DABIGATRAN ETEXILATE COMBIX 150 mg HARD CAPSULES

Introduction

Package Leaflet:information for the patient

Dabigatran etexilate Combix150 mg hard capsules EFG

dabigatran etexilate

Read the entire package leaflet carefully before starting to take this medication,as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medication has been prescribed to you only, 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 side effects, consult your doctor or pharmacist, even if they are side effects not listed in this package leaflet. See section 4.

Contents of the package leaflet

1. What is Dabigatran etexilate Combix and what is it used for
2. What you need to know before taking Dabigatran etexilate Combix
3. How to take Dabigatran etexilate Combix
4. Possible side effects
5. Storage of Dabigatran etexilate Combix
6. Package contents and additional information

1. What is Dabigatran etexilate Combix and what is it used for

Dabigatran etexilate Combix contains the active substance dabigatran etexilate and belongs to a group of medications called anticoagulants. It works by blocking a substance in the body involved in the formation of blood clots.

Dabigatran etexilate Combix is used in adults to:

• prevent the formation of blood clots in the brain (stroke) and in other blood vessels of 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 them from forming again in the veins of your legs and lungs.

Dabigatran etexilate Combix is used in children to:

• treat blood clots and prevent them from forming again.

2. What you need to know before taking Dabigatran etexilate Combix

Do not take Dabigatran etexilate Combix

• if you are allergic to dabigatran etexilate or any of the other ingredients of this medication (listed in section 6).
• if your kidney function is severely reduced.
• if you are currently 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 brain or eye surgery).
• if you are prone to bleeding. This tendency may be congenital, of unknown cause, or caused by other medications.
• if you are taking medications to prevent blood clotting (e.g., warfarin, rivaroxaban, apixaban, or heparin), except when switching from one anticoagulant treatment to another, while having a venous or arterial catheter and being administered heparin through this catheter to keep it open, or while your normal heartbeat is being restored through a procedure called catheter ablation for atrial fibrillation.
• if your liver function is severely impaired or you have a life-threatening liver disease.
• if you are taking oral ketoconazole or itraconazole, medications used to treat fungal infections.
• if you are taking oral cyclosporine, a medication used to prevent organ rejection after a transplant.
• if you are taking dronedarone, a medication used to treat abnormal heartbeat.
• if you are taking a combination product of glecaprevir and pibrentasvir, an antiviral medication 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 Dabigatran etexilate Combix. During treatment with this medication, you may also need to consult your doctor if you experience any symptoms or if you need to undergo surgery.

Tell 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 removal (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 gastric juice reflux in the esophagus.
  • if you are taking medications that may increase the risk of bleeding. See "Other medications and Dabigatran etexilate Combix" below.
  • if you are using anti-inflammatory medications such as diclofenac, ibuprofen, or piroxicam.
  • if you have a heart infection (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-colored urine).
  • if you are over 75 years old.
  • if you are an adult patient and weigh 50 kg or less.
  • only if used in children: if the child has a brain infection or around the brain.

• If you have had a heart attack or have been diagnosed with diseases 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 medication is not recommended in this case.

Be careful with Dabigatran etexilate Combix

• If you need to undergo surgery:

In this case, Dabigatran etexilate Combix should be temporarily discontinued due to an increased risk of bleeding during and after surgery. It is very important that you take Dabigatran etexilate Combix before and after surgery exactly at the times indicated by your doctor.

• If surgery 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 Dabigatran etexilate Combix before and after surgery exactly at the times indicated by your doctor.
  • Tell your doctor immediately if you experience numbness or weakness in your legs or intestinal or bladder problems after the end of anesthesia, as this situation requires urgent attention.
• If you fall or injure yourself during treatment, especially if you hit your head. Seek urgent medical attention. You may need a doctor to examine you, as you may have a higher risk of bleeding.

• If you know you have a disease called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), tell your doctor to decide if it may be necessary to modify the treatment.

Other medications and Dabigatran etexilate Combix

Tell your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication. In particular, you must tell your doctor before taking Dabigatran etexilate Combix if you are taking any of the following medications:

• Medications to reduce blood clotting (e.g., warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid)
• Medications for the treatment of fungal infections (e.g., ketoconazole, itraconazole), except if only applied to the skin
• Medications used in the treatment of abnormal heartbeat (e.g., amiodarone, dronedarone, quinidine, verapamil)

If you are using medications that contain amiodarone, quinidine, or verapamil, your doctor may indicate that you use a reduced dose of Dabigatran etexilate Combix according to the disease for which it was prescribed. See also section 3.

• Medications for the prevention of organ rejection after a transplant (e.g., tacrolimus, cyclosporine)
• A combination product of glecaprevir and pibrentasvir (an antiviral medication used to treat hepatitis C)
• Anti-inflammatory and pain-relieving medications (e.g., acetylsalicylic acid, ibuprofen, diclofenac)
• St. John's Wort, a herbal remedy for depression
• Antidepressant medications called selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors
• Rifampicin or clarithromycin (two antibiotics)
• Antiviral medications for HIV (e.g., ritonavir)
• Certain medications for the treatment of epilepsy (e.g., carbamazepine, phenytoin)

Pregnancy and breastfeeding

The effects of Dabigatran etexilate Combix on pregnancy and the fetus are unknown. You should not use this medication if you are pregnant unless your doctor indicates that it is safe to do so. If you are of childbearing age, you should avoid becoming pregnant during treatment with Dabigatran etexilate Combix.

Breastfeeding is not recommended during treatment with Dabigatran etexilate Combix.

Driving and using machines

Dabigatran etexilate Combix has no known effects on the ability to drive and use machines.

3. 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. There are other pharmaceutical forms suitable for the treatment of children under 8 years of age.

Follow your doctor's instructions for taking this medication exactly. If you are in doubt, consult your doctor again.

Take Dabigatran etexilate Combix as recommended for the following situations:

Prevention of cerebral or systemic vascular obstruction by blood clot formation after abnormal heartbeat and treatment of blood clots in the veins of your legs and lungs, including prevention of blood clots in the veins of your legs and lungs

The recommended dose is 300 mg administered as one 150 mg capsule twice a day.

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

If you are using medications that contain verapamil, you should be indicated a reduced dose of Dabigatran etexilate Combix of 220 mg taken as one 110 mg capsule twice a day, as your risk of bleeding may be increased.

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

You can continue taking this medication if you need to restore your normal heartbeat through a procedure called cardioversion. Take Dabigatran etexilate Combix as your doctor has indicated.

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

Treatment of blood clots and prevention of blood clots 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 indicates that you should stop using one.

Table 1 shows the single 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:Dabigatran etexilate Combix capsule dosing table

Doses that require 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.

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 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 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 same time the next day.

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

Adult use: Prevention of cerebral or systemic vascular obstruction by blood clot formation after abnormal heartbeat and treatment of blood clots in the veins of your legs and lungs, including prevention of blood clots in the veins of your legs and lungs

Child use: Treatment of blood clots and prevention of blood clots

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

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

If you stop treatment with Dabigatran etexilate Combix

Take Dabigatran etexilate Combix exactly as prescribed. Do not stop your treatment with this medication without consulting your doctor first, as the risk of developing a blood clot may be higher if you stop 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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from 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 are the most serious adverse effects and can cause disability, be potentially life-threatening, or even cause death, regardless of their location. In some cases, these bleedings may not be apparent.

If you experience any episode of bleeding that does not stop by itself or if you experience signs of excessive bleeding (exceptional 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 that causes difficulty breathing or dizziness.

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

Prevention of vascular cerebral or systemic 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, in the stomach or intestine, from the penis/vagina or urinary tract (including blood in the urine that stains the 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 liquid stools
• Feeling like vomiting

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

• Bleeding
• Bleeding may occur from hemorrhoids, the rectum, or the brain
• Formation of hematomas
• 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 skin color and physical appearance
• Itching
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflex of gastric juice into the esophagus
• Vomiting
• Difficulty swallowing
• Anomalies in liver function tests

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

• Bleeding may occur in a joint, at the site of a surgical incision, in a wound, at the site of an injection, or at the site of a catheter entry in a vein
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Skin rash with dark red, prominent, and itchy bumps, caused by an allergic reaction
• Decrease in the proportion of blood cells
• Increase in liver enzymes
• Yellowish discoloration of the skin or the whites of the eyes, caused by liver or blood problems

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 veins of the legs and/or lungs

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

• Bleeding may occur through the nose, in the stomach or intestine, from the rectum, from the penis/vagina or urinary tract (including blood in the urine that stains the 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 in a wound
• Bleeding may occur from hemorrhoids
• Decrease in the number of red blood cells in the blood
• Formation of hematomas
• Coughing up blood or sputum with blood spots
• Allergic reaction
• Sudden change in skin color and physical appearance
• Itching
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflex of gastric juice into the esophagus
• Feeling like vomiting
• Vomiting
• Abdominal pain or stomach pain
• Frequent loose or liquid stools
• Anomalies in liver function tests
• Increase in liver enzymes

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

• Bleeding may occur at the site of a surgical incision, or at the site of an injection, or at the site of a catheter entry in a vein or from the brain
• Decrease in the number of platelets in the blood
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Skin rash with dark red, prominent, and 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)
• Yellowish discoloration of the skin or the whites of the eyes, caused by liver or blood problems
• 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 of blood clots 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, prominent, and itchy bumps, caused by an allergic reaction
• Sudden change in skin color and physical appearance
• Formation of hematomas
• Nasal bleeding
• Reflex of gastric juice into the esophagus
• Vomiting
• Feeling like vomiting
• Frequent loose or liquid stools
• Indigestion
• Hair loss
• Increase in 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, from the brain, from the rectum, from the penis/vagina or urinary tract (including blood in the urine that stains the 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 pain
• Inflammation of the esophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowish discoloration of the skin or the whites of the eyes, caused by liver or blood problems

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

• Absence of leukocytes (which help fight infections)
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur in a joint or in a wound, in a surgical incision, at the site of an injection, or at the site of a catheter entry in a vein
• Bleeding may occur from hemorrhoids
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Anomalies 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 that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Dabigatran etexilate Combix

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date stated on the carton, blister, or bottle after "EXP". The expiration 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 cover – Aluminum (OPA/Al/PE// PE/Al/LDPE): No special storage conditions required.

Bottles: Store in the original package to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Dabigatran etexilate Combix

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

The other components are:

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

Appearance of the Product and Package Contents

Hard capsules approximately 22.0 mm in size with a light blue, opaque cap and a white, opaque body of size "0" filled with white to yellowish granules.

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

Package sizes:

Blister packages 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.

Not all package sizes may be marketed.

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 7Poligono Industrial Miralcampo19200, Azuqueca De Henares

Guadalajara

Spain

Date of the Last Revision of this Prospectus: