Package Insert: Information for the Patient

Dabigatrán etexilate Tevagen110 mg Hard Capsules EFG

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

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you alone, 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 Tevagen contains 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 is used in adults for:

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

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

Dabigatrán etexilato is used in children for:

• treating blood clots and preventing new blood clots from forming.

Do not take Dabigatrán etexilato Tevagen

• 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, head injury or bleeding, recent brain or eye surgery).
• if you are prone to bleeding. This tendency may be congenital, unknown, or caused by other medications.
• if you are taking medications to prevent blood clotting in the blood (e.g., warfarin, rivaroxaban, apixaban, or heparin), except when changing anticoagulant treatment, 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 ketoconazole oral or itraconazole, medications used in the treatment of fungal infections.
• if you are taking oral ciclosporin, a medication used to prevent organ rejection after a transplant.
• if you are taking dronedarone, a medication used to treat abnormal heart rhythm.
• if you are taking a combination product of glecaprevir and pibrentasvir, an antiviral medication used to treat hepatitis C.
• if you have had a heart valve implanted that requires permanent anticoagulant treatment.

Warnings and precautions

Consult your doctor before starting to take dabigatrán etexilato. During treatment with this medication, 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 recent 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 medications that may increase the risk of bleeding. See “Other medications and Dabigatrán etexilato Tevagen” below.
• if you are taking anti-inflammatory medications such as diclofenac, ibuprofen, 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 medication is not recommended in this case.

Be especially careful with Dabigatrán etexilato Tevagen

• if you need to undergo surgery:

In this case, dabigatrán etexilato should be temporarily interrupted due to an increased risk of bleeding during and shortly after surgery. It is very important that you take dabigatrán etexilato exactly at the times indicated 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 exactly at the times indicated by your doctor before and after surgery.
• Inform your doctor immediately if you experience numbness or weakness in your legs or problems with your intestines or bladder 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 a doctor to 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 medications and Dabigatrán etexilato Tevagen

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.Particularly, inform your doctor before takingdabigatrán etexilatoif you are taking any of the following medications:

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

If you are taking medications that contain amiodarone, quinidine, or verapamil, your doctor may instruct you to use a reduced dose of dabigatrán etexilato according to the disease for which you were prescribed it. See also section 3.

• Medications used to prevent organ rejection after a transplant (e.g., tacrolimus, ciclosporin).
• A combination product of glecaprevir and pibrentasvir (an antiviral medication used to treat hepatitis C).
• Anti-inflammatory and pain-relieving medications (e.g., aspirin, ibuprofen, diclofenac).
• St. John's Wort, a medicinal plant for depression.
• Antidepressants called selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors.
• Rifampicin or clarithromycin (two antibiotics).
• Antiviral medications for HIV/AIDS (e.g., ritonavir).
• Certain medications used to treat epilepsy (e.g., carbamazepine, phenytoin).

Pregnancy and breastfeeding

The effects of dabigatrán etexilato on pregnancy and the fetus are unknown. Do not use this medication 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.

Do not breastfeed naturally during treatment with dabigatrán etexilato.

Driving and operating machines

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

Dabigatran etexilate 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 the treatment of children under 8 years old.

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

Take dabigatran etexilate as recommended for the following situations:

Prevention of blood clot formation after knee or hip replacement surgery

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

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

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

If you are taking medications containing verapamil and your renal function is decreased by more than half, you should be instructed to take a reduced dose of 75 mg of dabigatran etexilate, as your risk of bleeding may increase.

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

After knee replacement surgery

Start treatment with dabigatran etexilate 1-4 hours after surgery, taking a single capsule. Then, take 2 capsules once a day for a total of 10 days.

After hip replacement surgery

Start treatment with dabigatran etexilate 1-4 hours after surgery, taking a single capsule. Then, take 2 capsules once a day for a total of 28-35 days.

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

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

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

If you are taking medications containing verapamil, you should be instructed to take a reduced dose of 220 mg taken as a single capsule of 110 mg twice a day, as your risk of bleeding may increase.

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

You can continue taking this medication if necessary to restore your normal heart rhythm by a procedure called cardioversion. Take dabigatran etexilate 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 once your doctor has decided that normal blood coagulation has been achieved. Take dabigatran etexilate as instructed by your doctor.

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

Dabigatran etexilate 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. Follow all other medications unless your doctor tells you to stop taking one.

Table 1 shows the single doses and total daily doses of dabigatran etexilate 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

Single doses that require combinations of more than one capsule:

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

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

220 mg: two capsules of 110 mg

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

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

How to take Dabigatran etexilate Tevagen

Dabigatran etexilate 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 blisters

The following images illustrate how to extract the dabigatran etexilate capsules from the blister:

Separate an individual blister from the blister strip through the perforated line.

Remove the rear sheet and extract the capsule

• Do not press the capsules through the blister sheet.
• Do not remove the blister sheet until the capsule is needed.

Change in anticoagulant treatment

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

If you take more Dabigatran etexilate Tevagen 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 Tevagen

Prevention of blood clot formation after knee or hip replacement surgery

Take the remaining daily doses of dabigatran etexilate at the same time the next day.

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

Use in adults: Prevention of cerebral or systemic vascular obstruction by blood clot formation developed after abnormal heart rhythm 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 recurrence of 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 Tevagen

Take dabigatran etexilate 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.

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 etexilate acts on blood coagulation; therefore, most side effects are related to signs such as bruising or bleeding.

Bleeding episodes, major or severe, are the most serious side effects and, regardless of their location, can cause disability, be potentially fatal, or even cause death. In some cases, these bleeding episodes may not be evident.

If you experience any bleeding episode that does not stop on its own 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 side effects are listed below, grouped by frequency of occurrence.

Prevention of blood clot formation after knee or hip arthroplasty

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

• Decreased blood hemoglobin levels (the substance present in red blood cells)
• Anomalies in liver function tests

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

• Bleeding may occur from the nose, stomach, or intestines, penis/vagina, or urinary tract (including blood in the urine that turns the urine pink or red), hemorrhoids, rectum, under the skin, from a joint, from a wound, or after surgery
• Formation of hematomas or bruising after surgery
• Blood detected in stool in a laboratory test
• Decreased red blood cell count in the blood
• Decreased proportion of blood cells
• Allergic reaction
• Vomiting
• Frequent loose or liquid stools
• Discomfort
• Wound supuration (secretion of liquid from a surgical wound)
• Increased liver enzymes
• Yellow discoloration of the skin or white of the eyes, caused by liver or blood problems

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 site of an injection, or at the site of a venous catheter
• Suppurative venous catheter site
• Coughing up blood or sputum with blood spots
• Decreased platelet count in the blood
• Decreased red blood cell count in the blood after surgery
• 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
• Change in skin color and appearance
• Itching
• Ulcer in the stomach or intestines (including esophageal ulcer)
• Esophageal and stomach inflammation
• Gastroesophageal reflux
• Abdominal pain or stomach pain
• Indigestion
• Dysphagia
• Liquid leaking from a wound
• Liquid leaking from a wound after surgery

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

• Difficulty breathing or wheezing
• Decreased or absence of leukocytes (which help fight infections)
• Hair loss

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

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

• Bleeding may occur from 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
• Discomfort

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 the blood
• Decreased hemoglobin levels in the blood (the substance present in red blood cells)
• Allergic reaction
• Change in skin color and appearance
• Itching
• Ulcer in the stomach or intestines (including esophageal ulcer)
• Esophageal and stomach inflammation
• Gastroesophageal reflux
• Vomiting
• Dysphagia
• Anomalies in liver function tests
• Increased liver enzymes

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 venous catheter or from the brain
• Decreased platelet count in the 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
• Dysphagia

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

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

In a clinical trial, the index of heart attacks with dabigatrán etexilate 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 from 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 in a wound
• Bleeding may occur from hemorrhoids
• Decreased red blood cell count in the blood
• Formation of hematomas
• Coughing up blood or sputum with blood spots
• Allergic reaction
• Change in skin color and appearance
• Itching
• Ulcer in the stomach or intestines (including esophageal ulcer)
• Esophageal and stomach inflammation
• Gastroesophageal reflux
• Discomfort
• Vomiting
• Abdominal pain or stomach pain
• Frequent loose or liquid stools

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

• Bleeding may occur at the site of a surgical incision, at the site of an injection, at the site of a venous catheter, or from the brain
• Decreased platelet count in the 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
• Dysphagia

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

• Difficulty breathing or wheezing
• Decreased hemoglobin levels in the blood (the substance present in red blood cells)
• Decreased proportion of blood cells
• Decreased or absence of leukocytes (which help 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 etexilate was higher than with warfarin. The overall 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 the blood
• Decreased platelet count in the blood
• Urticaria with dark, prominent, and itchy red bumps, caused by an allergic reaction
• Change in skin color and appearance
• Formation of hematomas
• Nasal bleeding
• Gastroesophageal reflux
• Vomiting
• Discomfort
• Frequent loose or liquid stools
• Indigestion
• Hair loss
• Increased liver enzymes

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

• Decreased leukocyte count (which help fight infections)
• Bleeding may occur from 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 levels in the 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
• Esophageal and stomach inflammation
• Allergic reaction
• Dysphagia
• 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 leukocyte count (which help 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 in a wound, in a surgical incision, at the site of an injection, or at the site of a venous catheter
• 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 the Spanish System for 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.

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

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

Do not store above 30°C

Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains or in the trash.Deposit the packaging and medicines that you no longer need at the SIGRE collection point at the pharmacy.Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

Composition of Dabigatrán etexilato Tevagen

• The active ingredient is dabigatrán. Each hard capsule contains 126.83 mg of dabigatrán etexilato (in the form of mesilato) equivalent to 110 mg of dabigatrán etexilato.
• The other components are tartaric acid, gum arabic, hypromellose 2910, dimethicone 350, talc and hydroxypropylcellulose.
• The capsule coating contains carrageenan, potassium chloride, titanium dioxide (E-171), hypromellose 2910, and indigo carmine (E-132).

Appearance of the product and contents of the package

Dabigatrán etexilato Tevagen 110 mg are hard blue capsules, size 1, filled with pale yellowish to white granules.

This medication is available in packages containing:

Aluminum/OPA-AL-PVC blister packs of 10 x 1, 30 x 1, or 60 x 1 hard capsules.

Multi-pack containing 4 packages of 50 x 1 hard capsules (200 hard capsules), multi-pack containing 3 packages of 60 x 1 hard capsules (180 hard capsules), or multi-pack containing 2 packages of 50 x 1 hard capsules (100 hard capsules) with aluminum/OPA-AL-PVC blister packs.

Only some package sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

Teva Pharma, S.L.U.

C/ Anabel Segura, 11 - Edificio Albatros B, 1st floor.

28108, Alcobendas (Madrid)

Spain

Responsible manufacturer:

Galenicum Health, S.L.U.

Avda. Cornella, 144

08950 – Esplugues de Llobregat (Barcelona)

Spain

or

SAG Manufacturing S.L.U

Crta. N-I, Km 36

28750 San Agustin de Guadalix,

Madrid,

Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Spain:Dabigatrán etexilato Tevagen 110 mg hard capsules EFG

Malta:Dabigatran etexilate SAG 110 hard capsules

Last review date of this leaflet:December 2023

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