Package Insert: Information for the Patient

Pradaxa 110 mg Hard Capsules

dabigatrán etexilato

Read this package insert carefully before you start taking this medicine, 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 medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Pradaxa contains the active ingredient dabigatrán etexilato and belongs to a group of medications known as anticoagulants. It works by blocking a substance in the body involved in the formation of blood clots.

Pradaxa is used in adults for:

• preventing the formation of blood clots in veinsafter a knee or hip arthroplasty.

• 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.

Pradaxa is used in children for:

• treating blood clots and preventing them from reforming.

Do not take Pradaxa

• if you are allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6).
• if your kidney function is severely reduced.
• if you are currently experiencing bleeding.
• if you have 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 may be due to birth, unknown cause, or caused by other medicines.
• if you are taking medicines to prevent blood clotting in the blood (e.g. warfarin, rivaroxaban, apixaban or heparin), except when changing from one anticoagulant treatment to another, 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 if you have any liver disease that may be fatal.
• if you are taking ketoconazole oral or itraconazole, medicines used in the treatment of fungal infections.
• if you are taking ciclosporin oral, a medicine used to prevent organ rejection after a transplant.
• 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 permanent anticoagulant treatment.

Warnings and precautions

Consult your doctor before starting to take Pradaxa. 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 experienced 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 oesophagus or stomach.
• if you have problems with reflux of stomach acid into the oesophagus.
• if you are taking medicines that may increase the risk of bleeding. See“Other medicines and Pradaxa”below.
• if you are taking anti-inflammatory medicines such as diclofenac, ibuprofen or piroxicam.
• if you have a bacterial infection of the heart (bacterial endocarditis).
• if you know that your kidneys are not functioning properly or if you are dehydrated (symptoms include feeling thirsty and passing small amounts of dark, concentrated urine with foam).
• if you are over 75 years old.
• ifyou are an adult andyou weigh50kgor less.
• onlyif 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 Pradaxa

• if you are to undergo surgery:

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

• if surgery requires the placement of a catheter or injection into the spine (e.g. for epidural or spinal anaesthesia or for pain relief):

• It is very important that you take Pradaxa exactly as instructed 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 anaesthesia, as this 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 medicines and Pradaxa

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine.Particularly, you must inform your doctor before takingPradaxa 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 used in the treatment of fungal infections (e.g. ketoconazole, itraconazole), except when applied to the skin.
• Medicines used in the treatment of abnormal heart rhythm (e.g. amiodarone, dronedarone, quinidine, verapamil).
• if you are using medicines that contain amiodarone, quinidine or verapamil, your doctor may instruct you to use a reduced dose of Pradaxa according to the disease for which you have been prescribed it. See section3.
• Medicines used to prevent organ rejection after a transplant (e.g. tacrolimus, ciclosporin).
• A combination product ofglecaprevir 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 medicinal herb for depression.
• Antidepressants called selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors.
• Rifampicin or clarithromycin (two antibiotics).
• Antiviral medicines for HIV/AIDS (e.g. ritonavir).
• Certain medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding

The effects of Pradaxa 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 Pradaxa.

Pradaxa is not recommended during breastfeeding.

Driving and operating machines

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

Pradaxa capsules can be used in adults and children aged 8 years or older who are able to swallow the capsules whole. Pradaxa granulated coating is available for the treatment of children under 12 years old when they are able to swallow soft foods.

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

Take Pradaxa as recommended for the following situations:

Prevention of blood clot formation after a knee or hip replacement surgery

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

If your kidney 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 in the form of 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 in the form of 2 capsules of 75 mg).

If you are taking medications containing verapamil and your kidney function is decreased by more than half, you should be instructed to take a reduced dose of Pradaxa of 75 mg due to an increased risk of bleeding.

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 a knee replacement surgery

You should start treatment with Pradaxa 1-4 hours after surgery, taking a single capsule. You should then take 2 capsules once a day for a total of 10 days.

After a hip replacement surgery

You should start treatment with Pradaxa 1-4 hours after surgery, taking a single capsule. You should then take 2 capsules once a day for a total of 28-35 days.

Prevention of cerebral or systemic vascular obstruction due to 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 in the form of one capsule of 150 mg twice a day.

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

If you are taking medications containing verapamil, you should be instructed to take a reduced dose of Pradaxa of 220 mg taken in the form of one 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 in the form of one capsule of 110 mg twice a day.

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

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

Pradaxa 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 using one.

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

Table 1: Pradaxa capsules dosage table

Single doses that require combinations of more than one capsule:

How to take Pradaxa

Pradaxa 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 Pradaxa capsules from the blister:

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

Instructions for the bottle

• Press and turn to open.
• After removing the capsule, put the closure capsule back in the bottle and close the bottle immediately after taking your dose.

Change of anticoagulant treatment

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

If you take more Pradaxa 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.

If you forget to take Pradaxa

Prevention of blood clot formation after a knee or hip replacement surgery

Take the remaining daily doses of Pradaxa 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 due to 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 Pradaxa

Take Pradaxa 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 Pradaxa.

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.

Pradaxa acts on blood coagulation; therefore, most side effects are related to signs such as bruising or bleeding.Severe or major bleeding episodes, which are the most serious side effects, may occur, regardless of their location, and may 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, 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 blood clot formation after knee or hip replacement surgery

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

Poorly frequent (may affect up to 1 in 100 people):

• Bleeding may occur from the nose, stomach, or intestines, from the penis/vagina or urinary tract (including blood in the urine that turns the urine pink or red), from hemorrhoids, from the 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
• Decreased proportion of blood cells
• Allergic reaction
• Vomiting
• Frequent loose or liquid stools
• Feeling like vomiting
• Suppuration of wounds (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 10,000 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 catheter in a vein
• Suppurative bleeding from the site of a catheter in a vein
• Coughing up blood or sputum with blood spots
• Decreased platelet count in blood
• Decreased red blood cell count 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 ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflux of stomach juice into the esophagus
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• 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 white blood cell count (which helps 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, from the 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
• Abdominal pain or stomach pain
• Indigestion
• Frequent loose or liquid stools
• Feeling like vomiting

Poorly frequent (may affect up to 1 in 100 people):

• Bleeding
• Bleeding may occur from hemorrhoids, from the rectum, or in the brain
• Formation of hematomas
• Coughing up blood or sputum with blood spots
• Decreased platelet count in blood
• Decreased blood hemoglobin levels (the substance present in red blood cells)
• Allergic reaction
• Change in skin color and appearance
• Itching
• Ulcer in the stomach or intestines (including ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflux of stomach juice into the esophagus
• Vomiting
• Difficulty swallowing
• Anomalies in liver function tests

Rare (may affect up to 1 in 10,000 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 in a vein
• 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 incidence of heart attacks with Pradaxa was numerically higher than with warfarin. The overall 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 from the nose, stomach, or intestines, from the rectum, from the penis/vagina or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Indigestion

Poorly frequent (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
• 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 ulcer in the esophagus)
• Inflammation of the esophagus and stomach
• Reflux of stomach juice into the esophagus
• Vomiting
• Dolor en el abdomen o dolor de estómago
• Deposiciones sueltas o líquidas frecuentes
• Anomalías en las pruebas de función hepática
• Aumento de enzimas hepáticas

Rare (may affect up to 1 in 10,000 people):

• Bleeding may occur at the site of a surgical incision, at the site of an injection, at the site of a catheter in a vein, 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 blood hemoglobin levels (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
• Caída del cabello

In the clinical trial program, the incidence of heart attacks with Pradaxa was higher than with warfarin. The overall incidence was low. No imbalance in the incidence 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):

• Decreased red blood cell count
• Decreased platelet count in 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
• Reflux of stomach juice into the esophagus
• Vomiting
• Feeling like vomiting
• Frequent loose or liquid stools
• Indigestion
• Caída del cabello
• Aumento de enzimas hepáticas

Poorly frequent (may affect up to 1 in 100 people):

• Decreased white blood cell count (which helps fight infections)
• Bleeding may occur from the stomach or intestines, from the brain, from the rectum, from the penis/vagina or urinary tract (including blood in the urine that turns the urine pink or red), or under the skin
• Decreased blood hemoglobin levels (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 in a wound, in a surgical incision, at the site of an injection, or at the site of a catheter in a vein
• Bleeding may occur from hemorrhoids
• Ulcer in the stomach or intestines (including ulcer in the esophagus)
• Anomalías en las pruebas de función hepática

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 leaflet.You can also report them directlythrough theAppendixV. 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 box, blister pack, or bottle after “CAD”. The expiration date is the last day of the month indicated.

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

Bottle:Once opened, the medication must be used within 4 months. Keep the bottle perfectly closed. Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Pradaxa

• The active ingredient is dabigatran. Each hard capsule contains 110 mg of dabigatran etexilate (in the form of mesilate).

• The other components are tartric acid, arabic gum, hypromellose, dimethicone 350, talc, and hydroxypropylcellulose.

• The capsule coating contains carrageenan, potassium chloride, titanium dioxide, indigo carmine, and hypromellose.

• The black ink contains shellac, iron oxide black, and potassium hydroxide.

Appearance of the product and contents of the pack

Pradaxa 110 mg are hard capsules (approx. 19 × 7 mm) with an opaque blue-gray cap and an opaque blue-gray body. The Boehringer Ingelheim logo is printed on the cap, and the code “R110”, on the hard capsule body.

This medicine is available in packs containing 10 × 1, 30 × 1, or 60 × 1 hard capsules, a multiple pack containing 3 packs of 60 × 1 hard capsules (180 hard capsules), or a multiple pack containing 2 packs of 50 × 1 hard capsules (100 hard capsules) in perforated aluminum unit dose blisters. Additionally, Pradaxa is available in packs containing 60 × 1 hard capsules in white perforated aluminum unit dose blisters.

This medicine is also available in polypropylene (plastic) bottles with 60 hard capsules.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Responsible for manufacturing

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

and

Boehringer Ingelheim France

100-104 avenue de France

75013 Paris

France

For further information about this medicinal product, please consult the representative of the marketing authorization holder in your country:

Last approval date of this leaflet:

The detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu /.