PRADAXA 150 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 heartbeat is being restored through 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 heartbeat.
• 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

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.

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 tissue sample taken (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 acid reflux from the stomach 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/concentrated urine with foam).
• 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 are to undergo surgery:

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

• If surgery requires the insertion of a catheter or an 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 indicated by your doctor.
• 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 to be examined by a doctor, 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 it may be necessary to change your treatment.

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, acetylsalicylic acid)
• Medicines for the treatment of fungal infections (e.g. ketoconazole, itraconazole), unless they are only applied to the skin
• Medicines used to treat irregular heartbeat (e.g. amiodarone, dronedarone, quinidine, verapamil)

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

• Medicines for the prevention of 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. acetylsalicylic acid, 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 the treatment of epilepsy (e.g. carbamazepine, phenytoin)

Pregnancy and breast-feeding

The effects of Pradaxa on pregnancy and the fetus are not known. You should not use this medicine if you are pregnant unless your doctor advises you to. If you are of childbearing potential, 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 of age 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, consult your doctor again.

Take Pradaxa as recommended for the following situations:

Prevention of stroke or systemic embolism 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 given as one150mg capsule twice daily.

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

If you are using medicines that contain verapamil, you should be instructed to use a reduced dose of Pradaxa of 220 mg given as one 110mg capsule twice daily, 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 given as one 110mg capsule twice daily.

You can continue to take this medicine if you need to have your normal heartbeat restored through a procedure called cardioversion or through a procedure called catheter ablation for atrial fibrillation. Take Pradaxa as instructed by your doctor.

If you have been implanted with a medical device (vascular endoprosthesis) in a blood vessel to keep it open in a procedure called percutaneous coronary intervention with vascular endoprosthesis, you may receive treatment with Pradaxa once your doctor has decided that normal blood clotting control 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 daily, 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 to use all 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.

Doses that require combinations of more than one capsule:

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

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

220 mg: two 110 mg capsules

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

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

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 blister packs

The following images illustrate how to remove the Pradaxa capsules from the blister pack:

Separate one individual blister pack from the strip of blister packs through the perforated line.

Remove the rear foil and take out the capsule.

• Do not press the capsules through the blister pack foil.
• Do not remove the blister pack foil 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 tightly immediately after taking your dose.

Switching from one anticoagulant treatment to another

Do not switch from one anticoagulant treatment to another 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

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

A missed 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 missed doses.

If you stop taking Pradaxa

Take Pradaxa exactly as prescribed. Do not stop your treatment with this medicine 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 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 detailed below, grouped according to their frequency of occurrence.

Prevention of cerebral or systemic vascular obstruction due to 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 intestine, 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, rectum, or 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 esophageal ulcer)
• Inflammation of the esophagus and stomach
• Reflux 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 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 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
• Increased liver enzymes
• 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):

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

In a clinical trial, the rate of heart attacks with Pradaxa 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 recurrent 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 intestine, rectum, 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 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 esophageal ulcer)
• Inflammation of the esophagus and stomach
• Reflux 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
• Increased liver enzymes

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

• Bleeding may occur at the site of a surgical incision, injection site, or catheter site 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 of white blood cells (which help fight infections)
• Yellowish discoloration of the skin or whites of the eyes, caused by liver or blood problems
• Hair loss

In the clinical trial program, the rate of heart attacks with Pradaxa 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 recurrent 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
• Reflux of gastric juice into the esophagus
• Vomiting
• Feeling like vomiting
• 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):

• Difficulty breathing or wheezing
• Severe allergic reaction that causes difficulty breathing or dizziness
• Severe allergic reaction that causes swelling of the face or throat
• Bleeding
• Bleeding may occur in a joint, wound, surgical incision, injection site, or catheter site in a vein
• Bleeding may occur from hemorrhoids
• Ulcer in the stomach or intestine (including esophageal ulcer)
• 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 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 the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Pradaxa

• The active ingredient is dabigatran. Each hard capsule contains 150 mg of dabigatran etexilate (as mesilate).

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

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

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

Appearance of the Product and Package Contents

Pradaxa 150 mg are hard capsules (approx. 22 × 8 mm) with a light blue opaque cap and a white opaque body. The Boehringer Ingelheim logo is printed on the cap, and the code "R150" is printed on the body of the hard capsule.

This medicine is available in packages containing 10 × 1, 30 × 1, or 60 × 1 hard capsules, a multipack containing 3 packs of 60 × 1 hard capsules (180 hard capsules), or a multipack containing 2 packs of 50 × 1 hard capsules (100 hard capsules) in perforated aluminum unit-dose blisters. Additionally, Pradaxa is available in packages 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 obtain more information on this medicine by contacting 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/.