Daroxomb

Package leaflet: Information for the user

Daroxomb, 110 mg, hard capsules
Dabigatranum etexilatum
Please read all of this leaflet carefully before taking this medicine, because 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. It may harm them, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Daroxomb is and what it is used for

Daroxomb 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 involved in blood clot formation.

Daroxomb is used in adults to:

• prevent the formation of blood clots in veins following hip or knee replacement surgery.
• prevent the formation of blood clots in the brain (stroke) and in other blood vessels in patients who have a type of irregular heartbeat called non-valvular atrial fibrillation and at least one additional risk factor.
• 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.

Daroxomb is used in children to:

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

2. Important information before taking Daroxomb

When not to take Daroxomb

• 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 function 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 trauma or intracranial hemorrhage, recent brain or eye surgery).
• if the patient has an increased tendency to bleed. This 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, inserting a venous or arterial catheter, when heparin is administered through the catheter to maintain its patency, or during a procedure called catheter ablation for atrial fibrillation to restore normal heart rhythm.
• if the patient has severe liver function impairment or liver disease that may lead to death.
• if the patient is taking oral ketoconazole or itraconazole, antifungal medicines used to treat fungal infections.
• if the patient is taking oral cyclosporine, a medicine used to prevent rejection of a transplanted organ.
• 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 had a mechanical heart valve implanted, which requires continuous use of blood-thinning medicines.

Warnings and precautions
Before starting treatment with Daroxomb, discuss this with your doctor. 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 have or have previously 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 a 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 inflammation of the esophagus or stomach.
• if the patient has gastroesophageal reflux (acid reflux into the esophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below "Daroxomb and other medicines".
• if the patient is taking nonsteroidal anti-inflammatory drugs 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 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 been diagnosed with conditions increasing the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such a case, use of this medicine is not recommended.

When to exercise special caution when taking Daroxomb

• if the patient needs to undergo surgery: In such a case, temporary discontinuation of Daroxomb is necessary due to the increased risk of bleeding during and immediately after surgery. It is very important to take Daroxomb exactly as directed by the doctor both before and after surgery.
• if surgery requires insertion of a catheter or administration of an injection into the spine (e.g. for epidural or spinal anesthesia or for pain relief):
• It is very important to take Daroxomb exactly as directed by the doctor both before and after surgery.
• The patient should immediately inform the doctor if they experience numbness or weakness in the legs or problems with the bowels or bladder after the anesthesia wears off, as urgent medical care is required.
• if the patient falls or sustains an injury during treatment, especially if the injury involves 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 autoimmune disorder causing increased risk of blood clots), the patient should inform their doctor, who will decide whether treatment adjustment is needed.

Daroxomb and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. In particular, before taking Daroxomb, 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). For patients taking medicines containing amiodarone, quinidine, or verapamil, the doctor may recommend a lower dose of Daroxomb depending on the condition for which the medicine was prescribed. See section 3.
• Medicines used to prevent organ rejection after transplantation (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 Daroxomb has on pregnancy or the unborn child. This medicine should not
be taken during pregnancy unless the doctor determines it is safe. Women of childbearing age should
use contraception to prevent pregnancy while taking Daroxomb.
Breastfeeding should not be performed while taking Daroxomb.

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

3. How to take Daroxomb

Daroxomb capsules 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 the doctor.
Daroxomb should be taken according to the following recommendations:
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).
In patients with renal function reduced by more than half or in patients aged 75 years or older, the recommended dose is 150 mg once daily (taken as 2 capsules of 75 mg).
In patients taking medications containing amiodarone, quinidine, or verapamil, the recommended dose of Daroxomb is 150 mg once daily (taken as 2 capsules of 75 mg).
Patients taking medications containing verapamil who also have renal function reduced by more than half should take a reduced dose of Daroxomb of 75 mg due to increased risk of bleeding.
In both types of procedures, treatment should not be initiated if there is bleeding at the surgical site. If treatment cannot be started by the next day after surgery, it should be initiated with a dose of 2 capsules once daily.
After knee replacement surgery
Treatment with Daroxomb should begin with one capsule taken 1 to 4 hours after completion of the surgical procedure. Then, two capsules should be taken once daily for a total of 10 days.
After hip replacement surgery
Treatment with Daroxomb should begin with one capsule taken 1 to 4 hours after completion of the surgical procedure. Then, two capsules should be taken once daily for a total of 28 to 35 days.
Prevention of thromboembolic events in blood vessels of the brain and body by preventing formation of clots resulting from abnormal heart function, and treatment of blood clots in leg veins and lungs, as well as prevention of recurrence of such clots
The recommended dose is 300 mg taken as one 150 mg capsule twice daily.
In patients aged 80 years or older, the recommended dose is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medications containing verapamil should receive Daroxomb at a reduced dose of 220 mg taken as one 110 mg capsule twice daily due to the potential increased risk of bleeding.
In patients with potentially increased risk of bleeding, the doctor may recommend treatment with Daroxomb at a dose of 220 mg taken as one 110 mg capsule twice daily.
Treatment with this medicine may be continued if the patient requires restoration of normal heart function by a procedure called cardioversion. Daroxomb should be taken as directed by the doctor.
In patients undergoing implantation of a medical device (stent) into a blood vessel to maintain its patency using a procedure called percutaneous coronary intervention with stent implantation, treatment with Daroxomb may be initiated once the doctor has confirmed adequate control of blood coagulation. Daroxomb should be taken as directed by the doctor.
Treatment of blood clots and prevention of recurrent blood clots in children
Daroxomb should be taken twice daily, one dose in the morning and one 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 and may adjust the dose during treatment. All other medications should be continued unless the doctor advises otherwise.
Table 1 shows the single and total daily doses of Daroxomb in milligrams (mg).
Doses depend on the patient's body weight in kilograms (kg) and age in years.
Table 1: Dosage table for Daroxomb capsules

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

How to take Daroxomb
Daroxomb 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 Daroxomb capsules from the blister pack.

Separate the single dose along the perforated line.
Peel back the protective foil from the blister and remove the capsule.

• Do not push the capsules through the blister foil.
• Do not peel back the foil until the capsule is needed.

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

Taking more Daroxomb than prescribed
Taking too high a dose of this medicine increases the risk of bleeding. If a patient has taken too many
capsules, contact a doctor immediately. Specific treatment methods are available.

Missed dose of Daroxomb
Prevention of blood clots after hip or knee replacement surgery
Continue taking the missed daily dose of Daroxomb at the usual time on the next day. Do not take a double dose to make up for a missed dose.

Use in adults: Prevention of thromboembolism in blood vessels of the brain and body by preventing formation of blood clots caused by abnormal heart function, and treatment of blood clots in the veins of legs and lungs, as well as prevention of recurrence of blood clots in veins of legs and lungs.
Use in children: Treatment of blood clots and prevention of recurrent blood clots.

A missed dose may be taken up to 6 hours before the next scheduled dose.
If less than 6 hours remain before the next scheduled dose, the missed dose should not be taken.
Do not take a double dose to make up for a missed dose.

Stopping Daroxomb treatment
Daroxomb should be taken as directed by the doctor. Do not stop taking this medicine without first consulting your doctor, as the risk of developing blood clots may be higher if treatment is stopped prematurely. Contact your doctor if gastrointestinal discomfort occurs after taking Daroxomb.

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.
Daroxomb affects the blood clotting system, therefore most adverse reactions are related to symptoms such as bruising or bleeding. Severe or profuse bleeding may occur, which is the most serious adverse reaction, and regardless of location, may lead to disability, be life-threatening, or even result in death. In some cases, such bleeding 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), contact your doctor immediately. Your doctor may decide to place you under close monitoring or change your treatment.
In case of a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

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

Prevention of blood clots after hip or knee replacement surgery
Common (may affect up to 1 in 10 people):

• Decrease in haemoglobin levels in 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 pink or red urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into a joint, following trauma or after a surgical procedure
• Formation of haematomas or bruising occurring after surgical procedure
• Blood in stool detected in laboratory tests
• Decrease in number of red blood cells in blood
• Decrease in blood cell count
• Allergic reaction
• Vomiting
• Frequent passage of loose or liquid stools
• Nausea
• Presence of discharge from wound (oozing of fluid from surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver disease or blood disorders

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

• Bleeding
• Bleeding may occur into the brain, from the surgical incision site, from the injection site or from the site of intravenous catheter insertion
• Blood-tinged discharge from the site of intravenous catheter insertion
• Coughing up blood or blood-tinged sputum
• Decrease in number of platelets in blood
• Decrease in number of red blood cells in blood after surgical procedure
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash consisting of dark red, raised, itchy bumps due to 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)
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Discharge of fluid from wound
• Discharge of fluid from surgical wound

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

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

Prevention of blood clots in the brain and other parts of the body by preventing formation of clots due to abnormal heart function

Common (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 pink or red urine due to presence of blood), or under the skin
• Decrease in number of red blood cells in blood
• Abdominal pain or stomach pain
• Indigestion
• Frequent passage of loose or liquid stools
• Nausea

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

• Bleeding
• Bleeding may occur from haemorrhoids, from the rectum or into the brain
• Formation of haematomas
• Coughing up blood or blood-tinged sputum
• Decrease in number of platelets in blood
• Decrease in haemoglobin levels in 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

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

• Bleeding may occur into a joint, from the surgical incision site, from a wound, from the 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 consisting of dark red, raised, itchy bumps due to 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 number or even absence of white blood cells (which help fight infections)
• Hair loss

In clinical trials, the number of heart attacks with dabigatran etexilate was numerically higher 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 lungs

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

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

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

• Bleeding
• Bleeding may occur into a joint or following trauma
• Bleeding may occur from haemorrhoids
• Decrease in number of red blood cells in blood
• Formation of haematomas
• Coughing up blood or blood-tinged 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 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 the surgical incision site, injection site or site of intravenous catheter insertion, or bleeding from the brain
• Decrease in number of platelets in blood
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash consisting of dark red, raised, itchy bumps due to allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decrease in haemoglobin levels in blood (a substance in red blood cells)
• Decrease in blood cell count
• Decrease in number 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 with dabigatran etexilate was numerically higher 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 recurrent blood clots in children

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

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

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

• Decrease in number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, into the brain, from the rectum, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in haemoglobin levels in blood (a substance in red blood cells)
• Decrease in blood cell count
• Itching
• Coughing up blood or blood-tinged 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 the surgical incision site, from the injection site or from the site of intravenous catheter insertion
• Bleeding may occur from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

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 of 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 or its representative in Poland.
By reporting adverse reactions, additional information on the safety of this medicine can be collected.

5. How to store Daroxomb

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or bottle following: EXP.
The expiry date refers to the last day of the stated month.
Do not store above 30°C. Store in the original packaging to protect from moisture.
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Daroxomb contains

• The active substance is dabigatran. Each hard capsule contains 126.83 mg of dabigatran etexilate (as mesilate), equivalent to 110 mg of dabigatran etexilate.
• The other ingredients are: tartaric acid, gum arabic, hypromellose 2910 (15 cps), dimethicone 350, talc and hydroxypropylcellulose (100 cps).
• The capsule shell contains carrageenan, potassium chloride, titanium dioxide (E 171), indigo carmine (E 132) and hypromellose 2910 (6 cps).

What Daroxomb looks like and contents of the pack
Daroxomb 110 mg is a size 1, blue, hard capsule filled with pellets ranging in colour from off-white to pale yellow.
Daroxomb is available in packs containing:
10 x 1, 30 x 1 or 60 x 1 hard capsules in single-dose perforated blisters made of
Aluminium/OPA/Aluminium/PVC foil.
A multipack containing 3 packs of 60 x 1 hard capsules (180 hard capsules)
or a multipack containing 2 packs of 50 x 1 hard capsules (100 hard capsules)
in single-dose perforated blisters made of Aluminium/OPA/Aluminium/PVC foil.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.,
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturers
Galenicum Health, S.L.U.
Sant Gabriel 50
08950 Esplugues de Llobregat, Barcelona
Spain
SAG Manufacturing, S.L.U.
Carretera Nacional 1 Km 36
28750 San Agustin de Guadalix, Madrid
Spain

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00