature requirements for this medicine.
Store in the original packaging to protect from light and moisture.
Container:
There are no special storage temperature requirements for this medicine.
Store in the original packaging to protect from light and moisture.
Keep the container tightly closed.
Medicines must not be disposed of via the sewage system or in 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 Daxanlo contains

• The active substance is dabigatran etexilate. Each hard capsule contains 150 mg of dabigatran etexilate (as mesilate).
• The other components (excipients) are: capsule contents: tartaric acid (pellets), hypromellose (6 mPa*s), hydroxypropylcellulose (470 mPa*s), and talc; capsule shell: titanium dioxide (E 171), indigo carmine (E 132), carrageenan, potassium chloride, hypromellose (type 2910); printing ink: shellac, black iron oxide (E 172), potassium hydroxide.

What Daxanlo looks like and contents of the pack
Daxanlo 150 mg hard capsules: the capsule cap is blue, the body is white or almost white, with a black "150" printed longitudinally; length approximately 24 mm.
The capsule contents are off-white to light yellowish pellets.
Daxanlo 150 mg hard capsules are available in cardboard cartons containing:

• 10 x 1, 30 x 1, 60 x 1, 100 x 1, or bulk packs of 100 (2 packs of 50 x 1) or 180 (3 packs of 60 x 1) hard capsules in perforated, single-dose, peelable blisters.
• 60 hard capsules in a bottle with child-resistant closure or 3 bottles each containing 60 hard capsules with child-resistant closure.

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 on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw, Poland
telephone: +48 22 573 75 00