PRADAXA 110 mg HARD CAPSULES

Introduction

Patient Information: Summary of Product Characteristics

Pradaxa 110 mg hard capsules

dabigatran etexilate

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Pradaxa and what is it used for
2. What you need to know before you take Pradaxa
3. How to take Pradaxa
4. Possible side effects
5. Storing Pradaxa
6. Contents of the pack and other information

1. What is Pradaxa and what is it used for

Pradaxa contains the active substance dabigatran etexilate 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.

Pradaxa is used in adults to:

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

• prevent the formation of blood clots in the brain (stroke) and other blood vessels in the body if you have a type of irregular heartbeat called non-valvular atrial fibrillation and have at least one additional risk factor.

• treat blood clots in the veins of your legs and lungs and to prevent blood clots from forming again in the veins of your legs and lungs.

Pradaxa is used in children to:

• treat and prevent blood clots.

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, recent injury or bleeding in the brain, recent brain or eye surgery).
• if you are prone to bleeding. This tendency can be inherited, of unknown cause, or caused by other medicines.
• if you are taking medicines to prevent blood clots (e.g. warfarin, rivaroxaban, apixaban or heparin), except when switching from one anticoagulant treatment to another, while having a venous or arterial catheter and being administered heparin through this catheter to keep it open, or while your normal 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 a life-threatening liver disease.
• if you are taking oral ketoconazole or itraconazole, medicines used to treat fungal infections.
• if you are taking oral cyclosporine, 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 a mechanical 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 need to undergo surgery.

Tell your doctorif you have or have had any disorder or disease, especially any of the following:

• If you have an increased risk of bleeding, for example:

• if you have recently had bleeding.
• if you have had a tissue removal (biopsy) in the last month.
• if you have had a severe injury (e.g. a bone fracture, a head injury, or any injury that required surgical treatment).
• if you have inflammation of the esophagus or stomach.
• if you have problems with acid reflux in the esophagus.
• 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 bacterial infection of the heart (endocarditis).
• if you know you have reduced kidney function or if you are dehydrated (symptoms include feeling thirsty and passing small amounts of dark-colored urine).
• if you are over 75 years old.
• if you are an adult patient and weigh 50 kg or less.
• only if used in children: if the child has 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 undergo 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 indicated by your doctor.

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

• It is very important that you take 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 anesthesia 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 to decide if it may be necessary to modify the 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 taking Pradaxa 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), except if only applied to the skin
• Medicines used to treat irregular heartbeat (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 depending on the disease for which it was prescribed. See section 3.
• Medicines for the prevention of organ rejection after a transplant (e.g. tacrolimus, cyclosporine)
• 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 breastfeeding

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 tells you it is safe to do so. If you are of childbearing age, you should avoid becoming pregnant during treatment with Pradaxa.

Breastfeeding is not recommended during treatment with Pradaxa.

Driving and using machines

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

3. How to take Pradaxa

Pradaxa capsules can be used in adults and children 8 years of age 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 your doctor's administration instructions for this medication exactly. If in doubt, consult your doctor again.

Take Pradaxa as recommended for the following situations:

Prevention of blood clot formation after knee or hip arthroplasty

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

If your renal function is decreasedby more than half or if you are 75years of age or older, the recommended dose is 150mg once daily(administered in the form of 2 capsules of 75 mg).

If you are using medicines containing amiodarone, quinidine, or verapamil, the recommended dose is 150mg once daily(administered in the form of 2 capsules of 75 mg).

If you are using medicines containing verapamil and your renal function is decreasedby more than half, you should be indicated a reduced dose of Pradaxa of 75mgbecause your risk of bleeding may increase.

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

After knee arthroplasty

You should start treatment with Pradaxa 1-4 hours after the operation, taking a single capsule. Afterward, 2 capsules should be taken once daily for a total of 10 days.

After hip arthroplasty

You should start treatment with Pradaxa 1-4 hours after the operation, taking a single capsule. Afterward, 2 capsules should be taken once daily 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 in the form of one 150mg capsule twice daily.

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

If you are using medicines containing verapamil, you should be indicated a reduced dose of Pradaxa of 220 mg taken in the form of one 110mg capsule twice daily, 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 110mg capsule twice daily.

You can continue taking this medication if it is necessary to restore your normal heart rhythm through a procedure called cardioversion. Take Pradaxa as your doctor has indicated.

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

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 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. It is possible that your doctor will adjust the dose during treatment. Continue using all other medications unless your doctor tells you to stop using one.

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: Pradaxa capsule dosing table

Doses requiring 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 foil.
• Do not peel off the blister foil until the capsule is needed.

Instructions for the bottle

• Press and turn to open.
• After removing the capsule, put the 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 medication 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 arthroplasty

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.

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

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

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

If you 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.

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 fatal, 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.

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

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 be 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
• 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
• Loose or liquid stools
• Feeling like vomiting
• Wound suppuration (discharge of fluid from a surgical wound)
• Increased liver enzymes
• Yellowing 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 be in the brain, at the site of a surgical incision, at the site of injection, or at the site of a catheter in a vein
• Bloody suppuration at 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 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 the available data):

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

Prevention of vascular obstruction in the brain or systemic circulation due to blood clot formation developed after abnormal heart rhythm

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

• Bleeding may be 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
• Loose or liquid stools
• Feeling like vomiting

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

• Bleeding
• Bleeding may be 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 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
• Vomiting
• Difficulty swallowing
• Anomalies in liver function tests

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

• Bleeding may be 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
• Yellowing of the skin or whites of the eyes, caused by liver or blood problems

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

• Difficulty breathing or wheezing
• Decrease in the number or even absence 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 recurrence of blood clots in the veins of the legs and/or lungs

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

• Bleeding may be 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 be in a joint or in a wound
• Bleeding may be 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 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
• Feeling like vomiting
• Vomiting
• Abdominal pain or stomach pain
• Loose or liquid stools
• Anomalies in liver function tests
• Increased liver enzymes

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

• Bleeding may be at the site of a surgical incision, at the site of injection, or at the site of a catheter 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 the available data):

• Difficulty breathing or wheezing
• Decrease in the amount of hemoglobin in the blood (the substance present in red blood cells)
• Decrease in the proportion of blood cells
• Decrease in the number or even absence of white blood cells (which help fight infections)
• Yellowing 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 recurrence of blood clots in children

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

• Decrease in the number of red blood cells in the blood
• Decrease in the number of platelets in the blood
• Skin rash with dark red, prominent, and itchy bumps, caused by an allergic reaction
• Sudden change in skin color and appearance
• Formation of hematomas
• Nosebleeds
• Reflux of gastric juice into the esophagus
• Vomiting
• Feeling like vomiting
• 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 be 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
• Yellowing of the skin or whites of the eyes, caused by liver or blood problems

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

• Lack 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 be in a joint or in a wound, in a surgical incision, at the site of injection, or at the site of a catheter in a vein
• Bleeding may be from hemorrhoids
• Ulcer in the stomach or intestine (including ulcer in the esophagus)
• Anomalies in liver function tests

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide 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 110 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, indigo carmine, and hypromellose.

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

Appearance and Package Contents

Pradaxa 110 mg are hard capsules (approx. 19 × 7 mm) with a light blue opaque cap and a light blue opaque body. The Boehringer Ingelheim logo is printed on the cap and the code "R110" on the body of the hard capsule.

This medicine is available in packs 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. 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 obtain more information about 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/.