PRADAXA 75 mg HARD CAPSULES

2. What you need to know before you take Pradaxa

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 bleeding.
• if you have a 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 inborn, of unknown cause or caused by other medicines.
• if you are taking medicines to prevent blood clot formation (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 given heparin through this catheter to keep it open or while your normal heart rhythm is being restored by a procedure called catheter ablation for atrial fibrillation.
• if your liver function is severely reduced or you have a life-threatening liver disease.
• if you are taking oral ketoconazole or itraconazole, medicines used to treat fungal infections.
• if you are taking oral ciclosporin, a medicine used to prevent organ rejection after a transplant.
• if you are taking dronedarone, a medicine used to treat irregular heart rhythm.
• if you are taking a combination product of glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C.
• if you have been implanted with an artificial heart valve that requires permanent anticoagulant treatment.

Warnings and precautions

Talk to your doctor before you start taking Pradaxa. During treatment with this medicine, you may also need to talk to your doctor if you experience any symptoms or if you need to have 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 surgical removal of tissue (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 stomach acid flowing back into the oesophagus.

• if you are taking medicines that may increase the risk of bleeding. See “Other medicines and Pradaxa” below.
• if you are using anti-inflammatory medicines 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-coloured 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 an infection in the brain or around the brain.

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

Be careful with Pradaxa

• If you need to have surgery:

In this case, Pradaxa must be temporarily stopped due to an increased risk of bleeding during and after surgery. It is very important that you take Pradaxa before and after surgery exactly at the times your doctor has told you.

• If surgery requires the insertion of a catheter or injection into the spinal column (e.g. for epidural or spinal anaesthesia or for pain relief):

• It is very important that you take Pradaxa before and after surgery exactly at the times your doctor has told you.
• Tell your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after the anaesthesia has ended, 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 an increased 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 so that they can decide whether your treatment needs to be changed.

Other medicines and Pradaxa

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. In particular, you must tell 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, aspirin)
• Medicines for treating fungal infections (e.g. ketoconazole, itraconazole), except if they are only applied to the skin
• Medicines used to treat irregular heart rhythm (e.g. amiodarone, dronedarone, quinidine, verapamil)

If you are using medicines that contain amiodarone, quinidine or verapamil, your doctor may tell you to use a reduced dose of Pradaxa depending on the disease for which you have been prescribed. See also section 3.

• Medicines for preventing organ rejection after a transplant (e.g. tacrolimus, ciclosporin)
• A combination product of glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C)
• Anti-inflammatory and pain-relieving medicines (e.g. aspirin, ibuprofen, diclofenac)
• St John’s Wort, a herbal medicine for depression
• Antidepressant medicines called selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors
• Rifampicin or clarithromycin (two antibiotics)
• Antiviral medicines for HIV (e.g. ritonavir)
• Certain medicines for treating epilepsy (e.g. carbamazepine, phenytoin)

Pregnancy and breast-feeding

The effects of Pradaxa on pregnancy and the unborn child are not known. You should 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, you should avoid becoming pregnant during treatment with Pradaxa.

Breast-feeding is not recommended during treatment with Pradaxa.

Driving and using machines

Pradaxa has no known effects on the ability to drive or use machines.

3. How to take Pradaxa

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

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, ask your doctor again.

Take Pradaxa as recommended for the following situations:

Prevention of blood clot formation after knee or hip replacement surgery

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

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

If you are using medicines that contain amiodarone, quinidine or verapamilthe recommended dose is 150mg once a day(given as 2 capsules of 75 mg).

If you are using medicines that contain verapamil and your kidney function is reducedby more than half, you should be given a reduced dose of Pradaxa of 75mgbecause your risk of bleeding may be increased.

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

After knee replacement surgery

Treatment with Pradaxa should be started 1-4 hours after the operation, taking a single capsule. After this, 2 capsules should be taken once a day for a total of 10 days.

After hip replacement surgery

Treatment with Pradaxa should be started 1-4 hours after the operation, taking a single capsule. After this, 2 capsules should be taken once a day for a total of 28-35 days.

Treatment of blood clots and prevention of blood clots forming again 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 dosing 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 your other medicines unless your doctor tells you to stop using any.

Table 1 shows the single 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: Dosing table for Pradaxa capsules

Doses that require combinations of more than one capsule:

300 mg: 2 capsules of 150 mg or 4 capsules of 75 mg

260 mg: 1 capsule of 110 mg plus 1 capsule of 150 mg or 1 capsule of 110 mg plus 2 capsules of 75 mg

220 mg: 2 capsules of 110 mg

185 mg: 1 capsule of 75 mg plus 1 capsule of 110 mg

150 mg: 1 capsule of 150 mg or 2 capsules of 75 mg

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 remove the Pradaxa capsules from the blister:

Separate a single blister from the blister strip through the perforated line.

Remove the back layer and take out the capsule.

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

Instructions for the bottle

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

Changing 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 medicine increases the risk of bleeding. Contact your doctor immediately if you have taken too many capsules. Specific treatment options are available.

If you forget to take Pradaxa

Prevention of blood clot formation after 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 make up for forgotten doses.

Treatment of blood clots and prevention of blood clots forming again in children

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

A forgotten dose should be omitted if the time before the next dose is less than 6 hours.

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

If you stop taking Pradaxa

Take Pradaxa exactly as prescribed. Do not stop your treatment with this medicine without first talking to your doctor, as the risk of developing a blood clot may be greater if you stop treatment too soon. Contact your doctor if you experience indigestion after taking Pradaxa.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Pradaxa 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, regardless of their location, can cause disability, be potentially life-threatening, or even cause death. 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.

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

Prevention of blood clot formation after knee or hip replacement surgery

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

• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Anomalies in liver function tests

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

• Bleeding may occur from the nose, stomach, or intestine, from the penis/vagina or urinary tract (including blood in the urine that stains the urine pink or red), from hemorrhoids, rectum, under the skin, from a joint, or after an injury or surgery
• Formation of hematomas or bruising after surgery
• Detection of blood in stool in a laboratory test
• Decrease in the number of red blood cells in the blood
• Decrease in the proportion of blood cells
• Allergic reaction
• Vomiting
• Frequent loose or liquid stools
• Feeling of nausea
• Pus discharge from a surgical wound
• Increased liver enzymes
• Yellowish discoloration of the skin or whites 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 catheter in a vein
• Bloody pus discharge from the site of a catheter in a vein
• Coughing up blood or sputum with blood spots
• Decrease in the number of platelets in the blood
• Decrease in the number of red blood cells in the blood after surgery
• Severe allergic reaction 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
• 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
• Reflux of gastric juice into the esophagus
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Fluid leaking from a wound
• Fluid leaking from a wound after surgery

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

• Difficulty breathing or wheezing
• Decrease in the number or even absence of white blood cells (which help fight infections)
• Hair loss

Treatment of blood clots and prevention of blood clot formation 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
• Nosebleeds
• Reflux of gastric juice into the esophagus
• Vomiting
• Feeling of nausea
• Frequent loose or liquid stools
• Indigestion
• Hair loss
• Increased liver enzymes

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

• Decrease in the number of white blood cells (which help fight infections)
• Bleeding may occur in the stomach or intestine, brain, rectum, 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 whites of the eyes, caused by liver or blood problems

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

• Absence of white blood cells (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 wound, at the site of 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 intestine (including ulcer in the esophagus)
• Anomalies in liver function tests

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Pradaxa

Keep this medicine out of the 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.

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

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Pradaxa

• The active ingredient is dabigatran. Each hard capsule contains 75 mg of dabigatran etexilate (as mesilate).

• The other ingredients are tartaric acid, arabic gum, hypromellose, dimeticone 350, talc, and hydroxypropylcellulose.

• The capsule shell contains carrageenan, potassium chloride, titanium dioxide, and hypromellose.

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

Appearance and Package Contents

Pradaxa 75 mg are hard capsules (approx. 18 × 6 mm) with a white opaque cap and a white opaque body. The Boehringer Ingelheim logo is printed on the cap and the code "R75" on the body of the hard capsule.

This medicine is available in packs containing 10 × 1, 30 × 1, or 60 × 1 hard capsules in perforated aluminum unit-dose blisters. Pradaxa is also 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.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

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

You can request more information about this medicine from the local representative of the marketing authorization holder:

Date of Last Approval of this Leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.