Package leaflet: Information for the user

Mantreda, 15 mg, film-coated tablets
Mantreda, 20 mg, film-coated tablets
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 only. 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.

Contents of the leaflet

What Mantreda is and what it is used for
What you need to know before you take Mantreda
How to take Mantreda
Possible side effects
How to store Mantreda
Contents of the pack and other information

1. What Mantreda is and what it is used for

Mantreda contains the active substance rivaroxaban and is used in adults to:

prevent blood clots in the brain (stroke) and in other blood vessels of the body in patients who have 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 the recurrence of blood clots in the blood vessels of the legs and/or lungs.

Mantreda 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.

Mantreda 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 Mantreda

When not to take Mantreda

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 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 Mantreda, 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 taking Mantreda.
When to be especially careful when taking Mantreda

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, because 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 "Mantreda with other medicines")
- bleeding disorders
- very high blood pressure that does not decrease despite medication
- stomach or intestinal diseases 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, intestines, genital or urinary system
- blood vessel disease at the back of the eye (retinopathy)
- lung disease with dilated airways 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 abnormal blood pressure or if surgery or another 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 taking Mantreda. The doctor will decide whether to use this medicine and whether
the patient should be placed under particularly close observation.
If the patient needs to undergo surgery:

strictly follow the doctor's instructions regarding the timing of taking Mantreda before or after surgery.
if a lumbar puncture or placement of a spinal catheter is planned during surgery (e.g. for epidural or spinal anaesthesia or pain relief):
- strictly follow the doctor's instructions regarding the timing of taking Mantreda before and after the puncture or removal of the catheter
- immediately inform the doctor if, after the anaesthesia wears off, the patient experiences symptoms such as: numbness, weakness in the lower limbs, difficulty passing stool or urinary problems, as immediate treatment is required in such cases.

Children and adolescents
Mantreda tablets are not recommended for children weighing less than 30 kg. There are
insufficient data on the use of the medicine in children and adolescents for the indications approved for
adults.
Mantreda 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:
- certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are applied only topically to 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 (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs)).

If you suspect that any of the above conditions apply to you, inform your doctor
before taking Mantreda, because the effect of Mantreda may be increased. The doctor will decide whether to use this medicine and whether the patient should be placed under
particularly close observation.
If the doctor considers that the patient has an increased risk of developing stomach or duodenal ulcers, 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 you suspect that any of the above conditions apply to you, inform your doctor
before taking Mantreda, because the effect of Mantreda may be reduced. The doctor will decide whether to use Mantreda and whether the patient should be placed under
particularly close observation.
Pregnancy and breastfeeding
Do not take Mantreda 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 Mantreda. If the patient becomes pregnant while taking this medicine, she should immediately inform the doctor, who will decide on further treatment.
Driving and operating machinery
Mantreda 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.
Mantreda 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 of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to take Mantreda

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Mantreda should be taken with food.
The tablet(s) should be swallowed whole, preferably with water.
If a patient has difficulty swallowing the whole tablet, they should discuss alternative ways of taking Mantreda with their doctor. The tablet may be crushed and mixed with water or soft food such as apple puree immediately before administration. A meal should be taken immediately after this mixture.
If necessary, a doctor may administer crushed Mantreda 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 20 mg Mantreda tablet taken once daily. If the patient has kidney problems, the dose may be reduced to one 15 mg Mantreda tablet once daily.
If a patient requires a procedure to unblock blood vessels in the heart (called percutaneous coronary intervention – PCI with stent placement), there is limited evidence supporting dose reduction to one 15 mg Mantreda tablet once daily (or one 10 mg Mantreda tablet once daily in case of renal impairment), in combination with an antiplatelet medicine such as clopidogrel.
- For treatment of blood clots in the veins of the legs, blood clots in the lung blood vessels, and prevention of recurrence of blood clots: The recommended dose is one 15 mg Mantreda tablet twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one 20 mg Mantreda 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 problems and is taking one 20 mg Mantreda tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one 15 mg Mantreda tablet once daily, if the risk of bleeding is greater than the risk of further blood clots.
Children and adolescents The dose of Mantreda depends on body weight and will be calculated by the doctor.
- The recommended dose for children and adolescents with body weight from 30 kg to below 50 kg is one 15 mg Mantreda tablet once daily.
- The recommended dose for children and adolescents with body weight of 50 kg or more is one 20 mg Mantreda tablet once daily.

Each dose of Mantreda should be taken with food and with a drink (e.g. water or juice). Tablets should be taken daily at approximately the same time. It may be helpful to set an alarm as a reminder. For parents or caregivers: observe the child to ensure they have taken the full dose.

The dose of Mantreda depends on body weight, so it is important to attend scheduled appointments with the doctor, 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 tablet to obtain partial doses. If a lower dose is required, another pharmaceutical form of rivaroxaban, such as granules for oral suspension, should be used. For children and adolescents who cannot swallow whole tablets, rivaroxaban in the form of granules for oral suspension should be used.
If the oral suspension is not available, the tablet may be crushed and mixed with water or apple puree immediately before administration. A meal should be taken immediately after this mixture.
If necessary, a doctor may also administer crushed Mantreda tablets through a gastric tube.

If a dose is vomited or expelled

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

Contact your doctor if there are repeated episodes of vomiting or expelled doses after taking Mantreda.

When to take Mantreda
Take one tablet(s) every day until your 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.
Your 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 your heart rhythm needs to be restored to normal rhythm by a procedure called cardioversion, Mantreda should be taken as directed by your doctor.

Missed dose of Mantreda

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 one day to make up for the missed dose. Take the next tablet the following day, then continue taking 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 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.

Taking more Mantreda than prescribed
If a patient takes more Mantreda than prescribed, contact a doctor immediately. Taking too high a dose of Mantreda increases the risk of bleeding.

Stopping Mantreda treatment
Do not stop taking Mantreda without first consulting your doctor, as Mantreda treats and prevents serious medical 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 medicine can cause adverse reactions, although not everyone experiences them.
As with other medicines of similar action that reduce blood clot formation, Mantreda may cause bleeding, which potentially can 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 must contact a doctor immediately if the patient or the patient's child experiences any of the following adverse reactions:

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, sudden 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. The 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 with eosinophilia and systemic symptoms (DRESS syndrome), characterized by rash, fever, internal organ inflammation, blood abnormalities and systemic involvement. The frequency of these adverse reactions is very rare (may occur in less than 1 in 10,000 people).
Signs of severe allergic reactions
- swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; urticaria and breathing difficulties; sudden drop in blood pressure. Severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may occur in less than 1 in 10,000 people) or uncommon (angioedema and allergic edema; may occur in less than 1 in 100 people).

General list of possible adverse reactions in adults as well as in children and adolescents
Common (may occur in 1 in 10 people)

decreased number of red blood cells, which may cause paleness of the skin 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 heavy 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
bleeding from the skin or subcutaneous bleeding
postoperative bleeding
oozing of blood or fluid from the 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, itching of the skin
increased activity of certain liver enzymes, which may be seen in blood test results.

Uncommon (may occur in 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
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 (may occur in 1 in 1,000 people)

bleeding into muscles
cholestasis (bile stasis), hepatitis including liver cell damage
yellowing of the skin and eyes (jaundice)
local swelling
accumulation of blood (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 people)

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

Frequency unknown (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 kidneys being unable to function properly (nephropathy associated with anticoagulant drug use)
increased pressure in the muscles of arms and legs following bleeding, which may lead to 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 Mantreda 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 in 10 people)

headache
fever
nosebleeds, vomiting

Common (may occur in 1 in 10 people)

rapid heartbeat
blood test results may show increased bilirubin levels (a bile pigment)
thrombocytopenia (low platelet count – cells that help in blood clotting)
excessive menstrual bleeding

Uncommon (may occur in 1 in 100 people)

blood test results may show increased levels of a subcategory of bilirubin (direct bilirubin, a bile pigment)

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, 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 181 C
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 provide more information on the safety of the medicine.

5. How to store Mantreda

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on each blister
after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicinal product.
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 Mantreda contains

The active substance in Mantreda is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.
Other ingredients are:
Tablet core: sodium lauryl sulfate, lactose monohydrate, hypromellose 2910, sodium croscarmellose, magnesium stearate.
Coating for 15 mg tablets: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, yellow iron oxide (E 172), red iron oxide (E 172).
Coating for 20 mg tablets: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, red iron oxide (E 172).

What Mantreda looks like and contents of the pack
Mantreda 15 mg, coated tablets, are orange, approximately 7 mm in diameter, with an embossed „T” on one side and „3R” on the other side.
Mantreda 20 mg, coated tablets, are red, approximately 8 mm in diameter, with an embossed „T” on one side and „7R” on the other side.
Mantreda 15 mg: unit dose blisters containing 14 x 1, 28 x 1, 42 x 1 or 100 x 1 tablets.
Mantreda 20 mg: unit dose blisters containing 14 x 1, 28 x 1 or 100 x 1 tablets.

Marketing Authorisation Holder:
Sigillata Limited
Inniscarra
Main Street
Rathcoole
Co. Dublin D24 E029
Ireland

Importer:
Balkanpharma - Dupnitsa AD
3 Samokovsko Shosse Str.
2600 Dupnitsa
Bulgaria

This medicinal product is authorised in the member states of the European Economic Area under the following names:
Germany: Mantreda 15 mg, 20 mg, filmtabletten
Poland: Mantreda