Patient Information Leaflet

Mibrex, 15 mg, coated tablets
Mibrex, 20 mg, coated tablets
Rivaroxaban
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet so that you can read it again if needed.
If you have any further questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm other people, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

What Mibrex is and what it is used for
Important information before taking Mibrex
How to take Mibrex
Possible side effects
How to store Mibrex
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 the formation of blood clots in the brain (stroke) and in other blood vessels in the body in patients with a type of irregular heart rhythm 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 with body weight of 30 kg or more to:

treat blood clots and to 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 for treating 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 for blood clots to form.

2. Important information before using Mibrex

When not to use 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 leads to an increased risk of serious bleeding (e.g. stomach ulcer, trauma or bleeding into the brain, recent surgery of 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 a catheter in a vein or artery,
if the patient has a liver disease that leads to an increased risk of bleeding,
if the patient is pregnant or breastfeeding. Do not use Mibrex and inform your doctor if the patient suspects that any of the above circumstances apply.

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

if the patient has an increased risk of bleeding, such as in the following conditions:
- severe kidney disease in adults and moderate or severe kidney disease in children and adolescents, since kidney function may affect the amount of medicine acting in the patient's body,
- taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is administered to maintain the patency of a catheter in a vein or artery (see section "Mibrex with other medicines"),
- blood clotting disorders,
- very high blood pressure that does not decrease despite 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 in the back of the eyeball (retinopathy),
- lung disease with dilated airways filled with pus (bronchiectasis) or previous bleeding from the lungs,
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 should be changed,
if the patient has abnormal blood pressure or is scheduled for surgery or other treatment to remove a blood clot from the lungs. If the patient suspects any of the above conditions, inform the doctor before using 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:

strictly follow the doctor's instructions regarding the timing of taking Mibrex before and after surgery,
if catheterization or spinal puncture (e.g. for epidural or spinal anaesthesia or pain relief) is planned during surgery:
- it is very important to take Mibrex before and after the puncture or catheter removal as directed by the doctor,
- due to the need for special caution, 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 tablets are not recommended for children weighing less than 30 kg. There is insufficient data on the use of Mibrex in children and adolescents for the indications approved in adults.

Mibrex with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, 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 they are 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 antibacterial medicines (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 (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs)). If the patient suspects any of the above conditions, inform the doctor before using 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 stomach or intestinal ulcers, preventive treatment may be prescribed.
If the patient is taking certain medicines used to treat epilepsy (phenytoin, carbamazepine, phenobarbital), St John's wort ( Hypericum perforatum ), an herbal medicine used for depression, or rifampicin, which belongs to the group of antibiotics. If the patient suspects any of the above conditions, inform the doctor before using 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 should 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) or 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 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 tablet, meaning the product is considered "sodium-free".

3. How to take Mibrex

This medicine should always be taken as directed by the doctor. If in doubt, consult
your doctor or pharmacist.
Mibrex should be taken with food.
The tablet(s) should be swallowed, preferably with water.
If the patient has difficulty swallowing the whole tablet, discuss alternative ways of taking
Mibrex with the doctor. The tablet may be crushed and mixed with water or apple puree
immediately before administration. A meal should be taken promptly after this mixture.
If necessary, the doctor may administer crushed Mibrex tablets through a gastric tube.

How many tablets to take

Adults
- For prevention of blood clots in the brain (stroke) and other blood vessels in the body: The recommended dose is one Mibrex 20 mg tablet once daily. If the patient has kidney disease, the dose may be reduced to one Mibrex 15 mg tablet 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 Mibrex 15 mg tablet once daily (or one Mibrex 10 mg tablet once daily in case of renal impairment), in combination with an antiplatelet agent such as clopidogrel.
- For treatment of blood clots in the veins of the legs, blood clots in the blood vessels of the lungs, and prevention of recurrence of blood clots: The recommended dose is one Mibrex 15 mg tablet twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one Mibrex 20 mg tablet once daily. After at least 6 months of treatment for blood clots, the doctor may decide to continue treatment with either one 10 mg tablet once daily or one 20 mg tablet once daily. If the patient has kidney disease and is taking one Mibrex 20 mg tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one Mibrex 15 mg tablet once daily, 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 the doctor.
- Recommended dose for children and adolescents with a body weight from 30 kg to below 50 kg is one Mibrex 15 mg tablet once daily.
- Recommended dose for children and adolescents with a body weight of 50 kg or more is one Mibrex 20 mg tablet once daily.

Each dose of Mibrex should be taken with a meal and with a drink (e.g. water or juice).
Tablets should be taken daily at approximately the same time. Consider setting an alarm to remind you.
For parents or caregivers: observe the child to ensure the full dose has been taken.
Since the dose of Mibrex depends on body weight, it is important to attend scheduled doctor’s appointments, as dose adjustments may be needed due to changes in weight.
Never adjust the dose on your own. The doctor will adjust the dose if necessary.
Do not split the tablet to achieve a partial dose. If a lower dose is required, use alternative medicines in the form of granules for oral suspension.
For children and adolescents unable to swallow whole tablets, alternative medicines in the form of granules for oral suspension should be used.
If oral suspension is not available, the Mibrex tablet may be crushed and mixed with water or apple puree immediately before administration. A meal should be taken after this mixture.
If necessary, the doctor may also administer the crushed tablet via a gastric tube.

If a dose is vomited or spat 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 vomiting or spitting out the dose occurs repeatedly after taking Mibrex.

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

If a dose of Mibrex is missed

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

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

Stopping Mibrex treatment
Do not stop taking Mibrex without first consulting your doctor, as Mibrex helps prevent serious illness.
If you have any further questions about the use of this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine may cause adverse reactions, although not everyone will experience them.
As with other drugs that have a similar mechanism of action in reducing 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.
You should contact your doctor immediately 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 paralysis, 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, pallor, dizziness, headache, unexplained swelling, shortness of breath, chest pain, or angina. Your doctor may decide that close monitoring of the patient or a change in treatment is necessary.
- Signs of severe skin reactions:
widespread, acute skin rash, formation of blisters or mucosal lesions, e.g. in the mouth or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis).
drug reaction causing rash, fever, internal organ inflammation, hematological and systemic disorders (DRESS syndrome). The frequency of these adverse reactions is very rare (occurring in up to 1 in 10,000 people).
- Signs of serious allergic reactions
swelling of the face, lips, oral cavity, tongue, or throat; urticaria and breathing difficulties; sudden drop in blood pressure. The frequency of severe allergic reactions is very rare (anaphylactic reactions, including anaphylactic shock, may occur in up to 1 in 10,000 people) and uncommon (angioedema and allergic edema may occur in 1 in 100 people).

General list of possible adverse reactions in adults, children, and adolescents:
Common (may occur in 1 out of 10 patients)

reduction in red blood cell count, which may cause paleness of the skin and lead to weakness or shortness of breath,
gastrointestinal bleeding 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 bleeding from the conjunctiva),
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 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 arterial blood pressure (symptoms may include dizziness or fainting upon standing),
general decrease in strength and energy (weakness, fatigue), headache, dizziness,
rash, skin itching,
increased activity of certain liver enzymes, which may be evident in blood test results.

Uncommon (may occur in 1 out of 100 patients)

intracranial bleeding or bleeding into the brain (see signs of bleeding above),
joint bleeding causing pain and swelling,
thrombocytopenia (low platelet count, blood 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 (may occur in 1 out of 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 as a complication of cardiac catheterization when the catheter is inserted into an artery in the leg (pseudoaneurysm).

Very rare (may occur in 1 out of 10,000 patients)

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

Frequency unknown (frequency cannot be determined from available data)

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

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

headache,
fever,
nosebleeds, vomiting.

Common (may occur in 1 out of 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 (may occur in 1 out of 100 patients)

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

Reporting of adverse reactions
If any symptoms of 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 Reactions of Medicinal Products at 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
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 the 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 stated month.
The marking on the packaging following "EXP" indicates the expiry date, and following "Lot/LOT" indicates the batch number.
No special storage instructions apply.
Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such practices help protect the environment.

6. Contents of the package and other information

What Mibrex contains

The active substance is rivaroxaban. Each 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;
coating of the 15 mg tablet (Opadry II Pink 33G240024): hypromellose, type 2910 (6 mPas), titanium dioxide (E 171), lactose monohydrate, polyethylene glycol 3350, triacetin, red iron oxide (E 172), black iron oxide (E 172);
coating of the 20 mg tablet (Opadry II Red 33G250007): hypromellose, type 2910 (6 mPas), titanium dioxide (E 171), lactose monohydrate, polyethylene glycol 3350, triacetin, red iron oxide (E 172), yellow iron oxide (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" engraved on one side.
The tablets are contained in transparent blisters packed in cardboard boxes containing 10, 14, 28, 42, 98 or 100 film-coated tablets, or in perforated unit-dose blisters (Aluminium/PVC/PVDC), packed in cardboard boxes containing 10 x 1 tablet or 100 x 1 tablet, or in multipacks containing 10 boxes, each with 10 x 1 film-coated tablet.
Mibrex 20 mg are brownish-red, round, biconvex, film-coated tablets, with the number "20" engraved on one side.
The tablets are contained in transparent blisters packed in cardboard boxes containing 10, 14, 28, 30, 56, 60 or 98 film-coated tablets, or in perforated unit-dose blisters (Aluminium/PVC/PVDC), packed in cardboard boxes containing 10 x 1 tablet or 100 x 1 tablet, or in multipacks containing 10 boxes, each with 10 x 1 film-coated tablet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
tel. + 48 22 364 61 01