Daroxomb

Package Leaflet: Information for the Patient

Daroxomb, 110 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 Package Leaflet

• 1. What is Daroxomb and what is it 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 is Daroxomb and what is it used for

Daroxomb 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.
Daroxomb is used in adults to:

• prevent the formation of blood clots in the veins after hip or knee replacement surgery.
• prevent the formation of 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 heart valve problems and at least one additional risk factor.
• treat blood clots in the veins of the legs and lungs and prevent the recurrence of blood clots in the veins of the legs and lungs.

Daroxomb is used in children to:

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

2. Important information before taking Daroxomb

When not to take Daroxomb

• 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 an 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 may be inherited, of unknown cause, or due to the use of other medications.
• if you are taking anticoagulant medications (e.g. warfarin, rivaroxaban, apixaban, or heparin), except when switching anticoagulant treatment, introducing a venous catheter or arterial line, when heparin is administered to maintain catheter patency or when restoring normal heart rhythm using a procedure called catheter ablation in atrial fibrillation.
• if you have severe liver impairment or liver disease that may 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 virus infection.
• if you have a prosthetic heart valve that requires ongoing anticoagulant treatment.

Warnings and precautions

Before starting treatment with Daroxomb, 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 esophagitis or gastritis.
• if you have gastroesophageal reflux disease.
• if you are taking medications that may increase the risk of bleeding. See "Daroxomb and other medications" below.
• if you are taking anti-inflammatory medications such as diclofenac, ibuprofen, piroxicam.
• if you have an infection of the heart (infective endocarditis).
• if you have reduced kidney function or are dehydrated (feeling thirsty and producing less urine, which is dark and concentrated).
• 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 the patient has been diagnosed with conditions that increase the risk of heart attack.
• if you have liver disease that affects blood test results. In such cases, the use of this medication is not recommended.

When to exercise special caution when taking Daroxomb

• if you need to undergo surgery: In this case, it is necessary to discontinue Daroxomb temporarily due to the increased risk of bleeding during and after surgery. It is very important to take Daroxomb before and after surgery exactly as prescribed by your doctor.
• if the surgical procedure requires the insertion of a catheter or injection into the spine (e.g. for epidural or spinal anesthesia or pain relief):
• It is very important to take Daroxomb before and after surgery exactly as prescribed by your doctor.
• You should immediately inform your doctor if you experience numbness or weakness in your lower limbs or problems with your bowels 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.

Daroxomb and other medications

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

• Anticoagulant medications (e.g. warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, aspirin).
• Medications used to treat fungal infections (e.g. ketoconazole, itraconazole), unless they are used only topically.
• 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 Daroxomb, depending on the condition for which it was prescribed. See 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 virus infection).
• Anti-inflammatory and pain-relieving medications (e.g. aspirin, ibuprofen, diclofenac).
• St. John's Wort, a herbal remedy 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 Daroxomb 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 Daroxomb.
Do not breastfeed while taking Daroxomb.

Driving and using machines

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

3. How to take Daroxomb

Daroxomb 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 medication should always be taken exactly as prescribed by your doctor. If you are unsure, consult your doctor.

Take Daroxomb as follows:

Prevention of blood clots after hip or knee replacement surgery
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 years or older, 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 Daroxomb is 150 mg once daily(taken as 2 capsules of 75 mg each).
Patients taking medications containing verapamilwith reduced kidney function (more than half reduced) should take a reduced dose of Daroxomb of 75 mgdue to the increased risk of bleeding.
In both types of surgery, do not start treatment if there is bleeding from the surgical site. If it is not possible to start treatment the day after surgery, start with a dose of 2 capsules once daily.
After knee replacement surgery
Start taking Daroxomb within 1 to 4 hours after the end of surgery. Then take 2 capsules once daily for a total of 10 days.
After hip replacement surgery
Start taking Daroxomb within 1 to 4 hours after the end of surgery. Then take 2 capsules 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 recurrence of blood clots in the legs and lungs
The recommended dose is 300 mgtaken as one 150 mg capsule twice daily.
In patients aged 80 years or older, the recommended dose is 220 mgtaken as one 110 mg capsule twice daily.
Patients taking medications containing verapamilshould receive a reduced dose of Daroxomb of 220 mgtaken as one 110 mg capsule twice dailydue to the potential increased risk of bleeding.
In patients with a potentially increased risk of bleeding, the doctor may recommend a dose of 220 mgtaken as one 110 mg capsule twice daily.
Treatment can be continued if the patient needs to restore normal heart rhythm using a procedure called cardioversion. Take Daroxomb as prescribed by your 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 Daroxomb treatment after the doctor has confirmed that blood clotting control has been achieved. Take Daroxomb as prescribed by your doctor.
Treatment of blood clots and prevention of recurrence of blood clots in children
Take Daroxomb 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 body weight and age. The doctor will determine the correct dose. The doctor may adjust the dose during treatment. Continue to take all other medications unless the doctor advises you to stop taking them.
Table 1 shows the single and total daily doses of Daroxomb in milligrams (mg). The doses depend on the patient's body weight in kilograms (kg) and age in years.
Table 1: Daroxomb Capsule Dosing Table

Doses requiring the 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:
two 110 mg capsules
185 mg:
one 75 mg capsule and one 110 mg capsule
150 mg:
one 150 mg capsule or
two 75 mg capsules

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 diagram shows how to remove Daroxomb capsules from the blister pack.

Separate a single dose from the blister pack along the perforated line.

Remove the protective foil from the blister pack and take out the capsule.

• Do not push the capsules through the blister pack foil.
• Do not remove the foil until the capsule is needed.

Changing anticoagulant medication

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

Taking more than the recommended dose of Daroxomb

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 Daroxomb

Prevention of blood clots after hip or knee replacement surgery
Continue taking the missed daily dose of Daroxomb at the same time the next day. Do not take a double dose to make up for the missed dose.
Use in adults: 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 recurrence of 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 treatment with Daroxomb

Daroxomb should be taken as prescribed 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 Daroxomb.
If you have any further questions about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, Daroxomb can cause side effects, although not everybody gets them.
Daroxomb affects the blood clotting system, so most side effects are related to symptoms such as bruising or bleeding. Major or severe 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 bleedings may not be visible.
If you experience bleeding that does not stop on its own or symptoms of excessive bleeding (exceptional weakness, fatigue, pallor, dizziness, headache, or unexplained swelling), contact your doctor immediately. Your doctor may decide to closely monitor you or change your medication.
If you experience a severe allergic reaction that can cause difficulty breathing or dizziness, contact your doctor immediately.
The following side effects are listed by frequency of occurrence:

• 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
• Formation of hematomas or bruising after surgery
• Blood in the stool as detected by laboratory tests
• Decreased red blood cell count
• Decreased hematocrit
• Allergic reaction
• Vomiting
• Frequent loose or liquid stools
• Nausea
• Wound secretion
• Increased liver enzyme activity
• Jaundice 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 site, from the injection site, or from the catheter insertion site
• Blood-tinged secretion from the catheter insertion site
• Coughing up blood or blood-tinged sputum
• Decreased platelet count
• Decreased red blood cell count after surgery
• 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 due to an allergic reaction
• Sudden change in skin color or appearance
• Itching
• Ulcer of the stomach or intestines (including esophageal ulceration)
• Esophagitis or gastritis
• Gastroesophageal reflux disease
• Abdominal pain or stomach pain
• Difficulty swallowing
• Wound secretion
• Frequency not known (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
• 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 into the brain
• Formation of hematomas
• 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
• Ulcer of the stomach or intestines (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 site, from the injection site, or from the 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 due to an allergic reaction
• Decreased hematocrit
• Increased liver enzyme activity
• Jaundice of the skin or whites of the eyes due to liver or blood disease
• Frequency not known (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 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 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
• Formation of hematomas
• Coughing up blood or blood-tinged sputum
• Allergic reaction
• Sudden change in skin color or appearance
• Itching
• Ulcer of the stomach or intestines (including esophageal ulceration)
• Esophagitis or gastritis
• Gastroesophageal reflux disease
• 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 the surgical site, from the injection site, or from the catheter insertion site or 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 due to an allergic reaction
• Difficulty swallowing
• Frequency not known (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 of the skin or whites of the eyes due to liver or blood disease
• Hair loss

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 due to an allergic reaction
• Sudden change in skin color or appearance
• Formation of hematomas
• Nosebleeds
• Gastroesophageal reflux disease
• 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 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 of the skin or whites of the eyes due to liver or blood disease
• Frequency not known (frequency cannot be estimated from the available data):
• Absence 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 the joint, from the wound, from the surgical site, from the injection site, or from the catheter insertion site
• Bleeding may occur from hematomas
• Ulcer of the stomach or intestines (including esophageal ulceration)
• 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 or pharmacist. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 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 or its representative in Poland.
Reporting side effects will help to gather more information on the safety of this medication.

5. How to store Daroxomb

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 bottle after EXP.
The expiry date refers to the last day of the month stated.
Do not store above 30°C. Store in the original package to protect from moisture.
Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications 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 mesylate) which corresponds to 110 mg of dabigatran etexilate.
• The other ingredients are: tartaric acid, arabic gum, 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 blue hard capsule, size 1, filled with pellets that are white to off-white in color.
Daroxomb is available in packs containing:
10 x 1, 30 x 1, or 60 x 1 hard capsules in perforated unit dose blisters of aluminum/OPA/aluminum/PVC.
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 perforated unit dose blisters of aluminum/OPA/aluminum/PVC.
Not all pack sizes may be marketed.

Marketing authorization holder

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

Manufacturer

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 about this medication, please contact the representative of the marketing authorization holder in Poland:

Zentiva Polska Sp. z o.o.
Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00

Date of last revision of the leaflet: