Mibrex

Package Leaflet: Information for the Patient

Mibrex, 15 mg, film-coated tablets

Mibrex, 20 mg, film-coated tablets

Rivaroxaban

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Mibrex and what is it 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 is Mibrex and what is it used for

Mibrex contains the active substance rivaroxaban.
Mibrex is used in adults 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 heartbeat called atrial fibrillation not caused by a heart valve problem;
• treat blood clots in the veins of the legs (deep vein thrombosis) and blood vessels in the lungs (pulmonary embolism) and prevent the recurrence of blood clots in the blood vessels of the legs and/or lungs. Mibrex is used in children and adolescents under 18 years of age and weighing 30 kg or more to:
• treat and prevent the recurrence of blood clots in the veins or blood vessels in the lungs, after at least 5 days of initial treatment with injectable medicines used to treat blood clots.

Mibrex belongs to a group of medicines called anticoagulants. Its action is based on
blocking the blood clotting factor (factor Xa) and thereby reducing the tendency to form
blood clots.

2. Important information before taking Mibrex

When not to take 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 the body that leads to an increased risk of serious bleeding (e.g. stomach ulcer, injury or bleeding into the brain, recent brain or eye surgery),

or recent bleeding into the brain or eye.

• if the patient is taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when changing anticoagulant treatment or when heparin is given to maintain the patency of a vein or artery catheter,
• if the patient has liver disease that leads to an increased risk of bleeding,
• if the patient is pregnant or breastfeeding. Do not take Mibrex and inform your doctorif you suspect that you have any of the above conditions.

Warnings and precautions

Before starting to take Mibrex, discuss it with your doctor or pharmacist.

Be particularly careful when taking Mibrex:

• if the patient has an increased risk of bleeding, such as:
• severe kidney disease in adults and moderate or severe kidney disease in children and adolescents, as kidney function may affect the amount of medicine that works in the patient's body,
• taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin) when changing anticoagulant treatment or when heparin is given to maintain the patency of a vein or artery catheter (see "Mibrex and other medicines"),
• bleeding disorders,
• very high blood pressure that does not decrease despite taking medicines,
• stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestines and stomach or inflammation of the esophagus (throat and esophagus) e.g. due to reflux disease of the esophagus (backflow of stomach acid into the esophagus) or tumors located in the stomach or intestines or genital or urinary system,
• eye blood vessel disease (retinopathy),
• pulmonary disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding,
• in patients with artificial heart valves,
• if the patient has a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), the patient should inform the doctor, who will decide on possible changes in treatment,
• if the patient has been diagnosed with abnormal blood pressure or is scheduled for surgery or other treatment to remove a blood clot from the lungs.

If you suspect that you have any of the above conditions, inform

your doctorbefore taking Mibrex. The doctor will decide whether to use this medicine and whether
the patient should be subject to particularly close monitoring.

If you need to have surgery:

• follow your doctor's instructions carefully regarding the intake of Mibrex at a precisely specified time before and after surgery,
• if catheterization or spinal puncture is planned during surgery (e.g. for epidural or spinal anesthesia or pain relief):
• it is very important to take Mibrex before and after the puncture or catheter removal, according to the doctor's instructions
• due to the need for special caution, you should immediately inform your doctor if you experience numbness or weakness of the legs, bowel or bladder disorders after the anesthesia is completed.

Children and adolescents

Mibrex tablets are not recommended for children with a body weight below 30 kg. There is a lack of sufficient data on the use of Mibrex in children and adolescents for indications in adults.

Mibrex and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription.

• If you are taking certain medicines for fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are used only locally on the skin, ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol), certain medicines for bacterial infections (e.g. clarithromycin, erythromycin), certain antiviral medicines for HIV infection or AIDS treatment (e.g. ritonavir), other medicines that reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists, such as warfarin or acenocoumarol), anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid), dronedarone, a medicine used to treat heart rhythm disorders, certain medicines for depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs)).

If you suspect that you have any of the above conditions, inform

your doctorbefore taking Mibrex, as the effect of Mibrex may be enhanced.
The doctor will decide whether to use this medicine and whether the patient should be subject to particularly close monitoring.
If the doctor considers that the patient is at increased risk of developing stomach or intestinal ulcers, he/she may use preventive treatment.

• If you are taking certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital), St. John's wort ( Hypericum perforatum), a herbal medicine used for depression, rifampicin, which belongs to a group of antibiotics.

If you suspect that you have any of the above conditions, inform

your doctorbefore taking Mibrex, as the effect of Mibrex may be reduced. The doctor will decide whether to use Mibrex and whether the patient should be subject to particularly close monitoring.

Pregnancy and breastfeeding

Do not take Mibrex if you are pregnant or breastfeeding. If there is a risk that you may become pregnant, use effective contraception while taking Mibrex. If you become pregnant while taking this medicine, inform your doctor immediately, who will decide on further treatment.

Driving and using machines

Mibrex may cause dizziness (frequent side effects) or fainting (uncommon side effects) (see section 4. "Possible side effects"). Patients who experience these side effects should not drive, ride a bicycle, or operate tools or machines.

Mibrex contains lactose and sodium

If you have previously been diagnosed with intolerance to some sugars, you should contact your doctor before taking the medicine.
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means the product is considered "sodium-free".

3. How to take Mibrex

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Mibrex should be taken with food.
Swallow the tablet(s) whole, preferably with water.
If you have difficulty swallowing whole tablets, talk to your doctor about other ways to take Mibrex. The tablet can be crushed and mixed with water or apple sauce, just before taking it. After such a mixture, eat a meal immediately.
If necessary, your doctor may also give you a crushed Mibrex tablet through a gastric tube.

How many tablets to take

• Adults
• In preventing the formation of blood clots in the brain (stroke) and other blood vessels in the body: The recommended dose is one Mibrex 20 mg tablet once a day. If the patient has kidney disease, the dose may be reduced to one Mibrex 15 mg tablet once a day.

If the patient needs a procedure to clear the blood vessels in the heart (called percutaneous coronary intervention - PCI with stent placement), there is limited evidence for a dose reduction to one Mibrex 15 mg tablet once a day (or one Mibrex 10 mg tablet once a day in case of kidney function disorder) in combination with an antiplatelet medicine such as clopidogrel.

• In treating blood clots in the veins of the legs, blood clots in the blood vessels of the lungs, and preventing the recurrence of blood clots: The recommended dose is one Mibrex 15 mg tablet twice a day for the first 3 weeks. For treatment after 3 weeks, the recommended dose is one Mibrex 20 mg tablet once a day. After at least 6 months of treatment for blood clots, the doctor may decide to continue treatment with one 10 mg tablet once a day or one 20 mg tablet once a day. If the patient has kidney disease and is taking one Mibrex 20 mg tablet once a day, the doctor may decide to reduce the dose after 3 weeks of treatment to one Mibrex 15 mg tablet once a day, if the risk of bleeding is greater than the risk of further blood clots.
• Children and adolescentsThe dose of Mibrex depends on body weight and will be calculated by the doctor. o The recommended dose for children and adolescents with a body weight of 30 kg to less than 50 kgis one Mibrex 15 mgtablet once a day. o The recommended dose for children and adolescents with a body weight of 50 kgor more is one Mibrex 20 mgtablet once a day.

Each Mibrex dose should be taken with food, with a drink (e.g. water or juice).
Tablets should be taken every day at about the same time. It's a good idea to set an alarm to remind you.
For parents or caregivers: observe the child to make sure they have taken the whole dose.
The dose of Mibrex is dependent on body weight, so it's essential to come to scheduled doctor's appointments, as the dose may need to be adjusted due to weight changes.
Never adjust the dose yourself.If necessary, the doctor will adjust the dose.
Do not divide the tablet to get a partial dose. If a smaller dose is needed, use other medicines in the form of granules for oral suspension.
For children and adolescents who are unable to swallow whole tablets, use other medicines in the form of granules for oral suspension.
If an oral suspension is not available, you can crush the Mibrex tablet and mix it with water or apple sauce, just before taking it. After such a mixture, eat a meal immediately.
If necessary, the doctor may also give you a crushed Mibrex tablet through a gastric tube.

In case of spitting out the dose or vomiting

• less than 30 minutes after taking Mibrex, take a new dose.
• more than 30 minutes after taking Mibrex, do nottake a new dose. In this case, take the next dose of Mibrex at the usual time.

Contact your doctor if you spit out the dose or vomit repeatedly after taking Mibrex.

When to take Mibrex

Take the tablet(s) every day until your doctor decides to stop the treatment.
It's best to take the tablet(s) at the same time every day, as it's easier to remember.
Your doctor will decide how long to continue the treatment.
Preventing the formation of blood clots in the brain (stroke) and other blood vessels in the body:
If your heart rhythm needs to be restored to normal using a procedure called cardioversion, take Mibrex as directed by your doctor.

Missing a dose of Mibrex

• Adults, children, and adolescents: If you are taking one 20 mg or one 15 mg tablet once a day and you miss a dose, take it as soon as possible. Do not take more than one tablet in a 24-hour period to make up for the missed dose. Take the next tablet at the usual time the next day, and then take one tablet once a day.
• Adults: If you are taking one 15 mg tablet twice a day and you miss a dose, take it as soon as possible. Do not take more than two 15 mg tablets in a 24-hour period. If you miss a dose, you can take two 15 mg tablets at the same time to get a total of two tablets (30 mg) in a 24-hour period. The next day, continue taking one 15 mg tablet twice a day.

Taking more Mibrex than prescribed

If you have taken more Mibrex than prescribed, contact your doctor immediately. Taking too much Mibrex increases the risk of bleeding.

Stopping Mibrex treatment

Do not stop taking Mibrex without consulting your doctor first, as Mibrex prevents a serious condition.
If you have any further questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, Mibrex can cause side effects, although not everybody gets them.
Like other medicines that reduce blood clotting, Mibrex can cause bleeding, which can be life-threatening. Excessive bleeding can lead to a sudden drop in blood pressure (shock). These may not always be obvious or visible signs of bleeding.
Tell your doctor immediatelyif you experience any of the following side effects:

• Signs of bleeding:
• bleeding into the brain or inside the skull (symptoms may include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and stiffness of the neck. This is a serious medical emergency. Seek medical help immediately!),
• prolonged or excessive bleeding,
• unusual weakness, fatigue, pallor, dizziness, headache, unexplained swelling, shortness of breath, chest pain, or angina. The doctor may decide to monitor the patient closely or change the treatment.
• Signs of severe skin reactions:
• widespread, acute skin rash, blistering, or changes in the mucous membranes, e.g. on the tongue or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• a drug reaction that causes a rash, fever, inflammation of internal organs, blood disorders, and systemic disorders (DRESS syndrome). The frequency of these side effects is very rare (less than 1 in 10,000 people).
• Signs of severe allergic reactions
• swelling of the face, lips, mouth, tongue, or throat; hives, and difficulty breathing; sudden drop in blood pressure. The frequency of severe allergic reactions is very rare (anaphylactic reactions, including anaphylactic shock, may occur in less than 1 in 10,000 people) and uncommon (angioedema and allergic edema may occur in 1 in 100 people).

General list of possible side effects in adults, children, and adolescents:

Common(may affect up to 1 in 10 people)

• reduced red blood cell count, which can cause pallor and be the cause of weakness or shortness of breath,
• bleeding from the stomach or intestines, bleeding from the urinary tract (including blood in the urine and heavy menstrual bleeding), nosebleeds, bleeding from the gums,
• bleeding into the eye (including bleeding from the conjunctiva),
• bleeding into tissues or body cavities (hematoma, bruising),
• presence of blood in sputum (hemoptysis) when coughing,
• bleeding from the skin or subcutaneous bleeding,
• bleeding after surgery,
• oozing of blood or fluid from the wound after surgery,
• swelling of the limbs,
• limb pain,
• kidney function disorders (can be observed in tests performed by the doctor),
• fever,
• stomach pain, nausea, feeling sick (nausea) or vomiting, constipation, diarrhea,
• low blood pressure (symptoms may include dizziness or fainting when standing),
• general weakness and lack of energy (weakness, fatigue), headache, dizziness,
• rash, itching of the skin,
• increased activity of certain liver enzymes, which can be seen in blood test results.

Uncommon(may affect up to 1 in 100 people)

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

Rare(may affect up to 1 in 1,000 people)

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

Very rare(may affect up to 1 in 10,000 people)

• accumulation of eosinophils, a type of white granular blood cells, which can cause inflammation in the lungs (eosinophilic pneumonia).

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

• kidney failure after severe bleeding,
• bleeding in the kidneys, sometimes with blood in the urine, leading to kidney failure (nephropathy associated with anticoagulant therapy),
• increased pressure in the muscles of the legs and arms, occurring after bleeding, which can lead to pain, swelling, changes in sensation, numbness, or paralysis (compartment syndrome after bleeding).

Side effects in children and adolescents

Generally, the side effects observed in children and adolescents treated with rivaroxaban were similar in type to those observed in adults and were mainly mild to moderate.
Side effects observed more frequently in children and adolescents:
Very common(may affect more than 1 in 10 people)

• headache,
• fever,
• nosebleeds, vomiting.

Common(may affect up to 1 in 10 people)

• rapid heartbeat,
• blood test results may show increased bilirubin levels (a bile pigment),
• thrombocytopenia (low platelet count, cells involved in blood clotting),
• excessive menstrual bleeding.

Uncommon(may affect up to 1 in 100 people)

• blood test results may show increased levels of a bilirubin subtype (direct bilirubin, a bile pigment).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Monitoring 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
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this 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 month.
The inscription on the packaging after the abbreviation EXP means the expiry date, and after the abbreviation Lot/LOT means the batch number.
There are no special precautions for storing the medicine.
Crushed tablets
Crushed tablets are stable in water or apple sauce for up to 4 hours.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Mibrex contains

• The active substance of Mibrex is rivaroxaban. Each film-coated tablet contains 15 mg or 20 mg of rivaroxaban.
• The other ingredients are: tablet core: sodium lauryl sulfate, lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose, type 2910 (5 mPas), magnesium stearate; 15 mg tablet coating (Opadry II Pink 33G240024 ) : hypromellose, type 2910 (6 mPas), titanium dioxide (E 171), lactose monohydrate, macrogol 3350, triacetin, iron oxide red (E 172), iron oxide black (E 172); 20 mg tablet coating ( Opadry II Red 33G250007 ) : hypromellose type 2910 (6 mPAS), titanium dioxide (E 171), lactose monohydrate, macrogol 3350, triacetin, iron oxide red (E 172), iron oxide yellow (E 172).

What Mibrex looks like and contents of the pack

Mibrex, 15 mg are pink, round, biconvex film-coated tablets, with the number "15" embossed on one side.
The tablets are in transparent blisters, packaged in cardboard boxes, containing 10, 14, 28, 42, 98, or 100 film-coated tablets or in single-dose perforated blisters (Aluminium /PVC/PVDC), packaged in cardboard boxes containing 10 x 1 tablet or 100 x 1 tablet or in collective packaging containing 10 boxes, each with 10 x 1 film-coated tablet.
Mibrex, 20 mg are reddish-brown, round, biconvex film-coated tablets, with the number "20" embossed on one side.
The tablets are in transparent blisters, packaged in cardboard boxes, containing 10, 14, 28, 30, 56, 60, or 98 film-coated tablets or in single-dose perforated blisters (Aluminium /PVC/PVDC), packaged in cardboard boxes containing 10 x 1 tablet or 100 x 1 tablet or in collective packaging containing 10 boxes, each with 10 x 1 film-coated tablet.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Polpharma S.A.
Pelplińska 19
83-200 Starogard Gdański
phone: +48 22 364 61 01
Date of last revision of the leaflet:November 2023