Mirexan

Package leaflet: Information for the patient

Mirexan, 150 mg, hard capsules
Dabigatranum etexilatum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

1. What Mirexan is and what it is used for
2. Important information before taking Mirexan
3. How to take Mirexan
4. Possible side effects
5. How to store Mirexan
6. Contents of the pack and other information

1. What Mirexan is and what it is used for

Mirexan contains dabigatran etexilate as the active substance and belongs to a group of medicines called
anticoagulants. It works by blocking a substance in the body responsible for blood clot formation.
Mirexan is used in adults to:

• prevent the formation of blood clots in the brain (stroke) and in other blood vessels in the body in patients who have an irregular heart rhythm called non-valvular atrial fibrillation and at least one additional risk factor.
• treat blood clots in the veins of the legs and lungs, and to prevent recurrence of such clots.

Mirexan is used in children to:

• treat blood clots and prevent their recurrence.

2. Important information before taking Mirexan

When not to use Mirexan

• if the patient is allergic to dabigatran etexilate or any of the other ingredients of this medicine (listed in section 6).
• if the patient has severe impairment of kidney function.
• if the patient is currently experiencing bleeding.
• if the patient has a disease of any internal organ that increases the risk of major bleeding (e.g. stomach ulcer, brain injury or intracranial bleeding, recent brain or eye surgery).
• if the patient has an increased tendency to bleed, which may be congenital, of unknown cause, or caused by taking other medicines.
• if the patient is taking anticoagulant medicines (e.g. warfarin, rivaroxaban, apixaban or heparin), except for: changing anticoagulant therapy, insertion of a venous or arterial catheter, when heparin is administered through the catheter to maintain its patency, or restoring normal heart rhythm using a procedure called catheter ablation in atrial fibrillation.
• if the patient has severe impairment of liver function or liver disease that may lead to death.
• if the patient is taking oral ketoconazole or itraconazole, medicines used to treat fungal infections.
• if the patient is taking oral cyclosporine, a medicine used to prevent rejection of a transplanted organ.
• if the patient is taking dronedarone, a medicine used to treat heart rhythm disorders.
• if the patient is taking a combination medicine containing glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C virus infection.
• if the patient has had a mechanical heart valve implanted, which requires continuous use of blood-thinning medicines.

Warnings and precautions
Before starting treatment with Mirexan, discuss this with your doctor. If symptoms occur during treatment with Mirexan or if the patient has undergone surgery, consult your doctor.
The patient should inform the doctor if they currently have or have previously had any medical conditions or diseases, especially those listed below:

• if the patient has an increased risk of bleeding, such as:
• if the patient has recently experienced bleeding.
• if the patient has undergone a surgical tissue biopsy (biopsy) within the last month.
• if the patient has suffered a serious injury (e.g. bone fracture, head injury, or any injury requiring surgical treatment).
• if the patient has oesophagitis or gastritis.
• if the patient has gastro-oesophageal reflux (regurgitation of stomach acid into the oesophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below “Mirexan and other medicines”.
• if the patient is taking non-steroidal anti-inflammatory drugs such as diclofenac, ibuprofen, piroxicam.
• if the patient has an infection in the heart (bacterial endocarditis).
• if the patient has impaired kidney function or is dehydrated (feeling thirsty, passing small amounts of dark (concentrated) urine).
• if the patient is over 75 years of age.
• if the patient is an adult weighing 50 kg or less.
• only when used in children: if the child has an infection within or around the brain.
• if the patient has previously had a heart attack or has conditions diagnosed to increase the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such a case, use of Mirexan is not recommended.

When to exercise special caution when using Mirexan

• if the patient needs to undergo surgery: In such a case, temporary discontinuation of Mirexan is necessary due to increased risk of bleeding during and immediately after surgery. It is very important to take Mirexan exactly as directed by the doctor before and after surgery.
• if surgery requires insertion of a catheter or injection into the spine (e.g. for epidural or spinal anaesthesia or for pain relief):
• It is very important to take Mirexan exactly as directed by the doctor before and after surgery.
• The patient should immediately inform the doctor if they experience numbness or weakness in the legs or problems with bowel or bladder function after the anaesthesia wears off, as urgent medical care is required.
• if the patient has fallen or sustained an injury during treatment, especially if the head was injured. Immediate medical evaluation is necessary. The doctor will assess whether there is an increased risk of bleeding.
• if the patient has a condition called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), the patient should inform their doctor, who will decide whether treatment needs to be changed.

Mirexan and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take. In particular, tell your doctor before taking Mirexan if you are taking any of the following medicines:

• Medicines that reduce blood clotting (e.g. warfarin, phenprocoumon, acenocoumarol, heparin, clopidogrel, prasugrel, ticagrelor, rivaroxaban, acetylsalicylic acid)
• Medicines used to treat fungal infections (e.g. ketoconazole, itraconazole), unless these medicines are applied only to the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil).
• In patients taking medicines containing verapamil, the doctor will recommend a lower dose of Mirexan. See section 3.
• Medicines used to prevent rejection of a transplanted organ (e.g. tacrolimus, cyclosporine).
• A combination medicine containing glecaprevir and pibrentasvir (an antiviral medicine used to treat hepatitis C virus infection).
• Anti-inflammatory and pain-relieving medicines (e.g. acetylsalicylic acid, ibuprofen, diclofenac).
• St. John’s wort, a herbal medicine used to treat depression.
• Antidepressant medicines known as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors.
• Rifampicin or clarithromycin (both antibiotics).
• Certain antiviral medicines used to treat AIDS (e.g. ritonavir).
• Some medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding
It is not known what effect dabigatran has on pregnancy or the unborn child. Mirexan should not be used during pregnancy unless the doctor determines it is safe. Women of childbearing potential should avoid becoming pregnant while taking Mirexan.
Breastfeeding should not be performed during treatment with Mirexan.

Driving and operating machinery
Mirexan has no effect or has a negligible effect on the ability to drive and operate machinery.

3. How to take Mirexan

Mirexan capsules can be used in adults and children aged 8 years or older who are able to swallow capsules whole. There are other age-appropriate formulations available for treating children under 8 years of age.
This medicine should always be taken exactly as prescribed by the doctor. If in doubt, consult the doctor.
Mirexan should be taken as prescribed in the following conditions:

• to prevent the formation of blood clots in the brain (stroke) and other blood vessels in the patient's body, if the patient has a type of irregular heart rhythm called non-valvular atrial fibrillation and at least one additional risk factor.
• to treat blood clots in the veins of the legs and lungs, and to prevent recurrence of blood clots in the veins of the legs and lungs.

The recommended dose of the medicine is 300 mg taken as one 150 mg capsule twice daily.
In patients aged 80 years or older, the recommended dose of Mirexan is 220 mg taken as one 110 mg capsule twice daily.
Patients taking medicines containing verapamil should take a reduced dose of Mirexan of 220 mg taken as one 110 mg capsule twice daily due to an increased risk of bleeding.
In patients with an increased risk of bleeding, the doctor may recommend administering Mirexan at a dose of 220 mg taken as one 110 mg capsule twice daily.
Treatment with Mirexan may be continued if the patient requires restoration of normal heart function by a procedure called cardioversion or by a procedure called catheter ablation for atrial fibrillation. Mirexan should be taken as directed by the doctor.
In the case of implantation of a medical device (stent) into a blood vessel to maintain its patency using a procedure called percutaneous coronary intervention with stent implantation, the patient may receive treatment with Mirexan after the doctor has confirmed adequate control of blood coagulation. Mirexan should be taken as directed by the doctor.
Treatment of blood clots and prevention of recurrent blood clots in children
Mirexan should be taken twice daily, one dose in the morning and one in the evening, approximately at the same time each day. The interval between doses should be as close as possible to 12 hours.
The recommended dose depends on body weight and age. The doctor will determine the appropriate dose. The doctor may adjust the dose as treatment progresses. All other medications should be continued unless the doctor advises otherwise.
Table 1 shows the single and total daily doses of Mirexan in milligrams (mg).
Doses depend on the patient's weight in kilograms (kg) and age.
Table 1: Mirexan dosing

Single doses requiring combination 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: as two 110 mg capsules
185 mg: as one 75 mg capsule plus one 110 mg capsule
150 mg: as one 150 mg capsule or
two 75 mg capsules

How to take Mirexan
Mirexan can be taken with or without food. The capsules should be swallowed whole,
with a glass of water, to facilitate passage into the stomach. Do not crush,
chew or empty the pellets from the capsule, as this may increase the risk of bleeding.

Switching anticoagulant medication
Do not switch anticoagulant medication without first obtaining detailed instructions from your doctor.

Accidentally taking too much Mirexan
Taking too high a dose of Mirexan increases the risk of bleeding. If a patient has taken too many
Mirexan capsules, contact a doctor immediately. Specific treatment methods are available.

Missed dose of Mirexan
A missed dose of dabigatran etexilate may be taken up to 6 hours before the next scheduled dose.
If less than 6 hours remain before the next scheduled dose, the missed dose should not be taken.
Do not take a double dose to make up for a missed dose.

Stopping Mirexan
Mirexan should be taken as directed by the doctor. Do not stop taking Mirexan without first consulting
your doctor, as the risk of blood clots may increase if treatment is stopped prematurely.
Contact your doctor if you experience indigestion after taking Mirexan.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Mirexan affects the blood clotting system; therefore, most adverse effects are related to symptoms such as bruising or bleeding. The occurrence of major or severe bleeding cannot be ruled out, which is the most serious adverse effect and, regardless of location, may be life-threatening, lead to disability, or even death. In some cases, such bleeding may not be visible.
If bleeding that does not stop spontaneously occurs, or symptoms of excessive bleeding (unusual weakness, fatigue, paleness, dizziness, headache, or unexplained swelling), contact your doctor immediately. The doctor may decide to place the patient under close observation or change the treatment.
In case of severe allergic reactions, which may cause difficulty breathing or dizziness, contact your doctor immediately.

The possible adverse effects listed below are grouped according to their frequency of occurrence:

Prevention of blockage in blood vessels of the brain or other parts of the body caused by blood clots due to irregular heart rhythm.

Common (may occur in up to 1 in 10 patients):

• Bleeding may occur from the nose, into the stomach or intestines, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in the number of red blood cells in the blood
• Abdominal or stomach pain
• Indigestion
• Frequent passage of loose or watery stools
• Nausea

Uncommon (may occur in up to 1 in 100 patients):

• Bleeding
• Bleeding may occur from hemorrhoids, from the rectum, or into the brain
• Formation of a hematoma
• Coughing up blood or blood in sputum
• Decrease in the number of platelets in the blood
• Decrease in hemoglobin levels in the blood (substance in red blood cells)
• Allergic reaction
• Sudden change in skin color and appearance
• Itching
• Stomach or intestinal ulcer (including esophageal ulceration)
• Inflammation of the esophagus and stomach
• Regurgitation of stomach contents into the esophagus (reflux)
• Vomiting
• Difficulty swallowing
• Abnormal laboratory test results indicating liver function

Rare (may occur in up to 1 in 1,000 patients):

• Bleeding into a joint, from a surgical incision site, from a wound, from an injection site, or from the site of intravenous catheter insertion
• Severe allergic reactions causing difficulty breathing or dizziness
• Severe allergic reactions causing swelling of the face or throat
• Skin rash characterized by dark red, raised, itchy nodules due to an allergic reaction
• Decrease in the number of red blood cells in the blood
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver or blood disease

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

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

In clinical trials, the number of heart attacks with Mirexan was numerically higher than with warfarin. The overall number of events was small.

Treatment of blood clots in the legs and lungs, and prevention of recurrence of blood clots in the legs and lungs

Common (may occur in up to 1 in 10 patients):

• Bleeding may occur from the nose, into the stomach or intestines, from the anus, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Indigestion

Uncommon (may occur in up to 1 in 100 patients):

• Bleeding
• Bleeding may occur into a joint or following injury
• Bleeding from hemorrhoids may occur
• Decrease in the number of red blood cells in the blood
• Hematomas
• Coughing up blood or blood-stained sputum
• Allergic reaction
• Sudden change in skin color or appearance
• Itching
• Stomach or intestinal ulcer
• Inflammation of the esophagus and stomach
• Regurgitation of stomach contents into the esophagus (reflux)
• Nausea
• Vomiting
• Abdominal or stomach pain
• Frequent passage of loose or watery stools
• Abnormal liver function parameters in laboratory tests
• Increased liver enzyme activity

Rare (may occur in up to 1 in 1,000 patients):

• Bleeding from a surgical incision site, injection site, or site of intravenous catheter insertion, or bleeding into the brain
• Decrease in the number of platelets in the blood
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash characterized by dark red, raised, itchy nodules due to an allergic reaction
• Difficulty swallowing

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

• Difficulty breathing or wheezing
• Decrease in hemoglobin levels in the blood (substance in red blood cells)
• Decrease in the number of red blood cells in the blood
• Yellowing of the skin or whites of the eyes due to liver or blood disease
• Decrease in number or complete absence of white blood cells (which help fight infections)
• Hair loss

In clinical trials, the number of heart attacks with Mirexan was numerically higher than with warfarin. The overall number of events was low. No difference in the number of heart attacks was demonstrated between patients treated with dabigatran and patients receiving placebo.

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

Common (may occur in up to 1 in 10 individuals):

• Decrease in the number of red blood cells in the blood
• Decrease in the number of platelets in the blood
• Skin rash characterized by dark red, raised, itchy nodules due to an allergic reaction
• Sudden change in skin color and appearance
• Formation of hematomas
• Nosebleeds
• Regurgitation of stomach contents into the esophagus (reflux)
• Vomiting
• Nausea
• Frequent passage of loose or watery stools
• Indigestion
• Hair loss
• Increased liver enzyme activity

Uncommon (may occur in up to 1 in 100 individuals):

• Decrease in the number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, from the brain, from the rectum, from the penis/vagina or urinary tract (including pink or red urine due to presence of blood), or under the skin
• Decrease in hemoglobin levels in the blood (substance in red blood cells)
• Decrease in blood cell proportion
• Itching
• Coughing up blood or blood-stained sputum
• Abdominal or stomach pain
• Inflammation of the esophagus and stomach
• Allergic reaction
• Difficulty swallowing
• Yellowing of the skin or whites of the eyes due to liver or blood disease

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

• Absence of white blood cells (which help fight infections)
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Difficulty breathing or wheezing
• Bleeding
• Bleeding may occur into a joint, from a wound, from a surgical incision site, from an injection site, or from the site of intravenous catheter insertion
• Bleeding from hemorrhoids may occur
• Stomach or intestinal ulcer (including esophageal ulceration)
• Abnormal liver function test results

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Mirexan

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or blister pack following EXP. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Store in the original packaging to protect from moisture.
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Package contents and other information

What Mirexan contains

• The active substance is dabigatran. Each hard capsule contains 150 mg of dabigatran etexilate (as mesylate).
• Other ingredients are: tartaric acid, arabic gum, hypromellose 2910 (15 cps), dimethicone 350 cS, talc and hydroxypropylcellulose (100 cps).
• The capsule shell contains: carrageenan, potassium chloride, titanium dioxide (E 171), hypromellose 2910 (6 cps), indigo carmine (E 132).

What Mirexan looks like and contents of the pack
Mirexan 150 mg is a hard capsule with a blue cap and a white or almost white body, size 0, filled with pellets ranging from almost white to pale yellow.
This medicinal product is available in packs containing 30 or 60 hard capsules in perforated blisters made of Aluminium/OPA/Aluminium/PVC, packed in a cardboard box.
A multipack containing 3 packs of 60 hard capsules (180 hard capsules) in perforated blisters made of Aluminium/OPA/Aluminium/PVC, packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Biofarm Sp. z o.o.
Wałbrzyska Street 13
60-198 Poznań
Poland
Tel.: +48 61 66 51 500
E-mail: [email protected]

Manufacturer
Galenicum Health, S.L.
Avda. Cornellá 144, 7º-1ª Edificio LEKLA,
08950 – Esplugues de Llobregat (Barcelona)
Spain

SAG Manufacturing S.L.U
Crta. N-I, Km 36
28750 San Agustin de Guadalix,
Madrid – Spain

Biofarm Sp. z o.o.
Wałbrzyska Street 13,
60-198 Poznań
Poland

For more detailed information, please contact the local representative of the Marketing Authorisation Holder.

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Malta Mirexan 150 mg hard capsules
Mirexan 110 mg hard capsules
Mirexan 75 mg hard capsules
Poland Mirexan, 75 mg, hard capsules
Mirexan, 110 mg, hard capsules
Mirexan, 150 mg, hard capsules

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/ and on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.