Mirexan

Package leaflet: Information for the patient

Mirexan, 75 mg, hard capsules
Dabigatranum etexilatum
Please read carefully the entire leaflet before taking the medicine, as it contains
important information for the patient.

• 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 share it with others. The medicine may harm another person, 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.

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 that is responsible for blood clot formation.
Mirexan is used in adults to:

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

Mirexan is used in children to:

• treat blood clots and to prevent recurrence of blood clots.

2. Important information before taking Mirexan

When not to take 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 kidney function impairment.

• 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 brain or eye surgery).

• if the patient has an increased tendency to bleed. This 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 when switching anticoagulant therapy, inserting a venous or arterial catheter where heparin is administered through the catheter to maintain patency, or restoring normal heart rhythm using a procedure called catheter ablation in atrial fibrillation.

• if the patient has severe liver function impairment 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 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 this medicine or if the patient has undergone surgery, medical advice should be sought.
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 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 inflammation of the oesophagus or stomach.
• if the patient has gastro-oesophageal reflux (acid reflux into the oesophagus).
• if the patient is taking medicines that may increase the risk of bleeding. See below “Mirexan with 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 reduced kidney function or is dehydrated (feeling thirsty and passing reduced amounts of dark (concentrated) or frothy 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 around or within the brain.
• if the patient has had a previous heart attack or if the patient has been diagnosed with conditions increasing the risk of heart attack.
• if the patient has liver disease affecting blood test results. In such cases, use of this medicine is not recommended.

When to exercise particular caution when taking 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 exactly as directed by the doctor before and after surgery.
• if surgery involves 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 numbness or weakness in the legs or problems with bowel or bladder function occur after the anaesthetic 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 attention should be sought. The doctor will assess whether there may be 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 the doctor, who will decide whether a change in treatment is necessary.

Mirexan with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. In particular, tell the doctor before taking Mirexan if the patient is 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 only to the skin.
• Medicines used to treat heart rhythm disorders (e.g. amiodarone, dronedarone, quinidine, verapamil). For patients taking medicines containing amiodarone, quinidine or verapamil, the doctor may recommend a lower dose of Mirexan depending on the condition for which it was prescribed. See also section 3.
• Medicines used to prevent rejection of a transplanted organ (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).
• Antiviral medicines used to treat AIDS (e.g. ritonavir).
• Certain medicines used to treat epilepsy (e.g. carbamazepine, phenytoin).

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

Driving and operating machinery
Mirexan has no effect or 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 formulations are available for the treatment of children under 8 years of age.
This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor.
Take Mirexan exactly as directed below:
Prevention of blood clots after hip or knee replacement surgery
The recommended dose is 220 mg once daily (taken as 2 capsules of 110 mg).
In patients with renal function 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).
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).
Patients taking medicines containing verapamil, who also have renal function reduced by more than half, should take a reduced dose of Mirexan of 75 mg due to an increased risk of bleeding.
In both types of surgery, treatment should not be initiated if there is active bleeding at the surgical site. If treatment cannot be started by the day after surgery, it should be initiated with a dose of 2 capsules once daily.
After knee replacement surgery
Initiate Mirexan with one capsule taken 1 to 4 hours after completion of surgery. Then take 2 capsules once daily for a total of 10 days.
After hip replacement surgery
Initiate Mirexan with one capsule taken 1 to 4 hours after completion of surgery. Then take 2 capsules once daily for a total of 28 to 35 days.
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 be as close as possible to 12 hours.
The recommended dose depends on body weight and age. Your doctor will determine the correct dose and may adjust it during treatment. Continue taking all other prescribed medicines unless your doctor 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, crush, or empty the pellets from the capsule, as this may increase the risk of bleeding.

Changing anticoagulant therapy
Do not change anticoagulant medication without receiving detailed instructions from your doctor.

Accidental overdose of Mirexan
Taking too high a dose of this medicine increases the risk of bleeding. If a patient has taken too many capsules, contact a doctor immediately. Specific treatment methods are available.

Missed dose of Mirexan
Prevention of blood clots after hip or knee 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.

Treatment and prevention of recurrent blood clots in children
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, do not take the missed dose.
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 this medicine without consulting your doctor first, as the risk of developing blood clots may be higher if treatment is stopped prematurely. Contact your doctor if gastrointestinal discomfort occurs after taking Mirexan.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Mirexan affects the blood clotting system, therefore most of the adverse reactions are related to
symptoms such as bruising or bleeding. Severe or extensive bleeding may occur, which is the most
serious adverse reaction, and regardless of location, it may lead to disability, be life-threatening, or even result in death. In some cases, these bleedings may not be visible.
If bleeding that does not stop spontaneously or symptoms of excessive bleeding occur (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 a serious allergic reaction, which may cause difficulty breathing or dizziness, contact your doctor immediately.

The possible side 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 people):

• Decreased haemoglobin levels in the blood (the substance in red blood cells)
• Abnormal liver function test results

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

• Bleeding may occur from the nose, stomach or intestines, penis/vagina or urinary tract (including pink or red urine due to presence of blood), from haemorrhoids, from the rectum, under the skin, into joints, due to injury or after injury or surgical procedure
• Formation of haematomas or bruising occurring after surgical procedure
• Blood in stool detected in laboratory tests
• Decreased number of red blood cells in blood
• Decreased blood cell count
• Allergic reaction
• Vomiting
• Frequent passage of loose or liquid stools
• Nausea
• Discharge from wound (fluid leaking from surgical wound)
• Increased liver enzyme activity
• Yellowing of the skin or whites of the eyes caused by liver or blood disease

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

• Bleeding
• Bleeding 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
• Decreased platelet count in blood
• Decreased number of red blood cells in blood 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 occurring as a result of an allergic reaction
• Sudden change in skin colour and appearance
• Itching
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Inflammation of the oesophagus and stomach
• Regurgitation of food from the stomach into the oesophagus (reflux)
• Abdominal pain or stomach pain
• Indigestion
• Difficulty swallowing
• Discharge of fluid from wound
• Discharge of fluid from surgical wound

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

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

Treatment and prevention of recurrence of blood clots in children
Common (may occur in up to 1 in 10 people):

• Decreased number of red blood cells in blood
• Decreased platelet count in blood
• Skin rash consisting of dark red, raised, itchy bumps occurring as a result of an allergic reaction
• Sudden change in skin colour and appearance
• Formation of haematomas
• Nosebleeds
• Regurgitation of food from the stomach into the oesophagus (reflux)
• Vomiting
• Nausea
• Frequent passage of loose or liquid stools
• Indigestion
• Hair loss
• Increased liver enzyme activity

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

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

Frequency not known (frequency cannot be estimated from the 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 into joints, from wounds, from surgical incision sites, injection sites or intravenous catheter insertion sites
• Bleeding from haemorrhoids
• Stomach or intestinal ulcer (including oesophageal ulceration)
• Abnormal liver function test results

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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 49-21309,
Website: https://smz.ezdrowie.gov.pl .
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of the medicine.

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 outer carton or
blister: Expiry (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. Contents of the pack and other information

What Mirexan contains

• The active substance is dabigatran. Each hard capsule contains 75 mg of dabigatran etexilate (as mesilate).
• The other ingredients are: tartaric acid, gum arabic, hypromellose 2910 (15 cps), dimethicone 350 cS, talc and hydroxypropylcellulose (100 cps).
• The capsule shell contains carrageenan, potassium chloride, titanium dioxide (E 171) and hypromellose 2910 (6 cps).

What Mirexan looks like and contents of the pack
Mirexan 75 mg is white or almost white hard capsules of size 2, filled with pellets ranging in colour from almost white to pale 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.
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 more detailed 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 medicine 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.