Mibrex

Package Leaflet: Information for the User

Mibrex, 15 mg hard capsules

Mibrex, 20 mg hard capsules

Rivaroxaban

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

• Keep this leaflet, as you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their 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 with a body weight of 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 anti-coagulant medicines.

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 an organ that increases the risk of serious bleeding (e.g., stomach ulcer, injury or bleeding in the brain, recent brain or eye surgery),

or recent surgery.

• if the patient is taking other medicines that prevent the formation of blood clots (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 increases the risk of bleeding,
• if the patient is pregnant or breastfeeding.

Do not take Mibrex, and inform your doctor if you suspect that you have any of the above conditions.

Warnings and precautions

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

When to 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 the formation of blood clots (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 treatment,
• 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,
• disease of the blood vessels in the back of the eye (retinopathy),
• pulmonary disease in which the airways are dilated and filled with pus (bronchiectasis) or previous bleeding from the lungs,
• 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 their doctor, who will decide whether to change the treatment,
• if the patient has unstable blood pressure or is scheduled for surgery or other treatment to remove a blood clot from the lungs.

If the patient suspects that they have any of the above conditions, they should inform their doctor

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

If the patient needs to undergo surgery:

• it is very important to follow the doctor's instructions regarding the intake of Mibrex at a precisely specified time before or after surgery,
• if a lumbar puncture or spinal catheter insertion is planned during surgery (e.g., for spinal or epidural anesthesia or to reduce pain):
• it is very important to take Mibrex before and after the puncture or catheter removal, as instructed by the doctor,
• due to the need for particular caution, the doctor should be informed immediately if numbness or weakness of the legs, bowel or bladder disorders occur after the anesthesia is completed.

Children and adolescents

Mibrex 15 mg capsules are not recommended for children with a body weight below 30 kg.
Mibrex 20 mg capsules are not recommended for children with a body weight below 50 kg.
There is a lack of sufficient data on the use of rivaroxaban 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 that are available 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,
• ketokonazole 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 used to treat HIV or AIDS (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 used to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs)).

If the patient suspects that they have any of the above conditions, they should inform

their doctorbefore taking Mibrex, as the effect of Mibrex may be increased. The doctor will decide whether to use this medicine and whether the patient should be subject to particularly close monitoring.
If the doctor believes that the patient is at increased risk of developing stomach or duodenal ulcers, they may use a treatment to prevent ulcers.

• 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 the patient suspects that they have any of the above conditions, they should inform

their 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, you should use effective contraception while taking Mibrex. If you become pregnant while taking Mibrex, you should inform your doctor immediately, who will decide on further treatment.

Driving and using machines

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

Mibrex contains lactose monohydrate (a type of sugar) and sodium

If you have been diagnosed with an intolerance to some sugars, you should contact your doctor before taking Mibrex.
The medicine contains less than 1 mmol (23 mg) of sodium per capsule, so it 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 capsule(s) whole, preferably with water.
If you have difficulty swallowing the whole capsule, talk to your doctor about other ways to take Mibrex. The contents of the capsule can be mixed with water or apple sauce, immediately before taking it. After taking this mixture, eat a meal.
If necessary, your doctor may also give you the contents of the Mibrex capsule through a gastric tube.

How many capsules to take

Adults

• To prevent blood clots in the brain (stroke) and other blood vesselsThe recommended dose is one Mibrex 20 mg capsule once a day. If you have kidney problems, the dose may be reduced to one Mibrex 15 mg capsule once a day.

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

• To treat blood clots in the veins of the legs, blood clots in the lungs, and to prevent the recurrence of blood clotsThe recommended dose is one Mibrex 15 mg capsule twice a day for the first 3 weeks. For treatment after 3 weeks, the recommended dose is one Mibrex 20 mg capsule once a day. After at least 6 months of treatment for blood clots, your doctor may decide to continue treatment with one 10 mg capsule once a day or one 20 mg capsule once a day. If you have kidney function disorders and are taking one Mibrex 20 mg capsule once a day, your doctor may decide to reduce the dose after 3 weeks of treatment to one Mibrex 15 mg capsule once a day, if the risk of bleeding is greater than the risk of further blood clots.

Children and adolescents

The dose of Mibrex depends on body weight and will be calculated by your doctor.

• For children and adolescents with a body weight from 30 kg to less than 50 kgThe recommended dose is one Mibrex 15 mg capsule once a day.
• For children and adolescents with a body weight of 50 kg or moreThe recommended dose is one Mibrex 20 mg capsule once a day.

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

If a dose is spat out or vomited

• 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 or vomit a dose of Mibrex repeatedly.

When to take Mibrex

Take the capsule(s) every day until your doctor decides to stop the treatment.
It is best to take the capsule(s) at the same time every day, as it will be easier to remember.
Your doctor will decide how long you should continue the treatment.
To prevent 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 instructed by your doctor.

Taking more Mibrex than prescribed

If you have taken too many Mibrex capsules, contact your doctor immediately.
Taking too much Mibrex increases the risk of bleeding.

Missing a dose of Mibrex

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

Stopping treatment with Mibrex

Do not stop taking Mibrex without first talking to your doctor, as Mibrex treats and prevents serious diseases.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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 may cause bleeding, which can be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). These signs of bleeding may not always be obvious or visible.

Immediately inform your doctor if you or your child 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. Your doctor may decide to monitor you closely or change your treatment.
• Signs of severe skin reactions:
• widespread, severe skin rash, blistering, or skin peeling (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 patients).
• Signs of severe allergic reactions:
• swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing; hives and difficulty breathing; sudden drop in blood pressure. The frequency of severe allergic reactions is very rare (anaphylactic reactions, including anaphylactic shock, occur in less than 1 in 10,000 patients) and uncommon (angioedema and allergic edema occur in less than 1 in 100 patients).

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

Common side effects(occur in less than 1 in 10 patients)

• reduced red blood cell count, which may cause pallor and be the cause of weakness or shortness of breath,
• bleeding from the stomach or intestine, bleeding from the urinary or reproductive system (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 when coughing,
• bleeding from the skin or subcutaneous bleeding,
• bleeding after surgery,
• oozing of blood or fluid from a wound after surgery,
• swelling of the limbs,
• limb pain,
• kidney function disorders (which can be observed in tests performed by your doctor),
• fever,
• stomach pain, nausea, vomiting, constipation, diarrhea,
• low blood pressure (symptoms may include dizziness or fainting when standing up),
• general weakness and lack of energy (weakness, fatigue), headache, dizziness,
• rash, itching,
• increased activity of certain liver enzymes, which can be seen in blood test results.

Uncommon side effects(occur in less than 1 in 100 patients)

• bleeding into the brain or inside the skull (see above signs of bleeding),
• bleeding into a joint, causing pain and swelling,
• thrombocytopenia (low platelet count, cells involved in blood clotting),
• allergic reactions, including allergic skin reactions,
• liver function disorders (which can be observed in tests performed by your 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 side effects(occur in less than 1 in 1,000 patients)

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

Very rare side effects(occur in less than 1 in 10,000 patients)

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

Side effects with unknown frequency(cannot be estimated from 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 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 Mibrex were similar in type to those observed in adults and were mostly mild to moderate.
Side effects observed more frequently in children and adolescents:
Very common side effects(occur in more than 1 in 10 patients)

• headache,
• fever,
• nosebleeds,
• vomiting.

Common side effects(occur in less than 1 in 10 patients)

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

Uncommon side effects(occur in less than 1 in 100 patients)

• blood test results may show increased direct bilirubin levels.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety 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 blister and carton after EXP. The expiry date refers to the last day of the month.
PVC/PVDC/Aluminum blisters: Store in a temperature below 30°C. Store in the original package to protect from moisture.
Aluminum/OPA/Aluminum/PVC blisters: No special storage precautions are required.
Medicines should not be disposed of via wastewater or household waste. 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 Mibrex contains

• The active substance is rivaroxaban. Each hard capsule contains 15 mg or 20 mg of rivaroxaban.
• The other ingredients are: Capsule contents: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose, sodium lauryl sulfate, magnesium stearate.

Capsule shell: gelatin, titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172), and iron oxide black (E 172).

What Mibrex looks like and contents of the pack

Mibrex 15 mg hard capsules are white or almost white powder, in a size 1 (approximately 19 mm long) capsule with a light brown opaque cap and body.
Mibrex 20 mg hard capsules are white or almost white powder, in a size 0 (approximately 22 mm long) capsule with a dark brown opaque cap and body.
The hard capsules are in PVC/PVDC/Aluminum or Aluminum/OPA/Aluminum/PVC blisters, in a carton.
Mibrex 15 mg is available in packs of 14, 28, 30, 42, 84, 98, and 100 hard capsules.
Mibrex 20 mg is available in packs of 14, 28, 30, 84, 98, and 100 hard capsules.
Not all pack sizes may be marketed.

Marketing authorization holder and importer

Marketing authorization holder

Polpharma S.A.
Pelplińska 19, 83-200 Starogard Gdański
Phone: +48 22 364 61 01

Importer

Zentiva SA
B-dul Theodor Pallady nr. 50, sector 3
032266 Bucharest
Romania
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
Paola, PLA3000
Malta
Date of last revision of the leaflet:February 2024