Mibrex

Package leaflet: Information for the user

Mibrex, 15 mg hard capsules
Mibrex, 20 mg hard capsules
Rivaroxaban
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. 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 any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Mibrex is and what it is used for
2. What you need to know 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

Mibrex contains the active substance rivaroxaban. Mibrex is used in adults to:

• prevent blood clots in the brain (stroke) and in other blood vessels in the body in patients with a type of irregular heartbeat called non-valvular atrial fibrillation.
• treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and to prevent recurrence of blood clots in the veins 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 blood clots and prevent recurrence of blood clots in the veins or in the blood vessels of 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. It works by blocking a blood clotting factor (Factor Xa), 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 is experiencing excessive bleeding,
• if the patient has a disease or organ condition leading to an increased risk of serious bleeding (e.g. stomach ulcer, trauma or bleeding into the brain, recent surgery on the brain or eyes),
• if the patient is taking other medicines that prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin), except when switching anticoagulant therapy or if heparin is administered to maintain the patency of an intravenous or arterial catheter,
• if the patient has a liver disease that leads to an increased risk of bleeding,
• if the patient is pregnant or breastfeeding.

Mibrex must not be used, and the patient should inform the doctor if they suspect that any of the above circumstances apply.

Warnings and precautions

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

When to exercise particular caution when taking Mibrex

• if the patient has an increased risk of bleeding, such as in the following conditions:
  • severe kidney disease in adults, or moderate to severe kidney disease in children and adolescents, as kidney function may affect the amount of medicine acting in the patient's body,
  • taking other medicines that prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is administered to maintain the patency of an intravenous or arterial catheter (see section "Mibrex with other medicines"),
  • blood clotting disorders,
  • very high blood pressure that does not decrease despite taking medication,
  • diseases of the stomach or intestines that may cause bleeding, e.g. inflammation of the intestines and stomach or inflammation of the oesophagus (throat and oesophagus), e.g. due to gastro-oesophageal reflux disease (backflow of stomach acid into the oesophagus), or tumours located in the stomach or intestines or in the genital or urinary system,
  • blood vessel disease of the back of the eyeball (retinopathy),
  • lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding,
• in patients with prosthetic heart valves,
• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing an increased risk of blood clots), the patient should inform the doctor, who will decide whether a change in treatment is necessary,
• if the patient has been diagnosed with unstable blood pressure or is scheduled for surgery or other treatment aimed at removing a blood clot from the lungs.

If the patient suspects that any of the above conditions apply, they should inform the doctor
before taking Mibrex. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.

If the patient needs to undergo surgery:

• it is essential to strictly follow the doctor's instructions regarding the timing of taking Mibrex before or after surgery,
• if lumbar puncture or placement of a spinal catheter (e.g. for epidural or spinal anaesthesia or for pain relief) is planned during surgery:
  • it is very important to take Mibrex before and after the puncture or catheter removal exactly as directed by the doctor,
  • due to the need for special caution, the patient must immediately inform the doctor if numbness or weakness in the legs, or disturbances in bowel or bladder function occur after the anaesthesia ends.

Children and adolescents

Mibrex 15 mg capsules are not recommended for children weighing less than 30 kg.
Mibrex 20 mg capsules are not recommended for children weighing less than 50 kg.
There is insufficient data on the use of rivaroxaban in children and adolescents for the indications approved in adults.

Mibrex with other medicines

Inform your doctor or pharmacist about all medicines you are currently taking, have recently taken or plan to take, 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, a condition in which the body produces too much cortisol),
  • certain antibiotics (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),
  • 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 (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)).

If the patient suspects that any of the above conditions apply, they should inform the doctor
before taking 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 gastric or duodenal ulcer, they may prescribe treatment to prevent peptic ulcer disease.

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

If the patient suspects that any of the above conditions apply, they should inform the doctor
before taking 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 take 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 Mibrex, they should inform the doctor immediately, who will decide on further treatment.

Driving and operating machinery

Mibrex may cause dizziness (common side effects) and 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 monohydrate (a type of sugar) and sodium

If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.

The medicine contains less than 1 mmol (23 mg) of sodium per capsule; therefore, the medicine is considered "sodium-free".

3. How to take Mibrex

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult
your doctor or pharmacist.
Mibrex should be taken with food.
The capsule(s) should be swallowed whole, preferably with water.
If the patient has difficulty swallowing the entire capsule, they should discuss alternative
methods of taking Mibrex with their doctor. The contents of the capsule may be mixed with water or
apple puree immediately before administration. After taking this mixture, a meal should be
consumed promptly.
If necessary, a doctor may administer the emptied contents of the Mibrex capsule via a gastric
tube.

How many capsules to take

o Adults

• For prevention of blood clots in the brain (stroke) and other blood vessels in the body
  The recommended dose is one 20 mg Mibrex capsule once daily. If the patient has kidney problems, the dose may be reduced to one 15 mg Mibrex capsule once daily.

If the patient requires a procedure to open blocked blood vessels in the heart (called percutaneous coronary intervention – PCI with stent placement), there is limited evidence supporting dose reduction to one 15 mg Mibrex capsule once daily (or one 10 mg Mibrex capsule once daily in case of renal impairment), in combination with an antiplatelet medicine such as clopidogrel.

• For treatment of blood clots in the leg veins, blood clots in the blood vessels of the lungs, and prevention of recurrence of blood clots
  The recommended dose is one 15 mg Mibrex capsule twice daily for the first 3 weeks. For treatment beyond 3 weeks, the recommended dose is one 20 mg Mibrex capsule once daily. After at least 6 months of treatment for blood clots, the doctor may decide to continue treatment with either one 10 mg capsule once daily or one 20 mg capsule once daily. If the patient has impaired kidney function and is taking one 20 mg Mibrex capsule once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one 15 mg Mibrex capsule once daily, if the risk of bleeding is greater than the risk of further blood clots.

o Children and adolescents
The dose of Mibrex depends on body weight and will be calculated by the doctor.

• The recommended dose for children and adolescents with a body weight of 30 kg to below 50 kg is one 15 mg Mibrex capsule once daily.
• The recommended dose for children and adolescents with a body weight of 50 kg or more is one 20 mg Mibrex capsule once daily.

Each dose of Mibrex should be taken with a meal, accompanied by a drink (e.g. water or juice).
Capsules should be taken daily at approximately the same time. Consider setting an alarm as a reminder.
For parents or caregivers: observe the child to ensure they have taken the full dose.
The dose of Mibrex depends on body weight, so it is important to attend scheduled doctor appointments, as dose adjustments may be needed due to changes in weight.
Never adjust the dose independently. If necessary, the doctor will adjust the dose.
Do not split the capsule contents to achieve a partial dose. If a lower dose is required, an alternative medicine containing rivaroxaban in the form of granules for oral suspension should be used.
For children and adolescents who are unable to swallow the entire capsule, a medicine containing rivaroxaban in the form of granules for oral suspension should be used.
If the oral suspension is not available, the contents of the Mibrex capsule may be emptied and mixed with water or apple puree immediately before administration. After taking this mixture, a meal should be consumed. If necessary, a doctor may also administer the emptied capsule contents via a gastric tube.

If a dose is vomited or spit out

• Within 30 minutes of taking Mibrex, take a new dose.
• More than 30 minutes after taking Mibrex, do not take a new dose. In this case, take the next dose of Mibrex at the usual time.

Contact your doctor if repeated vomiting or spitting out of the dose occurs after taking Mibrex.

When to take Mibrex
The capsule(s) should be taken every day until the doctor decides to stop treatment.
It is best to take the capsule(s) at the same time each day, as this makes it easier to remember.
The doctor will decide how long the patient should continue treatment.
Prevention of blood clots in the brain (stroke) and other blood vessels in the body:
If a procedure called cardioversion is required to restore normal heart rhythm, Mibrex should be taken as directed by the doctor.

Taking more than the recommended dose of Mibrex
If the patient has taken too many Mibrex capsules, contact a doctor immediately.
Taking too high a dose of Mibrex increases the risk of bleeding.

Missing a dose of Mibrex

• Adults, children and adolescents: If the patient takes one 20 mg capsule or one 15 mg capsule once daily and a dose is missed, take the capsule as soon as possible. Do not take more than one capsule in a single day to make up for the missed dose. Take the next capsule the following day, then continue taking one capsule once daily.
• Adults: If the patient takes one 15 mg capsule twice daily and a dose is missed, take the capsule as soon as possible. Do not take more than two 15 mg capsules in a single day. If the patient forgot to take a dose, they may take two 15 mg capsules at the same time to achieve a total of two capsules (30 mg) taken within one day. The next day, continue taking one 15 mg capsule twice daily.

Stopping treatment with Mibrex
Do not stop taking Mibrex without first consulting your doctor, as Mibrex treats and prevents serious conditions.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicinal product may cause adverse reactions, although not everyone experiences them.
Like other medicines with a similar mechanism of action that reduce blood clot formation, Mibrex may cause bleeding, which potentially could be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). Signs of bleeding are not always obvious or visible.
Immediately inform a doctor if any of the following adverse reactions occur in an adult or child:

• Signs of bleeding:
  • bleeding into the brain or inside the skull (symptoms may include headache, one-sided paralysis, vomiting, seizures, decreased level of consciousness, and neck stiffness. This is a serious medical emergency. Seek immediate medical assistance!),
  • prolonged or excessive bleeding,
  • unusual weakness, fatigue, pallor, dizziness, headache, unexplained swelling, shortness of breath, chest pain, or angina. The physician may decide that close monitoring of the patient or a change in treatment approach is necessary.
• Signs of severe skin reactions:
  • widespread, acute skin rash, blistering, or mucosal lesions, e.g., on the tongue 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 reactions is very rare (occurring in less than 1 in 10,000 patients).
• Signs of severe allergic reactions:
  • swelling of the face, lips, oral cavity, tongue, or throat, difficulty swallowing; urticaria and breathing difficulties; 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 adverse reactions in adults, children, and adolescents
Common adverse reactions (occur in less than 1 in 10 patients)

• decreased number of red blood cells, which may cause skin pallor and lead to weakness or shortness of breath,
• gastrointestinal or intestinal bleeding, bleeding from the urinary or genital tract (including blood in urine and severe menstrual bleeding), nosebleeds, gum bleeding,
• bleeding into the eye (including conjunctival hemorrhage),
• bleeding into tissues or body cavities (hematoma, bruising),
• presence of blood in sputum (hemoptysis) during coughing,
• skin bleeding or subcutaneous bleeding,
• postoperative bleeding,
• oozing of blood or fluid from surgical wound,
• limb swelling,
• limb pain,
• kidney function disorders (observable in physician-performed tests),
• 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,
• skin rash, itching,
• increased activity of certain liver enzymes, which may be observed in blood test results.

Uncommon adverse reactions (occur in less than 1 in 100 patients)

• intracranial or cerebral hemorrhage (see signs of bleeding above),
• bleeding into a joint causing pain and swelling,
• thrombocytopenia (low platelet count, blood cells involved in blood clotting),
• allergic reactions, including allergic skin reactions,
• liver function disorders (observable in physician-performed tests),
• blood tests may show increased bilirubin levels, increased activity of certain pancreatic or liver enzymes, or increased platelet count,
• fainting,
• malaise,
• rapid heartbeat,
• dry mouth,
• urticaria.

Rare adverse reactions (occur in less than 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 accumulation (hematoma) in the groin area as a complication of cardiac catheterization when the catheter is inserted into an artery in the leg (pseudoaneurysm).

Very rare adverse reactions (occur in less than 1 in 10,000 patients)

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

Adverse reactions with unknown frequency (cannot be estimated from available data)

• kidney failure following severe bleeding,
• bleeding in the kidneys, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-related nephropathy),
• increased pressure within the muscle compartments of arms or legs following bleeding, which may cause pain, swelling, altered sensation, numbness, or paralysis (compartment syndrome following bleeding).

Adverse reactions in children and adolescents
In general, adverse reactions observed in children and adolescents treated with Mibrex were similar in type to those seen in adults and were mostly mild to moderate in severity.
Adverse reactions observed more frequently in children and adolescents:
Very common adverse reactions (occur in more than 1 in 10 patients)

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

Common adverse reactions (occur in less than 1 in 10 patients)

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

Uncommon adverse reactions (occur in less than 1 in 100 patients)

• blood tests may show increased levels of a subcategory of bilirubin (direct bilirubin, a bile pigment).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions 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
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Mibrex

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the cardboard
package following EXP. The expiry date refers to the last day of the stated month.
PVC/PVDC/Aluminium blisters: Store below 30°C. Keep in the original packaging to protect
from moisture.
Aluminium/OPA/Aluminium/PVC blisters: No special storage instructions for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures will help protect the
environment.

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

Marketing Authorisation Holder and Importer
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. +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