Daroxomb

Patient Information Leaflet

Daroxomb, 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 questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet Contents

1. What Daroxomb is and what it is used for
2. What you need to know 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 the active substance dabigatran etexilate 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.
Daroxomb is used in adults to:

• prevent the formation of blood clots in the brain (stroke) and in other blood vessels in the body in patients with 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 such clots.

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 injury 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, 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, the patient should discuss this with their doctor. If symptoms occur during treatment with this medicine or if the patient has undergone surgery, they should contact their doctor.
The patient should inform their doctor if they currently 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 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 (acid reflux into the esophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below "Daroxomb with other medicines".
• if the patient is taking nonsteroidal anti-inflammatory drugs (NSAIDs), 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 previously 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 cases, use of this medicine is not recommended.

When to exercise special caution when taking Daroxomb

• if the patient needs to undergo surgery: In such cases, 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 injection into the spinal canal (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 their doctor if they experience numbness or weakness in the lower limbs or problems with bowel or bladder function after the anesthesia wears off, as urgent medical care is required.
• if the patient falls or injures themselves during treatment, especially if they injure their head. Immediate medical attention should be sought. The doctor will assess whether there may be 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 a change in treatment is necessary.

Daroxomb with other medicines
The patient should inform their doctor or pharmacist about all medicines they are currently taking, have recently taken, or plan to take. In particular, the patient should inform their doctor before taking Daroxomb if they are 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 medicines 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 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 (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).
• 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 potential should avoid becoming pregnant while taking Daroxomb.
Breastfeeding should not be performed during treatment with Daroxomb.

Driving and operating machinery
Daroxomb has no effect or 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 pharmaceutical formulations are available for treating children under 8 years of age.
This medicine should always be taken as prescribed by the doctor. In case of doubt, consult your doctor.
Daroxomb should be taken as follows:
Prevention of blood clots in blood vessels of the brain and throughout the body by preventing clots that form due to abnormal heart function, and treatment of blood clots in the veins of the legs and lungs, as well as prevention of recurrent 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 above, the recommended dose of Daroxomb is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medicines containing verapamil should receive a reduced dose of Daroxomb of 220 mg taken as one 110 mg capsule twice daily due to a potentially increased risk of bleeding.
In patients with a potentially increased risk of bleeding, the doctor may recommend treatment with 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 through a procedure called cardioversion or through a procedure called catheter ablation for atrial fibrillation. Daroxomb should be taken as directed by the 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 treatment with Daroxomb, 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 dose in the evening, approximately at the same time each day. The interval between doses should ideally be 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. All other medications should continue to be taken 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: Dosing 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: as two capsules of 110 mg
185 mg: as one capsule of 75 mg and one capsule of 110 mg
150 mg: as one capsule of 150 mg or
two capsules of 75 mg

How to take Daroxomb
Daroxomb may 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 break, crush, or chew the
capsules, and do not 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 required dose from the blister 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.

Switching anticoagulant therapy
Do not switch anticoagulant therapy 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
A missed dose may be taken if there is still at least 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 blood clot formation 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 effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Daroxomb affects the blood clotting system, so most adverse effects involve symptoms such as bruising or bleeding. Severe or extensive bleeding may occur, which is the most serious adverse effect 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) appear, contact your doctor immediately. The doctor may decide to place the patient under close observation or change the treatment.
In the event of a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

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

Prevention of thromboembolism in blood vessels of the brain and body by preventing the formation of clots that occur due to abnormal 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/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 hemorrhoids, from the rectum, or into the brain
• Formation of bruises (hematomas)
• Coughing up blood or bloody sputum
• Decrease in the number of platelets in the blood
• Decrease in hemoglobin levels in the blood (a substance in red blood cells)
• Allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Inflammation of the esophagus and stomach
• Regurgitation of stomach contents into the esophagus (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 due to liver or blood disease

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 occurrences was small.

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

Common (may occur in 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 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 may occur from hemorrhoids
• Decrease in the number of red blood cells in the blood
• Formation of bruises (hematomas)
• Coughing up blood or bloody sputum
• Allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Inflammation of the esophagus and stomach
• Regurgitation of stomach contents into the esophagus (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, from an injection site, from the 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

Unknown frequency (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decrease in hemoglobin 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 due to liver or blood disease
• Hair loss

In clinical trials, the number of heart attacks was numerically higher with dabigatran etexilate than with warfarin. The overall number of occurrences was low. No difference in the number of heart attacks was observed between patients treated with dabigatran and patients 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 color and appearance
• Formation of bruises (hematomas)
• Nosebleeds
• Regurgitation of stomach contents into the esophagus (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, into the brain, from the rectum, from the penis or vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in hemoglobin levels in the blood (a substance in red blood cells)
• Decrease in blood cell count
• Itching
• Coughing up blood or bloody sputum
• Abdominal pain or stomach pain
• Inflammation of the esophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowing of the skin or whites of the eyes due to liver or blood disease

Unknown (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 may occur from hemorrhoids
• Stomach or intestinal ulcer (including esophageal ulceration)
• Abnormal liver function test results in laboratory tests

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions at 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 effects can also be reported to the marketing authorization holder or its representative in Poland. Reporting adverse effects helps to gather more information on the safety of the medicine.

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 blister pack 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 must not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required.
These measures 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 172.95 mg of dabigatran etexilate (as mesilate), equivalent to 150 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 (E171), indigo carmine (E132) and hypromellose 2910 (6 cps).

What Daroxomb looks like and contents of the pack
Daroxomb 150 mg is a hard capsule with a blue cap and a body ranging from white to off-white, size 0, filled with pellets ranging from off-white to pale yellow in colour.
Daroxomb is available in packs containing
10 x 1, 30 x 1 or 60 x 1 hard capsule in single-dose perforated blisters made of
Aluminium/OPA/Aluminium/PVC foil.
A multipack containing 3 packs of 60 x 1 hard capsule (180 hard capsules)
or a multipack containing 2 packs of 50 x 1 hard capsule (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
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 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