Dabigatran etexilate Combix 110 mg hard capsules EFG: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Dabigatran etexilate Combix 110 mg hard capsules EFG

dabigatran etexilate

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 effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

What Dabigatran etexilate Combix is and what it is used for
What you need to know before taking Dabigatran etexilate Combix
How to take Dabigatran etexilate Combix
Possible side effects
How to store Dabigatran etexilate Combix
Contents of the pack and other information

1. What Dabigatrán etexilato Combix is and what it is used for

Dabigatrán etexilato Combix contains the active substance dabigatrán etexilato and belongs to a group of medicines called anticoagulants. It works by blocking a substance in the body involved in blood clot formation.

Dabigatrán etexilato Combix is used in adults to:

prevent the formation of blood clots in the veins following knee or hip replacement surgery.
prevent the formation of blood clots in the brain (stroke) and in other blood vessels in the body if you have a type of irregular heartbeat called non-valvular atrial fibrillation and have at least one additional risk factor.
treat blood clots in the veins of your legs and lungs, and to prevent the recurrence of blood clots in the veins of your legs and lungs.

Dabigatrán etexilato Combix is used in children to:

treat blood clots and prevent the recurrence of blood clots.

2. What you need to know before starting Dabigatrán etexilato Combix

Do not take Dabigatrán etexilato Combix

if you are allergic to dabigatran etexilate or to any of the other ingredients of this medicine (listed in section 6).
if your kidney function is severely reduced.
if you currently have bleeding.
if you have a disease in an organ of the body that increases the risk of serious bleeding (e.g., stomach ulcer, brain injury or bleeding, 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 between anticoagulant treatments, 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 reduced 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 Dabigatrán etexilato Combix. During treatment with this medicine, you may also need to consult your doctor if you experience any symptoms or if you need to undergo 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 (backflow of stomach juice into the esophagus).
- if you are receiving medicines that may increase the risk of bleeding. See “Other medicines and Dabigatrán etexilato Combix” 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. Use of this medicine is not recommended in this case.

Take special care with Dabigatrán etexilato Combix

If you need to undergo surgery:

In this case, Dabigatrán etexilato Combix should be temporarily stopped due to an increased risk of bleeding during and shortly after surgery. It is very important that you take Dabigatrán etexilato Combix before and after surgery exactly as directed by your doctor.

If surgery requires placement of a catheter or injection into the spine (e.g., for epidural or spinal anesthesia or for pain relief):
- It is very important that you take Dabigatrán etexilato Combix before and after surgery exactly as directed by your doctor.
- 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 situation requires urgent attention.
If you fall or are 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 Combix

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. In particular, you must tell your doctor before taking Dabigatrán etexilato Combix 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 treating fungal infections (e.g., ketoconazole, itraconazole), except if 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 advise you to take a reduced dose of Dabigatrán etexilato Combix depending on the condition for which it has been prescribed. See also section 3.

Medicines used 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 called selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors
Rifampicin or clarithromycin (two antibiotics)
Certain antiepileptic medicines (e.g., carbamazepine, phenytoin)

Pregnancy and breastfeeding

The effects of Dabigatrán etexilato Combix 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 Dabigatrán etexilato Combix.

Breastfeeding is not recommended during treatment with Dabigatrán etexilato Combix.

Driving and using machines

Dabigatrán etexilato Combix has no known effects on the ability to drive or use machines.

3. How to take Dabigatrán etexilato Combix

Dabigatrán etexilato Combix capsules can be used in adults and children aged 8 years or older who are able to swallow the capsules whole. Other age-appropriate pharmaceutical forms are available for the treatment of children under 8 years of age.

Follow exactly the dosing instructions for this medicine as given by your doctor. If in doubt, consult your doctor again.

Take Dabigatrán etexilato Combix as recommended for the following conditions:

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 Dabigatrán etexilato Combix of 75 mg, due to an increased risk of bleeding.

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

Begin treatment with Dabigatrán etexilato Combix 1-4 hours after surgery, taking one single capsule. Then take 2 capsules once daily for a total of 10 days.

After hip replacement surgery

Begin treatment with Dabigatrán etexilato Combix 1-4 hours after surgery, taking one single capsule. Then 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 Dabigatrán etexilato Combix of 220 mg taken as one 110 mg capsule twice daily, as 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 a procedure called cardioversion is performed to restore your normal heart rhythm. Take Dabigatrán etexilato Combix exactly as directed by your doctor.

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

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

Dabigatrán etexilato Combix 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 taking any of them.

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

Table 1: Dosing table for Dabigatrán etexilato Combix 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 Combix

Dabigatran Etexilate Combix capsules can be used in adults and children aged 8 years or older who are able to swallow the capsules whole.

Dabigatran Etexilate Combix 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.

Changing anticoagulant treatment

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

If you take more Dabigatran Etexilate Combix 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 telephone number: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Dabigatran Etexilate Combix

Prevention of blood clot formation after knee or hip replacement surgery: Take the remaining daily doses of Dabigatran Etexilate Combix at the usual time on the following day.

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

Use in adults: Prevention of systemic or cerebral vascular occlusion due to blood clot formation associated with irregular heartbeat, and treatment of blood clots in the veins of your legs and lungs, including prevention of recurrence of blood clots in the veins of your legs and lungs.

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

A missed dose can 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 missed doses.

If you stop taking Dabigatran Etexilate Combix

Take Dabigatran Etexilate Combix 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 Dabigatran Etexilate Combix.

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.

Dabigatran etexilate Combix acts on blood coagulation; therefore, most adverse effects are related to signs such as bruising or bleeding. Episodes of major or severe bleeding may occur, which represent 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, these bleedings may not be apparent.

If you experience any episode of 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.

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

Prevention of blood clot formation after knee or hip replacement surgery

Frequent (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 which may turn urine pink or red), from hemorrhoids, rectum, under the skin, from a joint, or at the site of injury or after 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 liquid 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 a surgical incision site, at an injection site, or at the site of a venous catheter insertion
Bloody discharge from the site of a venous catheter insertion
Coughing up blood or sputum with blood spots
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 caused by an allergic reaction
Sudden change in the skin affecting color and physical appearance
Itching
Ulcer in the stomach or intestine (including esophageal ulcer)
Inflammation of the esophagus and stomach
Reflux of gastric juice into the esophagus
Abdominal pain or stomach ache
Indigestion
Difficulty swallowing
Fluid leaking from a wound
Fluid leaking 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 stroke or systemic embolism due to blood clots caused by abnormal heart rhythm

Frequent (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 which may turn urine pink or red), or under the skin
Decrease in the number of red blood cells in the blood
Abdominal pain or stomach ache
Indigestion
Frequent loose or liquid 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 spots
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 change in the skin affecting color and physical appearance
Itching
Ulcer in the stomach or intestine (including esophageal ulcer)
Inflammation of the esophagus and stomach
Reflux of gastric juice 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 of a venous catheter insertion
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 caused by 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 Dabigatran etexilate Combix 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

Frequent (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 which may turn 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 spots
Allergic reaction
Sudden change in the skin affecting color and physical appearance
Itching
Ulcer in the stomach or intestine (including esophageal ulcer)
Inflammation of the esophagus and stomach
Reflux of gastric juice into the esophagus
Feeling nauseous
Vomiting
Abdominal pain or stomach ache
Frequent loose or liquid 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 of a venous catheter insertion, 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 caused by 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 Dabigatran etexilate Combix 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 in children

Frequent (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 caused by an allergic reaction
Sudden change in the skin affecting color and physical appearance
Bruising
Nasal bleeding
Reflux of gastric juice into the esophagus
Vomiting
Feeling nauseous
Frequent loose or liquid 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 which may turn 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 spots
Abdominal pain or stomach ache
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 site, at an injection site, or at the site of a venous catheter insertion
Bleeding may occur from hemorrhoids
Ulcer in the stomach or intestine (including esophageal ulcer)
Abnormalities in liver function tests

Reporting of adverse effects

If you experience any type of 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 Combix

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

Do not use this medicine after the expiry date stated on the carton, blister, or bottle after "EXP". The expiry date is the last day of the month indicated.

Aluminum – Aluminum (oPA/Al/PVC//Al blister): Do not store above 30°C.

Aluminum with desiccant liner – Aluminum (OPA/Al/PE//PE/Al/LDPE): No special storage conditions required.

Bottles: Do not store above 30°C. Keep in the original container to protect from moisture.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of unused medicines and their containers. This will help protect the environment.

6. Contents of the pack and other information

Composition of Dabigatran etexilate Combix

The active substance is dabigatran. Each hard capsule contains dabigatran etexilate mesilate equivalent to 110 mg of dabigatran etexilate.

The other components are:

Capsule contents: tartaric acid, hypromellose, hydroxypropylcellulose, talc.
Capsule shell: indigo carmine, carrageenan, potassium chloride, titanium dioxide, hypromellose.

Appearance of the product and contents of the pack

Hard capsules approximately 19.0 mm long with a bluish, opaque cap and a bluish, opaque "size 1" body, filled with whitish to yellowish granules.

The capsules are stored in blisters made of aluminum with a desiccant cover – aluminum (OPA/Al/PE//PE/Al/LDPE) and aluminum – aluminum (oPA/Al/PVC//Al blister), or in white plastic bottles with a silica gel desiccant in the lid (PP).

Pack sizes:

Blister packs containing: 10, 10x1 (single-dose blister), 30, 30x1 (single-dose blister), 60, 60x1 (single-dose blister), 100 or 180 hard capsules.

Bottles containing: 60 or 100 hard capsules.

Only certain pack sizes may be commercially available.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Laboratorios Liconsa S.A. Avenida Miralcampo 7 Poligono Industrial Miralcampo 19200, Azuqueca De Henares Guadalajara Spain

Date of the most recent review of this package leaflet:

March 2026

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