Dabigatran etexilate Krka 110 mg hard capsules EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Dabigatrán etexilato Krka 110mg hard capsules EFG

Read the entire leaflet carefully before you start 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

This medicine contains the active substance dabigatran etexilate and belongs to a group of medicines called anticoagulants. It works by blocking a substance in the body involved in blood clot formation.

Dabigatran etexilate is used in adults for:

• preventing the formation of blood clots in the veins following knee or hip replacement surgery.

• preventing the formation of blood clots in the brain (stroke) and in other blood vessels of the body if you have a type of irregular heart rhythm called non-valvular atrial fibrillation and have at least one additional risk factor.

• treating blood clots in the veins of your legs and lungs and to prevent recurrence of blood clots in the veins of your legs and lungs.

Dabigatran etexilate is used in children for:

• treating blood clots and preventing the recurrence of blood clots.

2. What you need to know before taking Dabigatrán etexilato Krka

Do not take Dabigatrán etexilato Krka

• if you are allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6).
• if your kidney function is severely reduced.
• if you are currently experiencing bleeding.
• if you have a disease in an organ of your body that increases the risk of serious bleeding (e.g., stomach ulcer, brain injury or hemorrhage, recent brain or eye surgery).
• if you are prone to bleeding. This tendency may be congenital, of unknown cause, or caused by other medicines.
• if you are taking medicines to prevent blood clots (e.g., warfarin, rivaroxaban, apixaban, or heparin), except when switching anticoagulant therapy, while you have a venous or arterial catheter and heparin is administered through this catheter to keep it open, or while your normal heart rhythm is being restored by a procedure called catheter ablation for atrial fibrillation.
• if your liver function is severely impaired or you have a liver disease that could be life-threatening.
• if you are taking oral ketoconazole or itraconazole, medicines used to treat fungal infections.
• if you are taking oral cyclosporine, a medicine used to prevent organ rejection after transplantation.
• if you are taking dronedarone, a medicine used to treat abnormal heart rhythm.
• if you are taking a combination product of glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C.
• if you have had an artificial heart valve implanted that requires lifelong anticoagulant treatment.

Warnings and precautions

Talk to your doctor before starting to take this medicine. During treatment with this medicine, you may also need to consult your doctor if you experience any symptoms or if you are scheduled for surgery.

Tell your doctor if you have or have had any disorder or illness, especially any of the following:

• If you have an increased risk of bleeding, for example:

• if you have recently had bleeding.

• if you have undergone surgical tissue removal (biopsy) within the last month.

• if you have suffered a serious injury (e.g., bone fracture, head injury, or any injury requiring surgical treatment).

• if you have inflammation of the esophagus or stomach.

• if you have gastroesophageal reflux (acid reflux into the esophagus).

• if you are receiving medicines that may increase the risk of bleeding. See “Other medicines and Dabigatrán etexilato Krka” below.

• if you are using anti-inflammatory medicines such as diclofenac, ibuprofen, or piroxicam.

• if you have an infection in the heart (bacterial endocarditis).

• if you know you have reduced kidney function or if you are dehydrated (symptoms include feeling thirsty and passing small amounts of dark [concentrated]/foamy urine).

• if you are over 75 years old.

• if you are an adult and weigh 50 kg or less.

• only if used in children: if the child has an infection in or around the brain.

• If you have had a heart attack or have been diagnosed with conditions that increase the risk of having a heart attack.

• If you have a liver disease associated with changes in blood tests. The use of this medicine is not recommended in such cases.

Take special care with Dabigatrán etexilato Krka

• If you need to undergo surgery:

In this case, this medicine should be temporarily stopped due to an increased risk of bleeding during and shortly after surgery. It is very important that you take this medicine exactly at the times instructed by your doctor, both before and after surgery.

• If surgery involves placement of a catheter or injection into the spine (e.g., for epidural or spinal anesthesia or pain relief):

• It is very important that you take this medicine exactly at the times instructed by your doctor, both before and after the procedure.

• Inform your doctor immediately if you experience numbness or weakness in the legs or bowel or bladder problems after the anesthesia wears off, as this requires urgent medical attention.

• If you fall or get injured during treatment, especially if you hit your head. Seek urgent medical help. You may need to be examined by a doctor, as you may have an increased risk of bleeding.

• If you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor so they can decide whether your treatment needs to be adjusted.

Other medicines and Dabigatrán etexilato Krka

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. In particular, you must inform your doctor before taking dabigatran etexilate if you are taking any of the following medicines:

• Medicines to reduce blood clotting (e.g., warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid).
• Medicines for fungal infections (e.g., ketoconazole, itraconazole), except when applied only to the skin.
• Medicines used to treat abnormal heart rhythm (e.g., amiodarone, dronedarone, quinidine, verapamil).

If you are taking medicines containing amiodarone, quinidine, or verapamil, your doctor may instruct you to use a reduced dose of this medicine depending on the condition for which it has been prescribed. See section 3.

• Medicines to prevent organ rejection after transplantation (e.g., tacrolimus, cyclosporine).
• A combination product of glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C).
• Anti-inflammatory and pain-relieving medicines (e.g., acetylsalicylic acid, ibuprofen, diclofenac).
• St. John’s wort, a herbal remedy for depression.
• Antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.
• Rifampicin or clarithromycin (two antibiotics).
• Antiviral medicines for HIV (e.g., ritonavir).
• Certain medicines used to treat epilepsy (e.g., carbamazepine, phenytoin).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

The effects of this medicine on pregnancy and the fetus are unknown. You should not use this medicine during pregnancy unless your doctor tells you it is safe to do so. If you are of childbearing age, you should avoid becoming pregnant while being treated with this medicine.

Breastfeeding is not recommended during treatment with this medicine.

Driving and using machines

This medicine has no known effects on the ability to drive or operate machinery.

3. How to take Dabigatran etexilate Krka

This medicine can be used in adults and children aged 8 years or older who are able to swallow the capsules whole. There are other age-appropriate pharmaceutical forms available for the treatment of children under 8 years of age.

Always follow exactly the instructions for use of this medicine as given by your doctor. If you are unsure, consult your doctor again.

Take dabigatran etexilate as recommended for the following situations:

Prevention of blood clots after knee or hip replacement surgery

The recommended dose is 220 mg once daily (administered as 2 capsules of 110 mg).

If your renal function is reduced by more than half or if you are 75 years of age or older, the recommended dose is 150 mg once daily (administered as 2 capsules of 75 mg).

If you are taking medications containing amiodarone, quinidine, or verapamil, the recommended dose is 150 mg once daily (administered as 2 capsules of 75 mg).

If you are taking medications containing verapamil and your renal function is reduced by more than half, you should be prescribed a reduced dose of this medicine of 75 mg, because your risk of bleeding may increase.

In both types of surgery, treatment must not be started if there is bleeding at the surgical site. If treatment cannot be initiated until the day after surgery, dosing should begin with 2 capsules once daily.

After knee replacement surgery

You should start treatment with this medicine 1–4 hours after surgery, taking one single capsule. Afterwards, take 2 capsules once daily for a total of 10 days.

After hip replacement surgery

You should start treatment with this medicine 1–4 hours after surgery, taking one single capsule. Afterwards, take 2 capsules once daily for a total of 28–35 days.

Prevention of stroke or systemic embolism due to blood clots caused by abnormal heart rhythm, and treatment of blood clots in the veins of your legs and lungs, including prevention of recurrence of such clots

The recommended dose is 300 mg, administered as one 150 mg capsule twice daily.

If you are 80 years of age or older, the recommended dose is 220 mg, administered as one 110 mg capsule twice daily.

If you are taking medications containing verapamil, you should be prescribed a reduced dose of this medicine of 220 mg, taken as one 110 mg capsule twice daily, because your risk of bleeding may increase.

If you have a potentially higher risk of bleeding, your doctor may decide to prescribe you a dose of 220 mg, administered as one 110 mg capsule twice daily.

You may continue taking this medicine if it is necessary to restore your normal heart rhythm through a procedure called cardioversion. Take this medicine exactly as instructed by your doctor.

If you have had a medical device (vascular stent) implanted in a blood vessel to keep it open during a procedure known as percutaneous coronary intervention with stent placement, you may receive treatment with this medicine once your doctor has determined that normal blood coagulation control has been achieved. Take this medicine exactly as instructed by your doctor.

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

This medicine should be taken twice daily, one dose in the morning and one dose in the evening, approximately at the same time each day. The dosing interval should be as close as possible to 12 hours.

The recommended dose depends on body weight and age. Your doctor will determine the correct dose. Your doctor may adjust your dose during treatment. Continue taking all other medications unless your doctor tells you to stop.

Table 1 shows the single doses and total daily doses of this medicine in milligrams (mg). The doses depend on the patient's weight in kilograms (kg) and age in years:

Table 1: Dosing table for dabigatran etexilate capsules

Weight/Age Combinations	Single Dose in mg	Total Daily Dose in mg
Weight in kg	Age in years
11 to less than 13 kg	8 to less than 9 years	75	150
13 to less than 16 kg	8 to less than 11 years	110	220
16 to less than 21 kg	8 to less than 14 years	110	220
21 to less than 26 kg	8 to less than 16 years	150	300
26 to less than 31 kg	8 to less than 18 years	150	300
31 to less than 41 kg	8 to less than 18 years	185	370
41 to less than 51 kg	8 to less than 18 years	220	440
51 to less than 61 kg	8 to less than 18 years	260	520
61 to less than 71 kg	8 to less than 18 years	300	600
71 to less than 81 kg	8 to less than 18 years	300	600
81 kg or more	10 to less than 18 years	300	600

Single doses requiring combinations of more than one capsule:

300 mg: two 150 mg capsules or
four 75 mg capsules

260 mg: one 110 mg capsule plus one 150 mg capsule or
one 110 mg capsule plus two 75 mg capsules

220 mg: two 110 mg capsules

185 mg: one 75 mg capsule plus one 110 mg capsule

150 mg: one 150 mg capsule or
two 75 mg capsules

How to take Dabigatran etexilate Krka

This medicine can be taken with or without food. The capsule should be swallowed whole with a glass of water to ensure release in the stomach. Do not break, chew, or open the capsule to take only its contents, as this may increase the risk of bleeding.

Instructions for opening the blister packs

The following images illustrate how to remove the capsules of this medicine from the blister:

To remove the capsule from the blister:

1. Hold the blister by the edges and separate one unit from the rest of the blister by gently tearing along the perforated line marking that unit.
2. Pull the edge of the foil until it is completely detached.
3. Allow the capsule to fall into your hand.
4. Swallow the capsules whole with a glass of water.

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

Switching anticoagulant treatment

Do not change your anticoagulant treatment without specific instructions from your doctor.

If you take more Dabigatran etexilate Krka than you should

Taking too much of this medicine increases the risk of bleeding. Contact your doctor immediately if you have taken too many capsules. Specific treatment options are available.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at: 915620420, indicating the medicine and the amount ingested.

If you forget to take Dabigatran etexilate Krka

Prevention of blood clots after knee or hip replacement surgery

Take the remaining daily doses of this medicine at the usual time on the following day.

Do not take a double dose to make up for a missed dose.

Use in adults: Prevention of stroke or systemic embolism due to blood clots caused by abnormal heart rhythm, and treatment of blood clots in the veins of the legs and lungs, including prevention of recurrence of such clots.

Use in children: Treatment of blood clots and prevention of recurrence of blood clots.

A missed dose may be taken up to 6 hours before the next scheduled dose.

A missed dose should be omitted if less than 6 hours remain before the next dose.

Do not take a double dose to make up for a missed dose.

If you stop taking Dabigatran etexilate Krka

Take this medicine exactly as prescribed. Do not stop treatment with this medicine without first consulting your doctor, as the risk of developing a blood clot may be higher if treatment is stopped too early. Contact your doctor if you experience indigestion after taking this medicine.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Serious adverse effects

This medicine affects blood clotting; therefore, most adverse effects are related to signs such as bruising or bleeding. Major or severe bleeding episodes may occur, which constitute the most serious adverse effects and, regardless of their location, may lead to disability, be potentially life-threatening, or even result in death. In some cases, this bleeding may not be obvious.

If you experience any bleeding that does not stop on its own, or if you experience signs of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), consult your doctor immediately. Your doctor may decide to keep you under close observation or change your medication.

Inform your doctor immediately if you experience a severe allergic reaction causing difficulty breathing or dizziness.

Other adverse effects

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

Prevention of blood clots after knee or hip replacement surgery

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

• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Abnormalities in liver function tests

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

• Bleeding may occur from the nose, stomach or intestine, penis/vagina, or urinary tract (including blood in urine turning urine pink or red), from hemorrhoids, rectum, under the skin, from a joint, or following an injury or surgery
• Formation of bruises or bruising after surgery
• Detection of blood in stool in a laboratory test
• Decrease in the number of red blood cells in the blood
• Decrease in the proportion of blood cells
• Allergic reaction
• Vomiting
• Frequent loose or watery stools
• Feeling nauseous
• Wound discharge (leakage of fluid from a surgical wound)
• Increased liver enzymes
• Yellowing of the skin or whites of the eyes, caused by liver or blood disorders

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

• Bleeding
• Bleeding may occur in the brain, at the site of a surgical incision, at the injection site, or at the site where a venous catheter is inserted
• Blood-tinged discharge from the site where a venous catheter is inserted
• Coughing up blood or sputum with blood streaks
• Decrease in the number of platelets in the blood
• Decrease in the number of red blood cells in the blood after surgery
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash with dark red, raised, itchy bumps due to an allergic reaction
• Sudden skin change affecting color and physical appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulcer)
• Inflammation of the esophagus and stomach
• Gastric juice reflux into the esophagus
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Fluid discharge from a wound
• Fluid discharge from a wound after surgery

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

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

Prevention of cerebral or systemic vascular blockage due to blood clots caused by abnormal heart rhythm

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

• Bleeding may occur from the nose, stomach or intestine, penis/vagina, urinary tract (including blood in urine turning urine pink or red), or under the skin
• Decrease in the number of red blood cells in the blood
• Abdominal pain or stomach pain
• Indigestion
• Frequent loose or watery stools
• Feeling nauseous

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

• Bleeding
• Bleeding may occur from hemorrhoids, rectum, or brain
• Bruising
• Coughing up blood or sputum with blood streaks
• Decrease in the number of platelets in the blood
• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Allergic reaction
• Sudden skin change affecting color and physical appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulcer)
• Inflammation of the esophagus and stomach
• Gastric juice reflux into the esophagus
• Vomiting
• Difficulty swallowing
• Abnormalities in liver function tests

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

• Bleeding may occur in a joint, at a surgical incision site, at a wound, at an injection site, or at the site where a venous catheter is inserted
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash with dark red, raised, itchy bumps due to an allergic reaction
• Decrease in the proportion of blood cells
• Increased liver enzymes
• Yellowing of the skin or whites of the eyes, caused by liver or blood disorders

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

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

In a clinical trial, the rate of heart attacks with this medicine was numerically higher than with warfarin. The overall incidence was low.

Treatment of blood clots in the veins of the legs and lungs, including prevention of recurrence of blood clots in the legs and/or lungs

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

• Bleeding may occur from the nose, stomach or intestine, rectum, penis/vagina, urinary tract (including blood in urine turning urine pink or red), or under the skin
• Indigestion

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

• Bleeding
• Bleeding may occur in a joint or wound
• Bleeding may occur from hemorrhoids
• Decrease in the number of red blood cells in the blood
• Bruising
• Coughing up blood or sputum with blood streaks
• Allergic reaction
• Sudden skin change affecting color and physical appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulcer)
• Inflammation of the esophagus and stomach
• Gastric juice reflux into the esophagus
• Feeling nauseous
• Vomiting
• Abdominal pain or stomach pain
• Frequent loose or watery stools
• Abnormalities in liver function tests
• Increased liver enzymes

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

• Bleeding may occur at a surgical incision site, at an injection site, at the site where a venous catheter is inserted, or 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 with dark red, raised, itchy bumps due to an allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Decrease in the proportion of blood cells
• Decrease in the number or even absence of leukocytes (which help fight infections)
• Yellowing of the skin or whites of the eyes, caused by liver or blood disorders
• Hair loss

In the clinical trial program, the rate of heart attacks with this medicine was higher than with warfarin. The overall incidence was low. No imbalance in the rate of heart attacks was observed in patients treated with dabigatran compared to patients treated with placebo.

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

Common (may affect 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 with dark red, raised, itchy bumps due to an allergic reaction
• Sudden skin change affecting color and physical appearance
• Bruising
• Nasal bleeding
• Gastric juice reflux into the esophagus
• Vomiting
• Feeling nauseous
• Frequent loose or watery stools
• Indigestion
• Hair loss
• Increased liver enzymes

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

• Decrease in the number of leukocytes (which help fight infections)
• Bleeding may occur in the stomach or intestine, brain, rectum, penis/vagina, urinary tract (including blood in urine turning urine pink or red), or under the skin
• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Decrease in the proportion of blood cells
• Itching
• Coughing up blood or sputum with blood streaks
• Abdominal pain or stomach pain
• Inflammation of the esophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowing of the skin or whites of the eyes, caused by liver or blood disorders

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

• Absence of leukocytes (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 in a joint or wound, at a surgical incision, at an injection site, or at the site where a venous catheter is inserted
• Bleeding may occur from hemorrhoids
• Stomach or intestinal ulcer (including esophageal ulcer)
• Abnormalities in liver function tests

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Dabigatran etexilate Krka

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the packaging and on the aluminium blister after EXP. The expiry date is the last day of the month indicated.

Store in the original packaging to protect from light and moisture.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at a SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Dabigatran etexilate Krka

• The active substance is dabigatran etexilate. Each hard capsule contains 110 mg of dabigatran etexilate (as dabigatran etexilate mesilate).
• The other components inside the capsule are tartaric acid, hypromellose, hydroxypropylcellulose and talc.
• The capsule components are titanium dioxide (E171), indigo carmine (E132), carrageenan, potassium chloride and hypromellose.
• The black printing ink contains shellac, black iron oxide (E172) and potassium hydroxide.

Appearance of the product and contents of the pack

Hard capsules (capsules): The capsule cap and body are both blue, with the mark “110” printed in black longitudinally. The capsule size is 1, approximately 19 mm in length.

Dabigatran etexilate Krka is available in packs containing:

• 10 x 1, 30 x 1, 60 x 1 hard capsules in unit dose blisters.

with a desiccant-containing stopper.

Marketing Authorisation Holder and Manufacturer Responsible

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Further information on this medicinal product is available by contacting the local representative of the Marketing Authorisation Holder:

KRKA Farmacéutica, S.L., C/ Anabel Segura 10, Pta. Baja, Oficina 1, 28108 Alcobendas, Madrid, Spain

Date of the most recent approval of this package leaflet: February 2024

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/.