MIBREX

Package leaflet: Information for the patient

Mibrex, 2.5 mg, coated tablets
Rivaroxaban
Please read the entire leaflet carefully before using 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 further 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 similar.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Mibrex is and what it is used for

You have been prescribed Mibrex because:

• You have been diagnosed with acute coronary syndrome (a condition including heart attack and unstable angina, i.e. acute chest pain) and elevated levels of cardiac biomarkers have been confirmed. Mibrex reduces the risk of subsequent heart attack or the risk of death due to heart or blood vessel disease in adults. Mibrex will not be given to you as the only medication. Your doctor will also prescribe you to take:
  • acetylsalicylic acid, or
  • acetylsalicylic acid and clopidogrel or ticlopidine.
• You have been diagnosed with a high risk of blood clots due to coronary artery disease or peripheral arterial disease causing symptoms. Mibrex reduces the risk of blood clots (atherothrombotic events) in adults. Mibrex will not be given to you as the only medication. Your doctor will also prescribe acetylsalicylic acid. In certain cases, if you are receiving Mibrex after a procedure to unblock a narrowed or blocked artery in the lower limb to restore blood flow, your doctor may also prescribe clopidogrel to be taken in addition to acetylsalicylic acid for a short period.

Mibrex contains the active substance rivaroxaban and belongs to a group of medicines called anticoagulants. It works by blocking a blood clotting factor (factor Xa), thereby reducing the tendency to form blood clots.

2. Important information before using Mibrex

When not to use Mibrex:

• if the patient is allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6),
• if the patient has excessive bleeding,
• if the patient has a disease or condition of an organ leading to an increased risk of serious bleeding (e.g. stomach ulcer, injury or bleeding into the brain, recent brain or eye surgery),
• if the patient is taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when switching anticoagulant therapy or if heparin is administered to maintain the patency of a venous or arterial catheter,
• if the patient has been diagnosed with acute coronary syndrome and previously experienced bleeding or blood clot in the brain (stroke),
• if the patient has been diagnosed with coronary artery disease or peripheral arterial disease and previously had a brain hemorrhage (stroke) or occlusion of small arteries supplying blood to tissues in deep brain structures (lacunar stroke), or if the patient had a blood clot in the brain (ischemic, non-lacunar stroke) within the last month,
• if the patient has a liver disease that increases the risk of bleeding,
• if the patient is pregnant or breastfeeding. Do not use Mibrex, and inform the doctor if the patient suspects any of the above conditions.

Warnings and precautions
Before starting treatment with Mibrex, discuss this with the doctor or pharmacist. Mibrex should not be used in combination with other blood-thinning medicines besides acetylsalicylic acid, clopidogrel, or ticlopidine, such as prasugrel or ticagrelor.
Special caution is required when using Mibrex:

• if the patient has an increased risk of bleeding, including in the following conditions:
  • severe kidney disease, as kidney function may affect the amount of medicine acting in the patient's body,
  • taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is administered to maintain the patency of a venous or arterial catheter (see section "Mibrex with other medicines"),
  • blood clotting disorders,
  • very high blood pressure that does not decrease despite medication,
  • stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestines and stomach or esophagitis (throat and esophagus), e.g. due to gastroesophageal reflux disease (backflow of stomach acid into the esophagus), or tumors located in the stomach, intestines, genital or urinary system,
  • blood vessel disease in the posterior part of the eyeball (retinopathy),
  • lung disease with dilated bronchi filled with pus (bronchiectasis) or previous lung bleeding,
  • if the patient is over 75 years of age,
  • if the patient weighs less than 60 kg,
  • coronary artery disease with severe symptomatic heart failure,
• in patients with prosthetic heart valves,
• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment adjustment is necessary.

If the patient suspects any of the above conditions, the doctor should be informed
before using Mibrex. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the patient needs surgery:

• strictly follow the doctor's instructions regarding the timing of taking Mibrex before or after surgery,
• if catheterization or spinal puncture (e.g. for epidural or intrathecal anesthesia or pain relief) is planned during surgery:
  • it is very important to take Mibrex before and after the puncture or catheter removal, as directed by the doctor;
  • due to the need for special caution, the doctor should be informed immediately if numbness or weakness in the legs, or disturbances in bowel or bladder function occur after anesthesia.

Children and adolescents
Mibrex 2.5 mg tablets are not recommended for patients under 18 years of age. There is insufficient data on the use of this medicine in children and adolescents.
Mibrex with other medicines
Inform the doctor or pharmacist about all medicines currently or recently taken, including those obtained without a prescription.

• If the patient is taking certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are used only topically on the skin, ketoconazole tablets (used in the treatment of Cushing's syndrome, in which the body produces too much cortisol), certain antibacterial medicines (e.g. clarithromycin, erythromycin), certain antiviral medicines used in HIV infection or AIDS treatment (e.g. ritonavir), other medicines used to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin or acenocoumarol, prasugrel and ticagrelor (see section "Warnings and precautions")), anti-inflammatory and pain medicines (e.g. naproxen or acetylsalicylic acid), dronedarone, a medicine used to treat heart rhythm disorders, certain medicines used to treat depression (selective serotonin reuptake inhibitors (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)). If the patient suspects any of the above conditions, the doctor should be informed before using Mibrex, as the effect of Mibrex may be enhanced. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring. If the doctor considers that the patient has an increased risk of developing stomach or intestinal ulcers, preventive treatment may be prescribed.

If the patient is taking
certain medicines used to treat epilepsy (phenytoin, carbamazepine, phenobarbital),
St. John's wort ( Hypericum perforatum ), a herbal medicine used for depression,
or rifampicin, which belongs to the group of antibiotics.
If the patient suspects any of the above conditions, the doctor should be informed
before using Mibrex, as the effect of Mibrex may be reduced. The doctor will decide whether to use Mibrex and whether the patient requires particularly close monitoring.
Pregnancy and breastfeeding
Do not use Mibrex if the patient is pregnant or breastfeeding. If there is a risk that the patient may become pregnant, an effective method of contraception should be used during treatment with Mibrex. If the patient becomes pregnant while taking this medicine, she should immediately inform the doctor, who will decide on further treatment.
Driving and operating machinery
Mibrex may cause dizziness (common side effects) or fainting (uncommon side effects) (see section 4 "Possible side effects"). Patients experiencing these side effects should not drive, ride a bicycle, or operate tools or machinery.
Mibrex contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult the doctor before taking this medicine.
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the product is considered "sodium-free".

3. How to take Mibrex

This medicine should always be taken as directed by the doctor. If in doubt,
consult the doctor or pharmacist.
How many tablets to take
The recommended dose is one 2.5 mg tablet twice daily. Mibrex should be taken at approximately
the same time each day (for example, one tablet in the morning and one in the evening). This medicine
can be taken with or without food.
If a patient has difficulty swallowing the whole tablet, discuss alternative ways of taking Mibrex with
the doctor. The tablet may be crushed and mixed with water or apple puree immediately before
administration. If necessary, the doctor may administer crushed Mibrex tablets via a gastric tube.
Mibrex will not be given to the patient as the sole medication.
The doctor will prescribe acetylsalicylic acid for the patient to take. If the patient is receiving Mibrex
after an acute coronary syndrome, the doctor may also prescribe clopidogrel or ticlopidine.
If the patient is receiving Mibrex following a procedure to restore blood flow through a narrowed or
blocked artery in the lower limb, the doctor may also prescribe clopidogrel for a short period in
addition to acetylsalicylic acid.
The doctor will inform the patient about the dose of these medications to take (usually 75–100 mg of
acetylsalicylic acid daily, or a daily dose of 75–100 mg acetylsalicylic acid plus a daily dose of 75 mg
clopidogrel, or the standard daily dose of ticlopidine).
When to start taking Mibrex
Treatment with Mibrex after acute coronary syndrome should be initiated as soon as possible after
stabilization of the acute event, no earlier than 24 hours after hospital admission,
and at the time when parenteral (by injection) anticoagulant treatment would normally be discontinued.
The doctor will inform the patient when to start treatment with Mibrex if coronary artery disease or
peripheral arterial disease has been diagnosed.
The doctor will decide how long treatment should continue.
Taking more Mibrex than prescribed
If a patient has taken more Mibrex than prescribed, contact the doctor immediately. Taking too high
a dose of Mibrex increases the risk of bleeding.
If a dose of Mibrex is missed
Do not take a double dose to make up for a missed dose. If a dose is missed, take the next dose at
the scheduled time.
Stopping Mibrex treatment
Mibrex should be taken regularly and for the duration prescribed by the doctor.
Do not stop taking Mibrex without first consulting the doctor. Stopping treatment with this medicine
may increase the risk of another heart attack, stroke, or death due to heart or blood vessel disease.
If there are any further questions about the use of this medicine, consult the doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Like other medicines with a similar effect in reducing blood clot formation, Mibrex
can cause bleeding, which may potentially be life-threatening. Excessive bleeding
may lead to a sudden drop in blood pressure (shock). Signs of bleeding are not always obvious
or visible.
You should contact your doctor immediately if any of the following adverse effects occur:

• Signs of bleeding:
  • bleeding into the brain or inside the skull (symptoms may include headache, one-sided paralysis, vomiting, seizures, reduced level of consciousness, and neck stiffness. This is a serious medical emergency. Seek immediate medical help!),
  • prolonged or excessive bleeding,
  • unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain, or angina. Your doctor may decide that close monitoring or a change in treatment is necessary.
• Signs of severe skin reactions:
  • widespread, acute skin rash, blistering, or mucosal lesions (e.g., in the mouth or eyes) (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), characterized by rash, fever, internal organ inflammation, hematological disorders, and systemic involvement. The frequency of these adverse effects is very rare (affecting up to 1 in 10,000 people).
• Signs of serious allergic reactions
  • swelling of the face, lips, mouth, tongue, or throat; hives and breathing difficulties; sudden drop in blood pressure. The frequency of severe allergic reactions is very rare (anaphylactic reactions, including anaphylactic shock, may occur in up to 1 in 10,000 people), and uncommon (angioedema and allergic edema may occur in 1 in 100 people).

General list of possible adverse effects:
Common (may occur in up to 1 in 10 patients)

• reduction in red blood cells, which may cause pale skin and lead to weakness or shortness of breath,
• bleeding from the stomach or intestines, bleeding from the urinary or genital tract (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding from gums,
• bleeding into the eye (including bleeding from the sclera),
• bleeding into tissues or body cavities (hematoma, bruising),
• presence of blood in sputum (hemoptysis) when coughing,
• bleeding from or under the skin,
• bleeding after surgery,
• oozing of blood or fluid from a surgical wound,
• swelling of limbs,
• limb pain,
• kidney function disorders (may be observed in tests performed by a doctor),
• fever,
• stomach pain, indigestion, nausea or vomiting, constipation, diarrhea,
• low blood pressure (symptoms may include dizziness or fainting upon standing),
• general loss of strength and energy (weakness, fatigue), headache, dizziness,
• rash, itching of the skin,
• increased activity of certain liver enzymes, which may be seen in blood test results.

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

• bleeding into the brain or within the skull (see signs of bleeding above),
• bleeding into a joint causing pain and swelling,
• thrombocytopenia (low platelet count, the blood cells involved in blood clotting),
• allergic reactions, including allergic skin reactions,
• liver function disorders (may be observed in tests performed by a doctor),
• blood tests may show increased levels of bilirubin, increased activity of certain pancreatic or liver enzymes, or increased platelet count,
• fainting,
• malaise,
• rapid heartbeat,
• dry mouth,
• urticaria (hives).

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

• bleeding into muscles,
• cholestasis (bile stasis), hepatitis including liver cell damage,
• yellowing of the skin and eyes (jaundice),
• localized swelling,
• blood collection (hematoma) in the groin as a complication of cardiac catheterization when a catheter is inserted into an artery in the leg (pseudoaneurysm).

Very rare (may occur in up to 1 in 10,000 patients)

• accumulation of eosinophils, a type of white granulocytic blood cells, causing lung inflammation (eosinophilic pneumonia).

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

• kidney failure following severe bleeding,
• bleeding in the kidneys, sometimes with blood in urine, leading to impaired kidney function (drug-induced nephropathy associated with anticoagulant medicines),
• increased pressure in the muscles of arms and legs following bleeding, which may lead to pain, swelling, altered sensation, numbness, or paralysis (compartment syndrome after bleeding).

Reporting of adverse effects
If any adverse effects occur, including any not listed
in this leaflet, you should 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 to provide more information on the safety of the medicine.

5. How to store Mibrex

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the stated month.
The label on the packaging shows the expiry date after the abbreviation EXP, and the batch number after the abbreviation Lot/LOT.
No special storage precautions are required.
Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Mibrex contains

• The active substance is rivaroxaban. Each coated tablet contains 2.5 mg of rivaroxaban.
• The other ingredients are: tablet core: sodium lauryl sulfate, monohydrate lactose, microcrystalline cellulose, sodium croscarmellose, hypromellose, magnesium stearate.
  tablet coating (Opadry Yellow 03F12967): hypromellose, titanium dioxide (E 171), talc, polyethylene glycol 8000, yellow iron oxide (E 172).

What Mibrex looks like and contents of the pack
Mibrex 2.5 mg are light yellow, round, biconvex, film-coated tablets with the number "2.5" embossed on one side.
The tablets are contained in transparent blisters made of Aluminium/PVC/PVDC foil, packed into cardboard boxes containing 14, 20, 28, 30, 56, 60, 98, 168 or 196 film-coated tablets, or in single-dose perforated blisters made of Aluminium/PVC/PVDC foil, packed into cardboard boxes containing 10 x 1 tablet or 100 x 1 tablet, or in multipacks containing 10 boxes, each with 10 x 1 film-coated tablet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
tel. + 48 22 364 61 01