Dabigatran etexilate medreg

Package leaflet: Information for the patient

Dabigatran Etexilate Medreg, 110 mg, hard capsules
Dabigatranum etexilatum
Please read the entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• 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. The medicine may harm someone else, 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 Dabigatran Etexilate Medreg is and what it is used for
2. Important information before taking Dabigatran Etexilate Medreg
3. How to take Dabigatran Etexilate Medreg
4. Possible side effects
5. How to store Dabigatran Etexilate Medreg
6. Contents of the pack and other information

1. What Dabigatran Etexilate Medreg is and what it is used for

Dabigatran Etexilate Medreg 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 responsible for blood clotting.
Dabigatran Etexilate Medreg is used in adults to:

• prevent the formation of blood clots in veins after hip or knee replacement surgery.
• prevent 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 legs and lungs and to prevent recurrence of blood clots in the legs and lungs.

Dabigatran Etexilate Medreg is used in children to:

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

2. Important information before taking Dabigatran Etexilate Medreg

When not to take Dabigatran Etexilate Medreg

• 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 a disease of any internal organ which increases the risk of major bleeding (e.g. gastric ulcer, brain injury or intracranial haemorrhage, 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 where heparin is administered through the catheter to maintain patency, or during a catheter ablation procedure for atrial fibrillation to restore normal heart rhythm.
• if the patient has severe liver function impairment or liver disease which 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 ongoing anticoagulant therapy.

Warnings and precautions
Before starting treatment with Dabigatran Etexilate Medreg, 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 currently have or have had in the past 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 oesophagitis or gastritis.
• if the patient has gastro-oesophageal reflux (acid reflux into the oesophagus).
• if the patient is taking medicines which may increase the risk of bleeding. See below “Dabigatran Etexilate Medreg and other medicines”.
• if the patient is taking non-steroidal 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) or foamy urine).
• if the patient is over 75 years of age.
• if the patient is an adult with a body weight of 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 as 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 particular caution when taking Dabigatran Etexilate Medreg

• if the patient needs to undergo surgery: In such cases, temporary discontinuation of Dabigatran Etexilate Medreg is necessary due to the increased risk of bleeding during and immediately after surgery. It is very important to take Dabigatran Etexilate Medreg exactly as directed by the doctor both before and after surgery.
• if surgery involves insertion of a catheter or injection into the spine (e.g. for epidural or spinal anaesthesia or for pain relief):
• It is very important to take Dabigatran Etexilate Medreg exactly as directed by the doctor both before and after surgery.
• The patient should immediately inform the doctor if numbness or weakness in the legs or problems with bowel or bladder function occur after the anaesthesia wears off, as urgent medical care may be needed.
• if the patient falls or sustains an injury during treatment, especially if the head is injured. Immediate medical attention should be sought. 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 a change in treatment is necessary.

Dabigatran Etexilate Medreg and 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 Dabigatran Etexilate Medreg, 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 medicines are applied topically to the skin only.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking medicines containing amiodarone, quinidine or verapamil, the doctor may recommend a lower dose of Dabigatran Etexilate Medreg depending on the condition for which the medicine has been prescribed. See section 3.
• Medicines used to prevent rejection of a transplanted organ (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-noradrenaline 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 Dabigatran Etexilate Medreg has on pregnancy or the unborn child. This medicine should not be taken during pregnancy unless the doctor considers it safe. Women of childbearing age should use effective contraception to prevent pregnancy while taking Dabigatran Etexilate Medreg.
Breastfeeding is not recommended during treatment with Dabigatran Etexilate Medreg.

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

3. How to take Dabigatran Etexilate Medreg

Dabigatran Etexilate Medreg capsules can be used in adults and children aged 8 years or older who are able to swallow capsules whole. Other formulations are available for treatment of children under 8 years of age.
This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor.
Take Dabigatran Etexilate Medreg exactly as recommended below:

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).
If renal function is 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 medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Dabigatran Etexilate Medreg is 150 mg once daily (taken as 2 capsules of 75 mg).
Patients taking medicines containing verapamil who also have reduced renal function by more than half should take a reduced dose of 75 mg of Dabigatran Etexilate Medreg due to an increased risk of bleeding.

Treatment should not be initiated if there is active bleeding at the surgical site. If treatment cannot be started by the day after surgery, it should be initiated with a dose of 2 capsules once daily.

After knee replacement surgery
Treatment with Dabigatran Etexilate Medreg should be started by taking one capsule 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
Treatment with Dabigatran Etexilate Medreg should be started by taking one capsule 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 other parts of the body by preventing clot formation due to irregular heart rhythm, and treatment and 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 is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medicines containing verapamil should receive Dabigatran Etexilate Medreg at a reduced dose of 220 mg taken as one 110 mg capsule twice daily due to a possible increased risk of bleeding.
In patients with potentially increased risk of bleeding, the doctor may prescribe 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 rhythm through a procedure called cardioversion. Dabigatran Etexilate Medreg should be taken exactly as directed by the doctor.

In patients undergoing implantation of a medical device (stent) into a blood vessel to keep it open, using a procedure called percutaneous coronary intervention with stent implantation, treatment with Dabigatran Etexilate Medreg may be initiated once the doctor has confirmed adequate control of blood coagulation. Dabigatran Etexilate Medreg should be taken exactly as directed by the doctor.

Treatment and prevention of recurrent blood clots in children
Dabigatran Etexilate Medreg 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 ideally be 12 hours.

The recommended dose depends on body weight and age. The doctor will determine the correct dose and may adjust it during treatment. Continue taking all other prescribed medicines unless your doctor advises otherwise.

Table 1 shows the single and total daily doses of Dabigatran Etexilate Medreg in milligrams (mg). Doses depend on the patient's body weight in kilograms (kg) and age in years.
Table 1: Dosing table for Dabigatran Etexilate Medreg

Single doses requiring 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 Dabigatran Etexilate Medreg
Dabigatran Etexilate Medreg capsules can be taken with or without food. The capsule should be swallowed whole with a glass of water to facilitate passage into the stomach. Do not break, chew, or empty the pellets from the capsule, as this may increase the risk of bleeding.

Instructions for opening blister packs
The following pictogram illustrates how to remove Dabigatran Etexilate Medreg capsules from the blister pack.

Detach the single dose along the perforated line.

Peel back the protective foil from the blister and remove the capsule.

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

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

Accidental overdose of Dabigatran Etexilate Medreg
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 Dabigatran Etexilate Medreg
Prevention of blood clots after hip or knee replacement surgery
Continue taking the missed daily dose of Dabigatran Etexilate Medreg at the usual time on the following day.
Do not take a double dose to make up for the missed dose.

Use in adults: Prevention of thromboembolic events in blood vessels of the brain and body by preventing clot formation due to irregular heart rhythm, and treatment and prevention of recurrence of blood clots in the veins of the 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 treatment with Dabigatran Etexilate Medreg
Dabigatran Etexilate Medreg should be taken exactly as prescribed by the doctor. Do not stop taking this medicine without first consulting your doctor, as the risk of developing a blood clot may be higher if treatment is stopped prematurely.

Contact your doctor if you experience gastrointestinal discomfort after taking Dabigatran Etexilate Medreg.

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 experiences them.
Dabigatran Etexilate Medreg affects the blood clotting system, therefore 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, may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.
If bleeding that does not stop spontaneously or symptoms of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling) occur, contact your doctor immediately. The doctor may decide to place the patient under close monitoring or change the treatment.
In case of a severe allergic reaction, which may cause difficulty in 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 occur in up to 1 in 10 people):

• Decreased haemoglobin concentration in blood (a substance present in red blood cells)
• Abnormal liver function test results

Uncommon (may occur in 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-coloured urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into joints, following injury or after surgery
• Formation of haematomas or bruises following surgery
• Blood in stool detected in laboratory tests
• Decreased number of red blood cells in blood
• Reduced proportion of blood cells (decreased haematocrit)
• Allergic reaction
• Vomiting
• Frequent passage of loose or watery stools
• Nausea
• Discharge from wound (fluid oozing from surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver disease or blood disorders

Rare (may occur in 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-stained sputum
• Decreased platelet count in blood
• Decreased number of red blood cells in blood after surgery
• Severe allergic reaction causing difficulty in breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash consisting of dark red, raised, itchy bumps due to an 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

Not known (frequency cannot be estimated from available data):

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

Prevention of blood clots in blood vessels of the brain and body by preventing formation of clots caused by 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/vagina or urinary tract (including pink or red-coloured urine due to presence of blood), or under the skin
• Decreased number of red blood cells in 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 haematomas
• Coughing up blood or blood-stained sputum
• Decreased platelet count in blood
• Decreased haemoglobin concentration in blood (a substance present 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 occur in up to 1 in 1,000 people):

• Bleeding may occur into joints, 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 an allergic reaction
• Reduced proportion of blood cells (decreased haematocrit)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver disease or blood disorders

Not known (frequency cannot be estimated from available data):

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

In clinical studies, the number of heart attacks was numerically higher with Dabigatran Etexilate Medreg 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 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/vagina or urinary tract (including pink or red-coloured 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 joints or following injury
• Bleeding may occur from haemorrhoids
• Decreased number of red blood cells in blood
• Formation of 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
• Increased liver enzyme activity

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

• Bleeding may occur from the surgical incision site, from the injection site, from the site of intravenous catheter insertion, or into the brain
• Decreased platelet count 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 an allergic reaction
• Difficulty swallowing

Not known (frequency cannot be estimated from available data):

• Difficulty breathing or wheezing
• Decreased haemoglobin concentration in blood (a substance present in red blood cells)
• Reduced proportion of blood cells (decreased haematocrit)
• Decreased number or even absence of white blood cells (which help fight infections)
• Yellowing of the skin or whites of the eyes due to liver disease or blood disorders
• Hair loss

In clinical studies, the number of heart attacks was numerically higher with Dabigatran Etexilate Medreg 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 occur in up to 1 in 10 people):

• Decreased number of red blood cells in blood
• Decreased platelet count in blood
• Skin rash consisting of dark red, raised, itchy bumps due to an 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 watery stools
• Indigestion
• Hair loss
• Increased liver enzyme activity

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

• Decreased number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, into the brain, from the anus, from the penis/vagina or urinary tract (including pink or red-coloured urine due to presence of blood), or under the skin
• Decreased haemoglobin concentration in blood (a substance present in red blood cells)
• Reduced proportion of blood cells (decreased haematocrit)
• 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 due to liver disease or blood disorders

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 joints, from wounds, 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 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, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181 C 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 this medicine.

5. How to store Dabigatran Etexilate Medreg

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack after:
"Expiry date (EXP)" or "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 help protect the environment.

6. Contents of the pack and other information

What Dabigatran Etexilate Medreg 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 type 2910, dimethicone 350, talc and hydroxypropylcellulose.
• The capsule shell contains carrageenan, potassium chloride, titanium dioxide (E 171), hypromellose type 2910 and Indigocarmine (E 132).

What Dabigatran Etexilate Medreg looks like and contents of the pack
Dabigatran Etexilate Medreg 110 mg is a blue, hard capsule of size 1, filled with pellets ranging in colour from whitish to pale yellow.
This medicine is available in packs containing 10 × 1, 30 × 1 or 60 × 1 hard capsules, in perforated unit-dose blisters made of Aluminium/OPA/Aluminium/PVC, packed in a cardboard box.
A multipack containing 3 packs of 60 × 1 hard capsules (180 hard capsules) or 2 packs of 50 × 1 hard capsules (100 hard capsules) in perforated unit-dose blisters made of Aluminium/OPA/Aluminium/PVC, packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Medreg s.r.o.
Na Florenci 2116/15
Nové Město 110 00 Prague 1
Czech Republic
Tel.: (+420) 516 770 199

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 Agustín Del Guadalix
Madrid
Spain

This medicine is authorised for marketing in the European Economic Area under the following names:
Malta: Dabigatran Etexilate Medreg 110 mg hard capsules
Poland: Dabigatran Etexilate Medreg