Mibrex

Package leaflet: Information for the user

Mibrex 10 mg hard capsules
Rivaroxaban
Please read all of 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, 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 get 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 you take 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 and is used in adults to:

• prevent blood clots in the veins after hip or knee replacement surgery. Your doctor has prescribed this medicine because your risk of developing blood clots is higher after surgery.
• 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 the recurrence of blood clots in the blood vessels of the legs and/or lungs.

Mibrex belongs to a group of medicines called anticoagulants. It works by blocking a blood clotting factor (Factor Xa), thereby reducing the tendency for blood clots to form.

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 affecting an organ that increases the risk of serious bleeding (e.g. stomach ulcer, trauma or bleeding in the brain, recent surgery on the brain or eyes),
• 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 an intravenous or arterial catheter,
• if the patient has a liver disease that increases the risk of bleeding,
• if the patient is pregnant or breastfeeding. Mibrex must not be used, and the doctor must be informed if the patient suspects that any of the above conditions apply.

Warnings and precautions
Before starting Mibrex, discuss this with your doctor or pharmacist.
When to exercise special caution when using Mibrex

• if the patient has an increased risk of bleeding, such as in the following conditions:
  • moderate or severe kidney disease, 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 if 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 medication,
  • stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestine 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, intestines, genital or urinary system,
  • vascular disease of the posterior part of the eyeball (retinopathy),
  • lung disease with dilated bronchi 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 increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment needs to be changed,
• if the patient has been diagnosed with unstable blood pressure or if surgery or other treatment to remove a blood clot from the lungs is planned.

If the patient suspects any of the above conditions apply, the doctor must be informed
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 when to take Mibrex before or after surgery.
• if lumbar puncture or placement of a catheter into the spine is planned during surgery (e.g. for epidural or spinal anaesthesia or for pain relief):
  • it is very important to take Mibrex before and after the puncture or removal of the catheter as directed by the doctor,
  • due to the need for special caution, the doctor must be informed immediately if numbness or weakness in the legs, or bowel or bladder dysfunction occur after the anaesthesia wears off.

Children and adolescents
Mibrex 10 mg capsules are not recommended for patients under 18 years of age. There is insufficient data on the use of the medicine in children and adolescents.
Mibrex with other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently used, as well as any medicines the patient plans to take, including those available without a prescription.

• If the patient is taking
  • certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless 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 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 any of the above conditions apply, the doctor must be informed
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 the patient to be at increased risk of developing stomach or duodenal ulcers, preventive treatment for peptic ulcer disease 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,
  • rifampicin, an antibiotic.

If the patient suspects any of the above conditions apply, the doctor must be informed
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 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 must be used during treatment with Mibrex. If the patient becomes pregnant while taking this medicine, 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 10 mg contains lactose monohydrate (a type of sugar) and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking the medicine.
The medicine contains less than 1 mmol (23 mg) of sodium per capsule, meaning the medicine is considered "sodium-free".

3. How to take Mibrex

This medicine should always be taken as directed by the physician. If in doubt, consult
your doctor or pharmacist.
How many capsules to take

• To prevent the formation of blood clots in veins after hip or knee replacement surgery
  The recommended dose is one 10 mg Mibrex capsule taken once daily.
• For the treatment of blood clots in the leg veins, blood clots in the blood vessels of the lungs, and to prevent recurrence of blood clots
  After at least 6 months of treatment for blood clots, the recommended dose is one 10 mg capsule once daily or one 20 mg capsule once daily. The physician has prescribed the patient Mibrex 10 mg once daily.

The capsule should be swallowed whole, preferably with water.
Mibrex may be taken with or without food.
If the patient has difficulty swallowing the entire capsule, discuss with the doctor alternative
methods of taking Mibrex. The contents of the capsule may be mixed with water or apple puree immediately before administration.
If necessary, the physician may administer the emptied contents of the Mibrex capsule via a gastric tube.
When to take Mibrex
The capsule should be taken every day until the physician decides to discontinue treatment.
It is best to take the capsule at the same time each day, as this makes it easier to remember.
The physician will decide how long treatment should continue.
To prevent blood clots in the leg veins after hip or knee replacement surgery:
The first capsule should be taken 6 to 10 hours after surgery.
In patients undergoing major hip surgery, treatment usually lasts 5 weeks.
In patients undergoing major knee surgery, treatment usually lasts 2 weeks.
Taking more Mibrex than recommended
If the patient has taken more than the prescribed dose of Mibrex, contact the doctor immediately.
Taking too high a dose of Mibrex increases the risk of bleeding.
Missing a dose of Mibrex
If the patient forgets to take a dose, take the capsule as soon as remembered.
Take the next capsule the following day, then continue taking the capsules as usual, once daily.
Do not take a double dose to make up for a missed capsule.
Stopping Mibrex treatment
Do not stop taking Mibrex without first consulting your doctor, as Mibrex helps prevent a serious condition.
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 will experience 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). Bleeding may not always be obvious or visible.
You should immediately inform your doctor if any of the following adverse reactions occur:

• 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 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 lesions on mucous membranes, 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 reactions is very rare (up to 1 in 10,000 people).
• Signs of serious allergic reactions:
  • swelling of the face, lips, mouth, 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
Common adverse reactions (occur in less than 1 in 10 patients)

• decreased number of red blood cells, which may cause pale skin and lead to weakness or shortness of breath,
• gastrointestinal or intestinal bleeding, bleeding from the urinary or genital tract (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding gums,
• bleeding into the eye (including conjunctival hemorrhage),
• bleeding into tissues or body cavities (hematoma, bruising),
• presence of blood in sputum (hemoptysis) during coughing,
• bleeding from the skin or subcutaneous bleeding,
• postoperative bleeding,
• oozing of blood or fluid from a surgical wound,
• limb swelling,
• 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 observed in blood test results.

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

• bleeding into the brain or inside the skull (see signs of bleeding above),
• 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 (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.

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),
• local swelling,
• blood collection (hematoma) in the groin area as a complication of cardiac catheterization procedure 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 white granulocytic blood cells, causing lung inflammation (eosinophilic pneumonia).

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

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

Reporting of adverse reactions
If you experience any adverse reactions, including any not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions 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 Warszawa
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 provide more information on the safety of the medicine.

5. How to store Mibrex

Keep the 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 indicated.
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 pack and other information

What Mibrex contains

• The active substance is rivaroxaban. Each hard capsule contains 10 mg of rivaroxiban.
• The other ingredients are:
  Capsule contents: monohydrate lactose, microcrystalline cellulose, sodium croscarmellose, hypromellose, sodium lauryl sulphate, magnesium stearate.
  Capsule shell: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172) and black iron oxide (E 172).

What Mibrex looks like and contents of the pack
Mibrex 10 mg hard capsules contain a white or almost white powder, placed in a size 3 capsule (approximately 16 mm in length) with a beige opaque cap and body.
The hard capsules are contained in PVC/PVDC/Aluminium or Aluminium/OPA/Aluminium/PVC blisters, packed in a cardboard box.
Mibrex 10 mg is available in packs containing 10, 15, 20, 30 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