Mantreda

Package leaflet: Information for the user

Mantreda, 10 mg, coated tablets
rivaroxaban
Please read this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• 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 personally. Do not pass it on to others. It may harm someone else, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet contents

1. What Mantreda is and what it is used for
2. What you need to know before taking Mantreda
3. How to take Mantreda
4. Possible side effects
5. How to store Mantreda
6. 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 the formation of blood clots in the veins following hip or knee replacement surgery. Your doctor has prescribed this medicine because the risk of developing blood clots is increased 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.

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 increases the 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 catheter patency in a vein or artery,
• if the patient has a liver disease that increases the risk of bleeding,
• if the patient is pregnant or breastfeeding.

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

• 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 clotting (e.g. warfarin, dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is administered to maintain catheter patency in a vein or artery (see section "Mantreda 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), for example 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 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 increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment needs to be changed
• 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 think 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 needs particularly close monitoring.
If the patient needs to undergo surgery:

• strictly follow the doctor's instructions regarding the timing of taking Mantreda before or after surgery
• if during surgery the patient is scheduled to undergo lumbar puncture or spinal catheter placement (e.g. for epidural or spinal anaesthesia or for pain relief):
  • strictly follow the doctor's instructions regarding the timing of taking Mantreda
  • immediately inform the doctor if, after the anaesthesia ends, the patient experiences symptoms such as: numbness, weakness in the lower limbs, disturbances in bowel movements or bladder function, as immediate treatment will be necessary.

Children and adolescents
Mantreda 10 mg tablets are not recommended for patients under 18 years of age. There is insufficient data on the use of the medicine in children and adolescents.
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 medicines used for 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)
  • certain antibiotics used for bacterial infections (e.g. clarithromycin, erythromycin)
  • certain antiviral medicines used for 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 you think any of the above conditions apply to you, inform your doctor before taking Mantreda, as the effect of Mantreda may be increased. The doctor will decide whether to use this medicine and whether the patient needs particularly close monitoring.
If the doctor considers that the patient has an increased risk of developing stomach or duodenal ulcers, they may prescribe preventive treatment for 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 medicine used for depression
  • rifampicin, which belongs to the group of antibiotics.

If you think any of the above conditions apply to you, inform your doctor before taking Mantreda, as the effect of Mantreda may be reduced. The doctor will decide whether to use Mantreda and whether the patient needs particularly close monitoring.
Pregnancy and breastfeeding
Do not use Mantreda 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 Mantreda. If the patient becomes pregnant while taking this medicine, inform the doctor immediately, who will decide on further treatment.
Driving and using machines
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 contact the 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 as prescribed by the doctor. If in doubt, consult the doctor or pharmacist.

How many tablets to take

• For prevention of blood clots in veins after hip or knee replacement surgery: The recommended dose is one tablet of Mantreda 10 mg taken once daily.
• For treatment of blood clots in the leg veins, blood clots in the blood vessels of the lungs, and prevention of recurrence of blood clots: After at least 6 months of treatment for blood clots, the recommended dose is one tablet of 10 mg once daily or one tablet of 20 mg once daily. The doctor has prescribed Mantreda 10 mg once daily for the patient.

The tablet should be swallowed whole, preferably with water.
Mantreda may be taken with food or independently of meals.
If the patient has difficulty swallowing the whole tablet, they should discuss alternative methods of taking Mantreda with the doctor. The tablet may be crushed and mixed with water or apple puree immediately before administration.
If necessary, the doctor may administer crushed Mantreda tablets via a gastric tube.

When to take Mantreda

Take one tablet 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.

For prevention of blood clots in the veins of the legs after hip or knee replacement surgery:
The first tablet should be taken between 6 and 10 hours after surgery.
In patients undergoing major hip surgery, tablets are usually taken for 5 weeks.
In patients undergoing major knee surgery, tablets are usually taken for 2 weeks.

Taking more Mantreda than prescribed

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

Missed dose

If the patient misses a dose, they should take the tablet as soon as they remember. The next tablet should be taken the following day, and then the tablets should be taken as usual, once daily.
The patient must not take a double dose to make up for a missed dose.

Stopping Mantreda

Do not stop taking Mantreda without first consulting the doctor, as Mantreda helps prevent serious illness.
If there are any further questions about the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
Like other medicines with a similar action that reduce blood clot formation, Mantreda may cause
bleeding, which could potentially 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 effects 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 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 mucosal lesions, e.g. in the mouth or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • drug reaction causing rash, fever, internal organ inflammation, blood disorders and systemic symptoms (DRESS syndrome). The frequency of these adverse effects 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) and uncommon (angioedema and allergic edema: may occur in less than 1 in 100 people).

General list of possible adverse effects
Common (may occur in 1 in 10 people)

• reduced 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 genitourinary system (including blood in urine and heavy menstrual bleeding), nosebleeds, gum bleeding
• bleeding into the eye (including bleeding from the white of the eye)
• bleeding into tissues or body cavities (hematoma, bruising)
• presence of blood in sputum (hemoptysis) during coughing
• bleeding from the skin or subcutaneous bleeding
• bleeding after surgery
• 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, skin itching
• increased activity of certain liver enzymes, which may be evident 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 - 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
• dryness of the 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)
• localized 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 granular white 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-related nephropathy)
• increased pressure within the muscles of arms and legs following bleeding, which may lead to pain, swelling, altered sensation, numbness or paralysis (compartment syndrome following bleeding).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist.
Adverse effects 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
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to 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. These measures will help protect the environment.

6. Contents of the package and other information

What Mantreda contains

• The active substance is rivaroxaban. Each tablet contains 10 mg of rivaroxaban.
• Other ingredients are:
  Core of the tablet: sodium lauryl sulfate, monohydrate lactose, hypromellose 2910, sodium croscarmellose, magnesium stearate.
  Coating: polyvinyl alcohol, titanium dioxide (E 171), macrogol 3350, talc, carmine (E 120), yellow iron oxide (E 172), red iron oxide (E 172).

What Mantreda looks like and contents of the pack
Mantreda 10 mg film-coated tablets are pink, approximately 8 mm in diameter, with "T" embossed on one side and "1R" on the other.
The tablets are contained in:

• Unit dose blisters packed in cardboard boxes containing 10 x 1 or 30 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 10 mg, filmtabletten
Poland: Mantreda