Package Insert:Information for the Patient

Dabigatrán etexilate Combix150 mg Hard Capsules EFG

dabigatrán etexilate

Read this package insert carefully before starting to take this medication,because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

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

Dabigatrán etexilato Combix is used in adults for:

• 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.

• treat blood clots in the veins of your legs and lungs and to prevent new blood clots from forming in the veins of your legs and lungs.

Dabigatrán etexilato Combix is used in children for:

• treat blood clots and to prevent new blood clots from forming.

Do not take Dabigatrán etexilato Combix

• if you are allergic to dabigatrán etexilato or 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 any disease in an organ of the body that increases the risk of severe bleeding (e.g., stomach ulcer, injury or bleeding in the brain, recent surgical intervention in the brain or eyes).
• 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 clotting in the blood (e.g., warfarin, rivaroxabán, apixabán or heparin), except when changing from one anticoagulant treatment to another, while having 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 if you have any liver disease that may be fatal.
• if you are taking ketoconazol oral or itraconazol, medicines used in the treatment of fungal infections.
• if you are taking ciclosporina oral, a medicine used to prevent organ rejection after a transplant.
• if you are taking dronedarona, 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 permanent anticoagulant treatment.

Warnings and precautions

Consult your doctor before starting to take Dabigatrán etexilato Combix. During treatment with this medicine, you may also need to consult your doctor if you experience any symptoms or if you are to undergo surgery.

Inform your doctorif you have or have had any disorder or disease, especially any of the following:

• If you have an increased risk of bleeding, for example:
• • if you have recently had bleeding.
  • if you have had a surgical tissue extraction (biopsy) in the last month.
  • if you have had a severe injury (e.g., a bone fracture, a head injury, or any injury that required surgical treatment).
  • if you have inflammation of the esophagus or stomach.
  • if you have problems with reflux of stomach acid into the esophagus.
  • if you are taking medicines that may increase the risk of bleeding. See “Other medicines and Dabigatrán etexilato Combix below.
  • if you are taking anti-inflammatory medicines such as diclofenaco, ibuprofeno, or piroxicam.
  • if you have a bacterial infection of the heart (endocarditis).
  • if you know that you have reduced kidney function or if you are dehydrated (symptoms include feeling thirsty and passing small amounts of dark-colored, concentrated urine with foam).
  • 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 the brain or around it.

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

• if you have liver disease associated with changes in blood tests. The use of this medicine is not recommended in this case.

Be especially careful with Dabigatrán etexilato Combix

• if you have to undergo surgery:

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

• if a surgical procedure requires the placement of a catheter or injection into the spinal column (e.g., for epidural or spinal anesthesia or for pain relief):
• • It is very important that you take Dabigatrán etexilato Combix exactly as instructed by your doctor before and after surgery.
  • Inform your doctor immediately if you experience numbness or weakness in your legs or intestinal or urinary problems after the end of anesthesia, as this situation requires urgent attention.
• if you fall or are injured during treatment, especially if you hit your head. Seek urgent medical attention. You may need to have a doctor examine you, as you may have an increased risk of bleeding.

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

Other medicines and Dabigatrán etexilato Combix

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.Particularly, inform your doctor before taking Dabigatrán etexilato Combix if you are taking any of the following medicines:

• Medicines to reduce blood clotting (e.g., warfarin, fenprocumón, acenocumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxabán, ácido acetilsalicílico)
• Medicines used in the treatment of fungal infections (e.g., ketoconazol, itraconazol), except when applied to the skin
• Medicines used in the treatment of abnormal heart rhythm (e.g., amiodarona, dronedarona, quinidina, verapamilo)

If you are taking medicines that contain amiodarona, quinidina, or verapamilo, your doctor may instruct you to use a reduced dose of Dabigatrán etexilato Combix according to the disease for which you have been prescribed it. See also section 3.

• Medicines used to prevent organ rejection after a transplant (e.g., tacrólimus, ciclosporina)
• A combination product of glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C)
• Anti-inflammatory and pain-relieving medicines (e.g., ácido acetilsalicílico, ibuprofeno, diclofenaco)
• St. John's Wort, a medicinal herb for depression
• Antidepressant medicines called selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors
• Rifampicina or claritromicina (two antibiotics)
• Antiviral medicines for HIV (e.g., ritonavir)
• Certain medicines used to treat epilepsy (e.g., carbamazepina, fenitoína)

Pregnancy and breastfeeding

The effects of Dabigatrán etexilato Combix on pregnancy and the fetus are unknown. Do not use this medicine if you are pregnant unless your doctor tells you it is safe to do so. If you are of childbearing age, avoid becoming pregnant during treatment with Dabigatrán etexilato Combix.

Do not breastfeed naturally during treatment with Dabigatrán etexilato Combix.

Driving and operating machines

Dabigatrán etexilato Combix has no known effects on the ability to drive and operate machines.

Dabigatran etexilate Combix capsules can be used in adults and children aged 8 years or older who are able to swallow the capsules whole. There are other appropriate pharmaceutical forms for children under 8 years old.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

Take Dabigatran etexilate Combix as recommended for the following situations:

Prevention of vascular or systemic thrombosis developed after abnormal heart rhythm and treatment of blood clots in the veins of their legs and lungs, including prevention of blood clots in the veins of their legs and lungs from recurring

The recommended dose is 300 mg administered in the form ofone 150 mg capsule twice a day.

If you are80 years of age or older, the recommended dose is 220 mg administered in the form ofone 110 mg capsule twice a day.

If you are usingmedicines containing verapamil, you should be instructed on a reduced dose of Dabigatran etexilate Combix of 220 mg taken in the form ofone 110 mg capsule twice a day, as your risk of bleeding may increase.

If you have apotential higher risk of bleeding, your doctor may decide to prescribe a dose of 220 mg administered in the form ofone 110 mg capsule twice a day.

You can continue taking this medication if necessary to restore your normal heart rhythm through a procedure called cardioversion. Take Dabigatran etexilate Combix as instructed by your doctor.

If you have had a medical device (vascular endoprosthesis) placed in a blood vessel to keep it open in a procedure called percutaneous coronary intervention with vascular endoprosthesis placement, you can receive treatment with Dabigatran etexilate Combix once your doctor has decided that normal blood coagulation control has been achieved. Take Dabigatran etexilate Combix as instructed by your doctor.

Treatment of blood clots and prevention of blood clots from recurring in children

Dabigatran etexilate Combix should be taken twice a day, one dose in the morning and one dose in the evening, approximately at the same time every day. The administration interval should be as close as possible to 12 hours.

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

The table 1 shows the single doses and total daily doses of Dabigatran etexilate Combix 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 Combix capsules

Single doses requiring combinations of more than one capsule

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.

Change in 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 medication increases the risk of bleeding. Contact your doctor immediately if you have taken too many capsules. There are specific treatment options available.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Dabigatran etexilate Combix

Prevention of blood clots after knee or hip arthroplastyTake the remaining daily doses of Dabigatran etexilate Combix at the same time the next day.

Do not take a double dose to compensate for the missed doses.

Use in adults: Prevention of vascular or systemic thrombosis developed after abnormal heart rhythm and treatment of blood clots in the veins of their legs and lungs, including prevention of blood clots in the veins of their legs and lungs from recurring

Use in children: Treatment of blood clots and prevention of blood clots from recurring

Blood clots

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

A missed dose should be omitted if the remaining time before the next dose is less than 6 hours. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Dabigatran etexilate Combix

Take Dabigatran etexilate Combix exactly as prescribed. Do not interrupt your treatment with this medication without consulting your doctor first, as the risk of developing a blood clot may be higher if you interrupt treatment too soon. Contact your doctor if you experience indigestion after taking Dabigatran etexilate Combix.

If you have any other questions about the use of this medication, ask your doctor or pharmacist

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

Dabigatrán etexilato Combix acts on blood coagulation; therefore, most side effects are related to signs such as bruising or bleeding. Severe or life-threatening bleeding episodes, which can cause disability, may occur, regardless of their location. In some cases, these bleeding episodes may not be apparent.

If you experience any bleeding episode that does not stop on its own or if you experience signs of excessive bleeding (exceptional weakness, fatigue, pallor, 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 that causes difficulty breathing or dizziness.

The possible side effects are listed below, grouped by frequency of occurrence.

Prevention of cerebral or systemic vascular obstruction by blood clot formation developed after abnormal heart rhythm

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

• Bleeding may occur through the nose, stomach, or intestines, penis/vagina, or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Decreased red blood cell count in the blood
• Abdominal pain or stomach pain
• Indigestion
• Frequent loose or liquid stools
• Feeling like vomiting

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

• Bleeding
• Bleeding may occur from hemorrhoids, rectum, or brain
• Formation of hematomas
• Coughing up blood or sputum with blood spots
• Decreased platelet count in blood
• Decreased hemoglobin level in blood (the substance present in red blood cells)
• Allergic reaction
• Sudden change in skin that affects color and physical appearance
• Itching
• Ulcer in the stomach or intestines (including esophageal ulcer)
• Inflammation of the esophagus and stomach
• Reflex of stomach acid into the esophagus
• Vomiting
• Difficulty swallowing
• Anomalies in liver function tests
• Increased liver enzymes

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

• Bleeding may occur in a joint, surgical incision site, wound, injection site, or venous catheter site
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes facial or throat swelling
• Urticaria with dark, prominent, and itchy red bumps, caused by an allergic reaction
• Decreased proportion of blood cells
• Increased liver enzymes
• Yellow discoloration of the skin or white of the eyes, caused by liver or blood problems

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

• Difficulty breathing or wheezing
• Decreased white blood cell count (which helps fight infections)
• Hair loss

In a clinical trial, the index of heart attacks with Dabigatrán etexilato Combix was numerically higher than with warfarin. The global incidence was low.

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/or lungs

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

• Bleeding may occur through the nose, stomach, or intestines, rectum, penis/vagina, or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Indigestion

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

• Bleeding
• Bleeding may occur in a joint or wound
• Bleeding may occur from hemorrhoids
• Decreased red blood cell count in blood
• Formation of hematomas
• Coughing up blood or sputum with blood spots
• Allergic reaction
• Sudden change in skin that affects color and physical appearance
• Itching
• Ulcer in the stomach or intestines (including esophageal ulcer)
• Inflammation of the esophagus and stomach
• Reflex of stomach acid into the esophagus
• Feeling like vomiting
• Vomiting
• Abdominal pain or stomach pain
• Frequent loose or liquid stools
• Anomalies in liver function tests
• Increased liver enzymes

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

• Bleeding may occur in a surgical incision site, injection site, or venous catheter site, or from the brain
• Decreased platelet count in blood
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes facial or throat swelling
• Urticaria with dark, prominent, and itchy red bumps, caused by an allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decreased hemoglobin level in blood (the substance present in red blood cells)
• Decreased proportion of blood cells
• Decreased white blood cell count (which helps fight infections)
• Yellow discoloration of the skin or white of the eyes, caused by liver or blood problems
• Hair loss

In the clinical trial program, the index of heart attacks with Dabigatrán etexilato Combix was higher than with warfarin. The global incidence was low. No imbalance in the index of heart attacks was observed in patients treated with dabigatrán compared to patients treated with placebo.

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

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

• Decreased red blood cell count in blood
• Decreased platelet count in blood
• Urticaria with dark, prominent, and itchy red bumps, caused by an allergic reaction
• Sudden change in skin that affects color and physical appearance
• Formation of hematomas
• Nasal bleeding
• Reflex of stomach acid into the esophagus
• Vomiting
• Feeling like vomiting
• Frequent loose or liquid stools
• Indigestion
• Hair loss
• Increased liver enzymes

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

• Decreased white blood cell count (which helps fight infections)
• Bleeding may occur in the stomach or intestines, brain, rectum, penis/vagina, or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Decreased hemoglobin level in blood (the substance present in red blood cells)
• Decreased proportion of blood cells
• Itching
• Coughing up blood or sputum with blood spots
• Abdominal pain or stomach pain
• Inflammation of the esophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellow discoloration of the skin or white of the eyes, caused by liver or blood problems

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

• Decreased white blood cell count (which helps fight infections)
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes facial or throat swelling
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur in a joint or wound, surgical incision site, injection site, or venous catheter site
• Bleeding may occur from hemorrhoids
• Ulcer in the stomach or intestines (including esophageal ulcer)
• Anomalies in liver function tests

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSpanish System of Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box, blister pack, or bottle after “CAD”. The expiration date is the last day of the month indicated.

Aluminum – Aluminum (or PA/Al/PVC//Al blister): Do not store at a temperature above 30°C.

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

Bottles: Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains or in the trash.Depositthe packaging and medicines that you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. By doing so, you will help protect the environment.

Composition of Dabigatrán etexilate Combix

• The active ingredient is dabigatrán. Each hard capsule contains dabigatrán etexilate mesilate equivalent to 150 mg of dabigatrán etexilate

The other components are:

• Capule content: tartaric acid, hypromellose, hydroxypropylcellulose, talc.
• Capsule coating: indigo carmine, carrageenan, potassium chloride, titanium dioxide, hypromellose.

Appearance of the product and contents of the packaging

Hard capsules of approximately 22.0 mm with a light blue, opaque cap, and a white, opaque body of size “0” filled with off-white to yellowish granules.

The capsules are stored in aluminum blisters with desiccant – aluminum (OPA/Al/PE// PE/Al/LDPE) or aluminum – aluminum (oPA/Al/PVC//Al blister) or a white plastic bottle with silica gel desiccant in the cap (PP).

Packaging sizes:

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

Bottles containing: 100 hard capsules.

Only some packaging sizes may be commercially marketed.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Combix Laboratories, S.L.U.

C/ Badajoz 2, Building 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible manufacturer

Laboratories Liconsa S.A.
Avenida Miralcampo 7
Poligono Industrial Miralcampo
19200, Azuqueca De Henares

Guadalajara

Spain

Last review date of thisleaflet: