Mirexan

Package leaflet: Information for the patient

Mirexan, 110 mg, hard capsules
Dabigatranum etexilatum
Please read carefully the entire leaflet before taking this medicine, as it contains
important information for the patient.

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

Table of 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 for:

• preventing the formation of blood clots in veins after hip or knee replacement surgery.
• preventing blood clots in the brain (stroke) and in other blood vessels in the body in patients who have a type of irregular heart rhythm called non-valvular atrial fibrillation and at least one additional risk factor.
• treating blood clots in the veins of the legs and lungs and preventing recurrence of blood clots in the veins of the legs and lungs.

Mirexan is used in children for:

• treatment of blood clots and prevention of 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. gastric ulcer, brain injury or intracranial haemorrhage, recent surgery of the brain or eyes).
• 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), with the exception of: switching anticoagulant therapy, insertion of an intravenous or arterial catheter, when heparin is administered through the catheter to maintain its patency, or restoration of normal heart rhythm by 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 fixed-dose combination medicine containing glecaprevir and pibrentasvir, an antiviral medicine used to treat hepatitis C virus infection.
• if the patient has a mechanical heart valve, requiring lifelong anticoagulant therapy.

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 a doctor.
The patient should inform the doctor if they currently have or have previously had any medical conditions or diseases, especially the following:

• 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 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 gastroesophageal reflux (acid reflux 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 (NSAIDs) such as diclofenac, ibuprofen, piroxicam.
• if the patient has an infection in the heart (bacterial endocarditis).
• if the patient has impaired kidney function, or if the patient is dehydrated (feeling thirsty, passing small amounts of dark (concentrated) urine).
• if the patient is over 75 years of age.
• if the patient weighs 50 kg or less.
• only when used in children: if the child has an infection around or within the brain.
• if the patient has had a heart attack or if the patient has been diagnosed with conditions that increase the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such cases, 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 the increased risk of bleeding during and immediately after surgery. It is very important to take Mirexan before and after surgery exactly as directed by the doctor.

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

• It is very important to take Mirexan before and after surgery exactly as directed by the doctor.

• 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 anaesthetic wears off, as urgent medical care may be needed.

• if the patient has fallen or sustained an injury during treatment, especially if the head was injured. Immediate medical evaluation is required. The doctor will assess whether there is an increased risk of bleeding.

• if the patient has a condition called antiphospholipid syndrome (an autoimmune disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether a change in treatment is necessary.

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, before taking Mirexan, tell your doctor 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 are applied topically to the skin only.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). In patients taking medicines containing amiodarone, quinidine or verapamil, the doctor may recommend a lower dose of Mirexan depending on the condition for which it has been prescribed. See section 3.
• Medicines used to prevent rejection of transplanted organs (e.g. tacrolimus, cyclosporine).
• A fixed-dose 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).
• Some medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

Pregnancy and breastfeeding
It is not known what effect dabigatran has on pregnancy and the unborn child. Mirexan should not be used during pregnancy unless the doctor determines it is safe. Women of childbearing potential should use effective contraception during treatment with Mirexan.
Breastfeeding is not recommended 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. Other age-appropriate pharmaceutical forms are available for treating children under 8 years of age.
This medicine should always be taken as directed by the physician. If in doubt, consult your doctor.
Mirexan should be taken according to the following instructions:

Prevention of blood clots after knee or hip joint replacement surgery
The recommended dose is 220 mg once daily (taken as 2 capsules of 110 mg each).
If renal function is reduced by more than half, or in patients aged 75 years or older, the recommended dose is 150 mg once daily (taken as 2 capsules of 75 mg each).
In patients taking medicines containing amiodarone, quinidine, or verapamil, the recommended dose of Mirexan is 150 mg once daily (taken as 2 capsules of 75 mg each).
Patients taking verapamil-containing medicines who also have reduced renal function by more than half should take a reduced dose of 75 mg of Mirexan due to an increased risk of bleeding.

In both types of surgery, treatment should not be initiated if there is bleeding from the surgical site. If treatment cannot be started on the day following surgery, it should be initiated with a dose of 2 capsules once daily.

After knee joint replacement surgery
Treatment with Mirexan should begin with one capsule taken 1 to 4 hours after completion of the surgical procedure. Then, 2 capsules should be taken once daily for a total of 10 days.

After hip joint replacement surgery
Treatment with Mirexan should begin with one capsule taken 1 to 4 hours after completion of the surgical procedure. Then, 2 capsules should be taken once daily for a total of 28 to 35 days.

Prevention of blood clots in blood vessels of the brain and body due to irregular heart rhythm, and treatment and prevention of recurrence of blood clots in leg veins and lungs
The recommended dose 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 verapamil-containing medicines 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 physician may recommend treatment with 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 rhythm through a procedure called cardioversion. Mirexan should be taken as directed by the physician.

In patients undergoing implantation of a medical device (stent) into a blood vessel to maintain its patency using a procedure known as percutaneous coronary intervention with stent implantation, treatment with Mirexan may be initiated once the physician confirms adequate control of blood coagulation. Mirexan should be taken as directed by the physician.

Treatment 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 ideally be 12 hours.

The recommended dose depends on body weight and age. The physician will determine the correct dose and may adjust it during treatment. All other medications should be continued unless the physician advises otherwise.

Table 1 shows the single and total daily doses of Mirexan in milligrams (mg). Doses depend on the patient's body weight in kilograms (kg) and age in years.

Table 1: Dosing of Mirexan capsules

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 break, 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.

Taking more Mirexan than prescribed
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
Prevention of blood clots after knee or hip replacement surgery
Continue taking the missed daily dose of Mirexan at the usual time on the following day.
Do not take a double dose to make up for a missed dose.

Use in adults: Prevention of blood clots in blood vessels of the brain and body by preventing formation of clots caused by irregular heart function, and treatment and prevention of recurrence of blood clots in the veins of the legs and lungs
Use in children: Treatment of blood clots and prevention of recurrent blood clots

A missed dose 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 treatment
Mirexan should be taken according to the doctor's instructions. Do not stop taking Mirexan without first consulting your doctor, as the risk of developing a blood clot may be higher if treatment is stopped prematurely. Contact your doctor if gastrointestinal discomfort occurs after taking Mirexan.

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

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
Mirexan affects the blood clotting system; therefore, most adverse effects involve symptoms such as bruising or bleeding. The occurrence of major or severe bleeding cannot be ruled out, which represent the most serious adverse effects and, regardless of location, may threaten the patient's life, lead to disability, or even death. In some cases, these bleedings may not be visible.
If bleeding occurs that does not stop spontaneously, 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 medication.
In case of serious allergic reactions, which may cause difficulty breathing or dizziness, contact your doctor immediately.
Possible adverse effects listed below are grouped according to their frequency of occurrence:

Prevention of blood clots after hip or knee replacement surgery
Common (may occur in up to 1 in 10 patients):

• Decrease in haemoglobin levels in blood (substance in red blood cells)
• Abnormal liver function test results in laboratory tests

Uncommon (may occur in up to 1 in 100 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), from haemorrhoids, from the rectum, under the skin, into a joint, following injury, after injury, or after a surgical procedure
• Bruising or haematomas occurring after surgical procedure
• Blood in stool detected in laboratory tests
• Decrease in number of red blood cells in blood
• Decrease in proportion of red blood cells in blood
• Allergic reaction
• Vomiting
• Frequent passage of loose or liquid stool
• Nausea
• Discharge from wound (fluid oozing from surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes due to liver or blood problems

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

• Bleeding
• Bleeding may occur into the brain, from the surgical incision site, from the injection site, or from the site of intravenous catheter insertion
• Blood-tinged discharge from the site of intravenous catheter insertion
• Coughing up blood or blood-stained sputum
• Decrease in number of platelets in blood
• Decrease in number of red blood cells after surgical procedure
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash consisting of dark red, raised, itchy bumps due to allergic reaction
• Sudden change in skin colour or appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Abdominal or stomach pain
• Indigestion
• Difficulty swallowing
• Fluid discharge from wound
• Fluid discharge from surgical wound

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

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

Prevention of blood vessel blockage in the brain or other organs due to clots caused by heart rhythm disorders
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 number of red blood cells in blood
• Abdominal or stomach pain
• Indigestion
• Frequent passage of loose or liquid stool
• Nausea

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

• Bleeding
• Bleeding may occur from haemorrhoids, from the rectum, into the brain
• Haematoma formation
• Coughing up blood or blood in sputum
• Decrease in number of platelets in blood
• Decrease in haemoglobin levels in blood (substance in red blood cells)
• Allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Vomiting
• Difficulty swallowing
• Abnormal liver function test results

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

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

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

• Difficulty breathing or wheezing

In clinical trials, the number of heart attacks with dabigatran etexilate 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 recurrent 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 may occur from haemorrhoids
• Decrease in number of red blood cells in blood
• Bruising
• Coughing up blood or blood-stained sputum
• Allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer
• Inflammation of oesophagus and stomach
• Regurgitation of stomach contents into the oesophagus (reflux)
• Nausea
• Vomiting
• Abdominal or stomach pain
• Frequent passage of loose or liquid stool
• Abnormal liver function test results
• Increased liver enzyme activity

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

• Bleeding may occur from the surgical incision site, from the injection site, or from the site of intravenous catheter insertion, or bleeding from the brain
• Decrease in number of platelets in blood
• Severe allergic reaction causing difficulty breathing or dizziness
• Severe allergic reaction causing swelling of the face or throat
• Skin rash consisting of dark red, raised, itchy bumps due to allergic reaction
• Difficulty swallowing
• Decrease in proportion of red blood cells in blood

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

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

In clinical trials, the number of heart attacks with dabigatran etexilate 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 number of red blood cells in blood
• Decrease in number of platelets in blood
• Skin rash consisting of dark red, raised, itchy bumps due to allergic reaction
• Sudden change in skin colour and appearance
• Formation of haematomas
• Nosebleeds
• Regurgitation of stomach contents into the oesophagus (reflux)
• Vomiting
• Nausea
• Frequent passage of loose or liquid stool
• Indigestion
• Hair loss
• Increased liver enzyme activity

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

• Decrease in number of white blood cells (which help fight infections)
• Bleeding may occur into the stomach or intestines, into 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 haemoglobin levels in blood (substance in red blood cells)
• Decrease in proportion of blood cells
• Itching
• Coughing up blood or blood-stained sputum
• Abdominal or stomach pain
• Inflammation of oesophagus 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 the surgical incision site, from the injection site, or from the site of intravenous catheter insertion
• Bleeding may occur from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +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 authorisation holder.
By reporting adverse effects, more information on the safety of this medicine can be collected.

5. How to store Mirexan

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

6. Contents of the pack and other information

What Mirexan contains

• The active substance is dabigatran. Each hard capsule contains 110 mg of dabigatran etexilate (as mesilate).
• Other ingredients are: tartaric acid, acacia 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), and indigotine (E 132).

What Mirexan looks like and contents of the pack
Mirexan 110 mg is a blue, hard capsule of size 1, filled with pellets ranging in colour from almost white to light yellow.
This medicinal product is available in packs containing 10, 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.
ul. Wałbrzyska 13
60-198 Poznań
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.
ul. Wałbrzyska 13,
60-198 Poznań
Poland

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

This medicinal product is authorised in the European Economic Area countries 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 European Medicines Agency website: http://www.ema.europa.eu/ and on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.