Mibrex

Package Leaflet: Information for the User

Mibrex, 15 mg hard capsules

Mibrex, 20 mg hard capsules

Rivaroxaban

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 only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What Mibrex is and what it is used for
• 2. Important information 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. Mibrex is used in adults to:

• prevent blood clots in the brain (stroke) and other blood vessels in the body, if you have a form of irregular heart rhythm called atrial fibrillation not caused by heart valve problems.
• treat blood clots in the veins of the legs (deep vein thrombosis) and blood vessels in the lungs (pulmonary embolism) and prevent new blood clots from forming 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 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. It works by blocking the factor Xa in the blood, which is involved in blood clotting, and thus reduces the tendency to form blood clots.

2. Important information before you take Mibrex

When not to take Mibrex

• if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6),
• if you have bleeding that is not under control,
• if you have a disease or condition that increases the risk of serious bleeding (e.g. stomach ulcer, injury or bleeding in the brain, recent brain or eye surgery),

or if you have recently had a procedure to inject a dye into your blood vessels (e.g. coronary angiography or contrast-enhanced MRI or CT scan) and you have kidney problems.

• if you are taking other medicines to prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin), except when switching to Mibrex or when heparin is given to keep a line or device (such as a dialysis machine) working properly,
• if you have liver disease that increases the risk of bleeding,
• if you are pregnant or breast-feeding.

Do not take Mibrex, and tell your doctor if you think any of the above applies to you.

Warnings and precautions

Before taking Mibrex, talk to your doctor or pharmacist.

When to be extra careful while taking Mibrex

• if you have 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 in the body,
• taking other medicines that prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin) when switching to Mibrex or when heparin is given to keep a line or device (such as a dialysis machine) working properly (see "Mibrex with other medicines"),
• bleeding disorders,
• very high blood pressure that does not come down with treatment,
• stomach or bowel disease that may cause bleeding, such as stomach or bowel ulcers or inflammation of the oesophagus (gullet),
• blood vessel disease in the back of the eye (retinopathy),
• lung disease that causes the airways to widen and fill with pus (bronchiectasis) or previous bleeding in the lungs,
• if you have artificial heart valves,
• if you have a condition called antiphospholipid syndrome (a disease that increases the risk of blood clots), you should tell your doctor, who will decide whether to change your treatment,
• if you have unstable or planned surgery to remove a blood clot from the lungs.

If you think any of the above applies to you, tell your doctor before taking Mibrex

The doctor will decide whether to give you Mibrex and whether you need to be closely monitored.

If you need to have an operation:

• you must follow your doctor's instructions about taking Mibrex before and after the operation,
• if you are going to have a procedure to inject a dye into your blood vessels (e.g. coronary angiography or contrast-enhanced MRI or CT scan) or have a spinal or epidural injection (e.g. to numb the lower part of your body):
• it is very important to take Mibrex before and after the procedure as instructed by your doctor,
• because of the need for extra care, you should immediately tell your doctor if you get numbness or weakness in your legs, problems with your bowels or bladder, or loss of bladder or bowel control after the procedure.

Children and adolescents

Mibrex 15 mg capsules are not recommended for children under 30 kg.
Mibrex 20 mg capsules are not recommended for children under 50 kg.
There is limited experience with the use of rivaroxaban in children and adolescents for the same conditions as in adults.

Mibrex with other medicines

Tell your doctor or pharmacist about all the 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 on the skin,
• ketokonazole tablets (used to treat Cushing's syndrome, a condition where the body produces too much cortisol),
• certain medicines for bacterial infections (e.g. clarithromycin, erythromycin),
• certain antiviral medicines for HIV or AIDS (e.g. ritonavir),
• other medicines that prevent blood clots (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 irregular heart rhythm,
• certain medicines for depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs)).

If you think any of the above applies to you, tell your doctor before taking Mibrex

because the effect of Mibrex may be stronger. The doctor will decide whether to give you Mibrex and whether you need to be closely monitored.

• If you are taking
• certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital),
• St. John's Wort (Hypericum perforatum), a herbal medicine used for depression,
• rifampicin, a type of antibiotic.

If you think any of the above applies to you, tell your doctor before taking Mibrex

because the effect of Mibrex may be weaker. The doctor will decide whether to give you Mibrex and whether you need to be closely monitored.

Pregnancy and breast-feeding

Do not take Mibrex if you are pregnant or breast-feeding. If there is a risk that you may become pregnant, you should use a reliable method of contraception while taking Mibrex. If you become pregnant while taking Mibrex, you should immediately tell your doctor, who will decide on the further course of treatment.

Driving and using machines

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

Mibrex contains lactose monohydrate and sodium

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
The medicine contains less than 1 mmol (23 mg) sodium per capsule, which is essentially "sodium-free".

3. How to take Mibrex

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.
Take Mibrex with food.
Swallow the capsule(s) whole with water.
If you have difficulty swallowing the capsule whole, 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.
After taking the mixture, you should take a meal. If necessary, your doctor may also give the contents of the capsule through a nasogastric tube.

How much to take

Adults

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

If you need a procedure to open up blocked blood vessels in the heart (called percutaneous coronary intervention, or PCI, with stent placement), there is limited evidence to support the use of a reduced dose of one 15 mg Mibrex capsule once a day (or one 10 mg Mibrex capsule once a day in patients with kidney disease) in combination with a medicine that prevents platelets from clumping, such as clopidogrel.

• To treat and prevent blood clots in the veins of the legs and blood vessels in the lungsThe recommended dose is one 15 mg Mibrex capsule twice a day for the first three weeks. After three weeks, the recommended dose is one 20 mg Mibrex capsule once a day. After at least six months of treatment for blood clots, your doctor may decide to continue treatment with one 10 mg Mibrex capsule once a day or one 20 mg Mibrex capsule once a day. If you have kidney disease and are taking one 20 mg Mibrex capsule once a day, your doctor may decide to reduce the dose to one 15 mg Mibrex capsule once a day after three weeks of treatment, if the risk of bleeding is higher than the risk of another blood clot.

Children and adolescents

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

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

Each dose of Mibrex should be taken with food, with a drink (such as water or juice).
The capsules should be taken once a day, at approximately the same time every day. It may be helpful to set an alarm reminder.
For parents or carers: you should check that the child has taken the whole dose.
The dose of Mibrex is based on body weight, so it is important to come to scheduled doctor's appointments, as the dose may need to be adjusted if the child's 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, an alternative rivaroxaban medicine in granule form for oral suspension should be used.
For children and adolescents who are unable to swallow the capsule whole, a rivaroxaban medicine in granule form for oral suspension should be used.
If the oral suspension is not available, the contents of the Mibrex capsule can be mixed with water or apple sauce, immediately before taking. After taking the mixture, a meal should be taken. If necessary, your doctor may also give the contents of the capsule through a nasogastric tube.

If you spit out or vomit the dose

• 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 the dose or have stomach problems and vomit after taking Mibrex.

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 this will help you to remember to take them.
Your doctor will decide how long you should take Mibrex.
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.

If you take more Mibrex than you should

If you have taken more Mibrex capsules than you should, contact your doctor immediately.
Taking more Mibrex than you should increases the risk of bleeding.

If you forget to take Mibrex

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

If you stop taking Mibrex

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
As with other medicines that prevent blood clots, Mibrex may cause bleeding, which can be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). Not all bleeding may be obvious or external.

Immediately tell your doctor if 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 consciousness and stiff neck. This is a serious medical emergency. You should seek medical help immediately!),
• prolonged or excessive bleeding,
• unusual weakness, tiredness, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina. Your doctor may decide to closely monitor you or change your treatment.
• Signs of severe skin reactions:
• widespread, severe skin rash, blistering or skin peeling (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis).
• a reaction that causes a rash, fever, inflammation of internal organs, blood abnormalities and generalised symptoms (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 oedema occur in less than 1 in 100 patients).

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

Common side effects(may affect up to 1 in 10 people)

• reduced number of red blood cells, which can cause pale skin and be the cause of weakness or shortness of breath,
• bleeding from the stomach or bowel, 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 into the retina),
• bleeding into tissues or cavities of the body (haematoma, bruising),
• coughing up blood (haemoptysis),
• bleeding from the skin or bleeding under the skin,
• bleeding after an operation,
• oozing of blood or fluid from the wound after an operation,
• swelling of the limbs,
• limb pain,
• kidney problems (which may be seen in blood tests),
• fever,
• stomach upset, feeling sick (nausea) or vomiting, constipation, diarrhoea,
• low blood pressure (symptoms may include dizziness or fainting when standing up),
• general weakness and lack of energy (fatigue), headache, dizziness,
• rash, itching,
• increased activity of some liver enzymes, which may be seen in blood tests.

Uncommon side effects(may affect up to 1 in 100 people)

• bleeding into the brain or inside the skull (see above signs of bleeding),
• bleeding into a joint, causing pain and swelling,
• low platelet count (thrombocytopenia),
• allergic reactions, including skin allergies,
• liver problems (which may be seen in blood tests),
• blood tests may show increased levels of bilirubin, some liver or pancreatic enzymes, or platelet count,
• fainting,
• feeling unwell,
• rapid heartbeat,
• dry mouth,
• hives.

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

• bleeding into the muscle,
• cholestasis (bile flow obstruction), liver inflammation, including liver cell damage,
• jaundice (yellowing of the skin and eyes),
• localised swelling,
• collection of blood (haematoma) in the groin as a complication of a procedure to insert a catheter into a blood vessel in the leg (pseudoaneurysm).

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

• build-up of eosinophils, a type of white blood cell, which can cause inflammation in the lungs (eosinophilic pneumonia).

Side effects with frequency not known(cannot be estimated from the available data)

• kidney failure after severe bleeding,
• kidney damage due to bleeding, sometimes with blood in the urine, leading to kidney failure (nephropathy caused by anticoagulant medicines),
• increased pressure in the muscles of the arms and legs, occurring after bleeding, which can cause pain, swelling, changes in sensation, numbness or paralysis (compartment syndrome due to bleeding).

Side effects in children and adolescents

Overall, the side effects seen in children and adolescents treated with Mibrex were similar in type to those seen in adults and were mainly mild to moderate.
Side effects that were more common in children and adolescents:

• Very common side effects(may affect more than 1 in 10 people)
• headache,
• fever,
• nosebleeds,
• vomiting.

Common side effects(may affect up to 1 in 10 people)

• rapid heartbeat,
• blood tests may show increased levels of bilirubin,
• low platelet count (thrombocytopenia),
• excessive menstrual bleeding.

Uncommon side effects(may affect up to 1 in 100 people)

• blood tests may show increased levels of a type of bilirubin (direct bilirubin).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in the "Further information" section below.
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 which is stated on the blister and carton after EXP. The expiry date refers to the last day of that month.
PVC/PVDC/Aluminium blisters: Store in a temperature not exceeding 30°C. Store in the original package to protect from moisture.
Aluminium/OPA/Aluminium/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. These 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 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.

Cap: 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 filled in size 1 (approximately 19 mm long) hard capsules with light brown opaque cap and body.
Mibrex 20 mg hard capsules are white or almost white powder filled in size 0 (approximately 22 mm long) hard capsules with dark brown opaque cap and body.
The hard capsules are packaged in PVC/PVDC/Aluminium or Aluminium/OPA/Aluminium/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 Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. +48 22 364 61 01

Manufacturer

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