DABIGATRAN ETEXILATE ACCORD 150 mg HARD CAPSULES

2. What you need to know before you take Dabigatran Etexilate Accord

Do not take Dabigatran Etexilate Accord

• 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 any disease in an organ of the body that increases the risk of severe bleeding (e.g. stomach ulcer, 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 clotting (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

Talk to your doctor before you start taking Dabigatran Etexilate Accord. During treatment with this medicine, you may also need to talk to your doctor if you experience any symptoms or if you are going 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 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 oesophagus or stomach.
• if you have problems with acid reflux in the oesophagus.
• if you are taking medicines that may increase the risk of bleeding. See Other medicines and Dabigatran Etexilate Accord 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 Dabigatran Etexilate Accord

• If you are going to have surgery:

In this case, Dabigatran Etexilate Accord should be temporarily stopped due to an increased risk of bleeding during and after surgery. It is very important that you take Dabigatran Etexilate Accord 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 Dabigatran Etexilate Accord 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 a doctor to examine you, as you may have a higher 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 Dabigatran Etexilate Accord

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 Dabigatran Etexilate Accord 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 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 verapamil, your doctor may tell you to use a reduced dose of Dabigatran Etexilate Accord depending on the disease for which it has 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)
• Pain-relieving and anti-inflammatory medicines (e.g. aspirin, ibuprofen, diclofenac)
• St John's Wort (Hypericum perforatum), 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 Dabigatran Etexilate Accord on pregnancy and the foetus 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 potential, you should avoid becoming pregnant during treatment with Dabigatran Etexilate Accord.

Breast-feeding is not recommended during treatment with Dabigatran Etexilate Accord.

Driving and using machines

Dabigatran Etexilate Accord has no known effects on the ability to drive or use machines.

Dabigatran Etexilate Accord contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule, which means it is essentially “sodium-free”.

3. How to take Dabigatran Etexilate Accord

Dabigatran Etexilate Accord hard capsules can be used in adults and children aged 8 years or older who are able to swallow the capsules whole. There are other pharmaceutical forms suitable for the treatment of children under 8 years.

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

Take Dabigatran Etexilate Accord as recommended for the following situations:

Prevention of vascular cerebral or systemic obstruction by blood clot formation developed after irregular heartbeat and treatment of blood clots in the veins of your legs and lungs, including prevention of them happening again in the veins of your legs and lungs

The recommended dose is 300 mg given as one 150 mg capsule twice a day.

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

If you are using medicines that contain verapamil, you should be told to use a reduced dose of Dabigatran Etexilate Accord of 220 mg taken as one 110 mg capsule twice a day, 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 110 mg capsule twice a day.

You can continue taking this medicine if you need to restore your normal heartbeat through a procedure called cardioversion or through a procedure called catheter ablation for atrial fibrillation. Take Dabigatran Etexilate Accord as told 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 Dabigatran Etexilate Accord once your doctor has decided that normal blood clotting control has been achieved. Take Dabigatran Etexilate Accord as told by your doctor.

Treatment of blood clots and prevention of them happening again in children

Dabigatran Etexilate Accord 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. Continue using all other medicines unless your doctor tells you to stop using any.

Table 1 shows the single dose and total daily doses of Dabigatran Etexilate Accord in milligrams (mg) to be administered. The doses depend on the patient's weight in kilograms (kg) and age in years.

Doses that require combinations of more than one capsule:

How to take Dabigatran Etexilate Accord

Dabigatran Etexilate Accord 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.

Changing anticoagulant treatment

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

If you take more Dabigatran Etexilate Accord 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. There are specific treatment options available.

If you forget to take Dabigatran Etexilate Accord

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 Dabigatran Etexilate Accord

Take Dabigatran Etexilate Accord 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 higher if you stop treatment too soon. Contact your doctor if you experience indigestion after taking Dabigatran Etexilate Accord.

If you have any other 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.

Dabigatran etexilate Accord 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 bleeds 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 vascular cerebral or systemic obstruction by 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
• Gastroesophageal reflux
• Vomiting
• Difficulty swallowing
• Abnormalities 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 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 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 available data):

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

In a clinical trial, the rate of heart attacks with Dabigatran etexilate Accord was numerically higher than with warfarin. The overall incidence was low.

Treatment of blood clots in the veins of the legs and lungs, including prevention of recurrence of blood clots in the veins of the legs and/or lungs

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

• Bleeding may occur from the nose, stomach, or 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 in a 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
• Gastroesophageal reflux
• Feeling like vomiting
• Vomiting
• Abdominal pain or stomach pain
• Frequent loose or liquid stools
• Abnormalities 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, or at the site of an 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 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 leukocytes (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 Dabigatran etexilate Accord was higher than with warfarin. The overall incidence was low. No imbalance was observed in the rate of heart attacks 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 physical appearance
• Formation of hematomas
• Nasal bleeding
• Gastroesophageal reflux
• 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 leukocytes (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
• Yellowing 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 leukocytes (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 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 intestine (including esophageal ulcer)
• Abnormalities 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 prospectus. 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 Dabigatran etexilate Accord

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.

Store at temperatures below 30°C.

After opening for the first time, the bottle can be used for a maximum of 60 days.

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 Dabigatran etexilate Accord

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

• The other ingredients are tartaric acid, hypromellose (E464), talc (E553b), hydroxypropylcellulose (E463), croscarmellose sodium (E468), magnesium stearate (E572) (see section 2 "Dabigatran etexilate Accord contains sodium").

• The capsule shell contains titanium dioxide (E171) and hypromellose (E464)

• The black printing ink contains shellac (E904), propylene glycol (E1520), iron oxide black (E172), potassium hydroxide (E525).

Appearance and Package Contents of Dabigatran etexilate Accord

Dabigatran etexilate Accord 150 mg is a hard capsule, size "0" (approx. 22 x 8 mm), with an opaque white cap with "MD" printed and an opaque white body with "150" printed in black ink, containing a mixture of white to light yellow pellets and light yellow granules.

Dabigatran etexilate Accord 150 mg hard capsules are available in blister packs of OPA/Alu/desiccant PE-PET/Alu/PE containing 10, 30, 60, and 180 capsules per carton.

Dabigatran etexilate Accord 150 mg hard capsules are available in unit dose blister packs of OPA/Alu/desiccant PE-PET/Alu/PE containing 10 x 1, 30 x 1, 60 x 1, and 180 x 1 capsules per carton.

Dabigatran etexilate Accord 150 mg hard capsules are available in bottles of polypropylene with a child-resistant cap containing 60 capsules per carton.

Not all pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6a Planta,

Barcelona, 08039

Spain

Manufacturer

Accord Healthcare Polska Sp. z.o.o.

ul.Lutomierska 50,

95-200, Pabianice, Poland

Pharmadox Healthcare Limited

KW20A Kordin Industrial Park,

Paola PLA 3000, Malta

Accord Healthcare B.V.

Winthontlaan 200,

3526 KV Utrecht, Netherlands

Date of Last Approval of this Prospectus:

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