Mibrex

Package leaflet: Information for the patient

Mibrex 15 mg film-coated tablets
Mibrex 20 mg film-coated tablets
Starter pack
Do not use in children.
Rivaroxaban

Please read all of this leaflet carefully before taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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 and is used in adults to:

• 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 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 to form blood clots.

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 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 patency of a venous or arterial catheter,
• if the patient has liver disease leading to an increased risk of bleeding,
• if the patient is pregnant or breastfeeding.

Do not use Mibrex and inform your doctor if you suspect that any of the above circumstances apply to you.
Warnings and precautions
Talk to your doctor or pharmacist before starting to take Mibrex.
Exercise special caution when using Mibrex:

• if the patient has an increased risk of bleeding, such as in the following conditions:
  • severe kidney disease, as 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 patency of a venous or arterial catheter (see section "Mibrex with other medicines"),
  • bleeding 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 oesophagitis (throat and oesophagus), e.g., due to gastro-oesophageal reflux disease (acid reflux into the oesophagus) or tumours located in the stomach or intestines or in the reproductive or urinary system,
  • blood vessel disease in the back of the eye (retinopathy),
  • lung disease in which bronchi are dilated and 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 if surgery or other treatment to remove a blood clot from the lungs is planned. If you suspect that any of the above conditions apply to you, inform your 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 taking Mibrex at the specified time before and after surgery,
• if catheterisation 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 of the legs, or disturbances in bowel or bladder function occur after the anaesthesia wears off.

Children and adolescents
The Mibrex starter pack is not recommended for patients under 18 years of age,
as it is specifically designed for initiating treatment in adult patients and is not suitable for use in children and adolescents.
Mibrex with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription.

• If the patient is taking

some medicines used to treat fungal infections (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),
some antibiotics (e.g., clarithromycin, erythromycin),
some 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,
some medicines used to treat depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs)).
If you suspect that any of the above conditions apply to you, inform your 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 believes 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 you suspect that any of the above conditions apply to you, inform your 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 you are 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 this 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 the doctor or pharmacist.
Mibrex should be taken with food.
The tablet(s) should be swallowed whole, preferably with water.
If the patient has difficulty swallowing the whole tablet, discuss alternative
methods of taking Mibrex with the doctor. The tablet may be crushed and mixed
with water or apple puree immediately before administration. The meal should be taken
immediately after this mixture.
If necessary, the doctor may administer crushed Mibrex tablets through a gastric tube.
How many tablets to take
The recommended dose is one Mibrex 15 mg tablet twice daily for the first 3 weeks.
For treatment after 3 weeks, the recommended dose is one Mibrex 20 mg tablet once daily.
The starter pack of Mibrex 15 mg and Mibrex 20 mg is intended only for the
first 4 weeks of treatment.
After completing the tablets from this pack, treatment will continue with Mibrex 20 mg
once daily, following consultation with the doctor.
If the patient has kidney problems, 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 forming.
When to take Mibrex
The tablet(s) should be taken every day until the doctor decides to stop treatment.
It is best to take the tablet at the same time each day, as this makes it easier to remember.
The doctor will decide how long treatment should continue.
Taking more Mibrex than recommended
If the patient has taken more Mibrex than recommended, contact the
doctor immediately. Taking too high a dose of Mibrex increases the risk of bleeding.
Missed dose of Mibrex

• If the patient is taking 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 within one 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, continue taking one 15 mg tablet twice daily.
• If the patient is taking one 20 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 taking one tablet once daily.

Stopping Mibrex treatment
Do not stop taking Mibrex without first consulting the doctor, as
Mibrex helps prevent a serious condition.
If there are any further questions about the use of this medicine, consult the
doctor.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
As with other medicines of similar action that reduce blood clot formation, Mibrex
may cause bleeding, which potentially can be life-threatening. Excessive bleeding
can lead to a sudden drop in blood pressure (shock). Signs of bleeding are not always 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 paralysis, vomiting, seizures, decreased level of consciousness and neck stiffness. A serious, acute 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 of the patient or a change in treatment is necessary.
  • Signs of severe skin reactions:
• widespread, acute skin rash, blistering 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 (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:
Common (may occur in 1 in 10 patients)

• decrease in red blood cells, which may cause skin pallor and lead to weakness or shortness of breath,
• bleeding from the stomach or intestines, 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 white part of the eye),
• bleeding into tissues or body cavities (hematoma, bruising),
• presence of blood in sputum (hemoptysis) during coughing,
• bleeding from the skin or under the skin,
• 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 loss of strength and energy (weakness, fatigue), headache, dizziness,
• rash, itching of the skin,
• increased activity of certain liver enzymes, which may be evident in blood test results.

Uncommon (may occur in 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, 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 bilirubin levels, increased activity of certain pancreatic or liver enzymes, or increased platelet count,
• fainting,
• malaise,
• rapid heartbeat,

Rare (may occur in 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 as a complication of cardiac catheterization procedure when the catheter is inserted into an artery in the leg (pseudoaneurysm).

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

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

Frequency not known (frequency cannot be estimated from available data)

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

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms 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 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 provide more information on the safety of the 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 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 that following "Lot/LOT" indicates the batch number.
No special storage instructions apply for this medicine.
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 measures help protect the environment.

6. Contents of the package and other information

What Mibrex contains

• The active substance is rivaroxaban. Each coated tablet contains either 15 mg or 20 mg of rivaroxaban.
• Other ingredients are:
  Tablet core: sodium lauryl sulfate, lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose, magnesium stearate;
  Coating of the 15 mg tablet (Opadry II Pink 33G240024): hypromellose, titanium dioxide (E 171), lactose monohydrate, polyethylene glycol 3350, triacetin, iron oxide red (E 172), iron oxide black (E 172);
  Coating of the 20 mg tablet (Opadry II Red 33G250007): hypromellose, titanium dioxide (E 171), lactose monohydrate, polyethylene glycol 3350, triacetin, iron oxide red (E 172).

What Mibrex looks like and contents of the pack
Mibrex 15 mg are pink, round, biconvex coated tablets, embossed with the number "15" on one side.
Mibrex 20 mg are brownish-red, round, biconvex coated tablets, embossed with the number "20" on one side.
The starter pack for the first 4 weeks of treatment: each pack containing 49 coated tablets for the first 4 weeks of treatment includes:
42 coated tablets of Mibrex 15 mg and 7 coated tablets of Mibrex 20 mg.

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