Razarxo

Package leaflet: Information for the patient

Razarxo, 2.5 mg, film-coated tablets
Rivaroxabanum
Please read this leaflet carefully before taking this medicine, as it contains
important information for the patient.

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

Table of contents

1. What Razarxo is and what it is used for
2. Important information before taking Razarxo
3. How to take Razarxo
4. Possible side effects
5. How to store Razarxo
6. Contents of the pack and other information

1. What Razarxo is and what it is used for

You have been prescribed Razarxo because

• you have been diagnosed with acute coronary syndrome (a condition including heart attack and unstable angina, i.e. acute chest pain) and elevated levels of cardiac biomarkers have been confirmed. Razarxo reduces, in adults, the risk of further heart attacks or the risk of death due to heart or blood vessel disease. Razarxo will not be given to you as a single treatment. Your doctor will also prescribe:
  • acetylsalicylic acid, or
  • acetylsalicylic acid and clopidogrel or ticlopidine.

or

• you have been diagnosed with a high risk of blood clots due to coronary artery disease or peripheral arterial disease causing symptoms. Razarxo reduces, in adults, the risk of blood clots (atherothrombotic events). Razarxo will not be given to you as a single treatment. Your doctor will also prescribe acetylsalicylic acid. In certain cases, if you are receiving Razarxo after a procedure to unblock a narrowed or blocked artery in the lower limb to restore blood flow, your doctor may also prescribe clopidogrel to be taken in addition to acetylsalicylic acid for a short period.

Razarxo contains the active substance rivaroxaban and 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 Razarxo

When not to use Razarxo

• if the patient is allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6),
• if the patient has active 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 anticoagulant medicines (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 been diagnosed with acute coronary syndrome and previously experienced bleeding or blood clot in the brain (stroke),
• if the patient has been diagnosed with coronary artery disease or peripheral arterial disease and previously had intracranial bleeding (stroke), or blockage of small arteries supplying blood to tissues in deep brain structures (lacunar stroke), or if the patient had a non-lacunar ischemic stroke within the last month,
• if the patient has a liver disease that increases the risk of bleeding,
• if the patient is pregnant or breastfeeding. Do not use Razarxo, and inform your doctor if you suspect any of the above conditions apply.

Warnings and precautions
Before starting Razarxo, consult your doctor or pharmacist.
Razarxo should not be used in combination with anticoagulant medicines other than acetylsalicylic acid, clopidogrel or ticlopidine, such as prasugrel or ticagrelor.
When to exercise particular caution when using Razarxo

• 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,
  • use of other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is used to maintain catheter patency in a vein or artery (see section "Razarxo with other medicines"),
  • coagulation 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 esophagus (e.g. due to gastroesophageal reflux disease [acid reflux into the esophagus]) or tumors located in the stomach, intestines, genital or urinary system,
  • vascular disease of the posterior part of the eyeball (retinopathy),
  • lung disease with bronchiectasis (dilated bronchi filled with pus) or previous pulmonary hemorrhage,
  • if the patient is over 75 years of age,
  • if the patient weighs less than 60 kg,
  • coronary artery disease with severe symptomatic heart failure,
• 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 a change in treatment is necessary.

If you suspect any of the above conditions apply, inform your doctor before using Razarxo. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the patient needs surgery

• strictly follow the doctor's instructions regarding the timing of Razarxo administration before or after surgery,
• if during surgery spinal catheterization or spinal puncture (e.g. for epidural or spinal anesthesia, or pain relief) is planned:
  • it is very important to take Razarxo 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 anesthesia wears off.

Children and adolescents
Razarxo 2.5 mg tablets are not recommended for patients under 18 years of age. There is insufficient data on the use of this medicine in children and adolescents.
Razarxo with other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently taken, including those obtained without a prescription.

• If the patient is taking
  • certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless 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 (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, prasugrel and ticagrelor (see section "Warnings and precautions")),
  • 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 you suspect any of the above conditions apply, inform your doctor before using Razarxo, as the effect of Razarxo may be enhanced. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the doctor considers the patient to be at increased risk of developing stomach or intestinal ulcers, preventive treatment may be prescribed.

• If the patient is taking
  • certain antiepileptic medicines (phenytoin, carbamazepine, phenobarbital),
  • St. John's wort ( Hypericum perforatum ), a herbal remedy used for depression,
  • rifampicin, an antibiotic.

If you suspect any of the above conditions apply, inform your doctor before using Razarxo, as the effect of Razarxo may be reduced. The doctor will decide whether to use Razarxo and whether the patient requires particularly close monitoring.
Pregnancy, breastfeeding and fertility
Do not use Razarxo 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 Razarxo. If the patient becomes pregnant while taking this medicine, inform the doctor immediately, who will decide on further management.
Driving and operating machinery
Razarxo may cause dizziness (common side effects) and 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.
Razarxo contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means the medicine is considered "sodium-free".

3. How to take Razarxo

This medicine should always be taken as directed by the physician. If in doubt, consult the doctor or pharmacist.
How many tablets to take
The recommended dose is one 2.5 mg tablet twice daily. Razarxo should be taken at approximately the same time each day (for example, one tablet in the morning and one in the evening).
This medicine can be taken with or without food.
If the patient has difficulty swallowing the whole tablet, discuss alternative methods of taking Razarxo with the doctor. The tablet may be crushed and mixed with water or soft food, such as apple puree, immediately before administration.
If necessary, the doctor may administer crushed Razarxo tablets via a gastric tube.
Razarxo will not be given to the patient as the sole medication.
The doctor will prescribe acetylsalicylic acid for the patient to take.
If the patient is receiving Razarxo after an acute coronary syndrome, the doctor may also prescribe clopidogrel or ticlopidine.
If the patient is receiving Razarxo after a procedure to restore blood flow in a narrowed or blocked artery of the lower limb, the doctor may also prescribe clopidogrel to be taken for a short period in addition to acetylsalicylic acid.
The doctor will inform the patient of the dosage to take (usually 75–100 mg acetylsalicylic acid per day, or a daily dose of 75–100 mg acetylsalicylic acid plus a daily dose of 75 mg clopidogrel, or the standard daily dose of ticlopidine).
When to start taking Razarxo
Treatment with Razarxo after acute coronary syndrome should be initiated as soon as possible after stabilization of the acute event, no earlier than 24 hours after hospital admission and at the time when parenteral (by injection) anticoagulant treatment would normally be discontinued.
The doctor will inform the patient when to start treatment with Razarxo if coronary artery disease or peripheral arterial disease has been diagnosed.
The doctor will decide how long treatment should continue.
Taking more than the recommended dose of Razarxo
If the patient has taken more than the recommended dose of Razarxo, contact the doctor immediately. Taking too high a dose of Razarxo increases the risk of bleeding.
Missing a dose of Razarxo
Do not take a double dose to make up for a missed dose. If the patient misses a dose, the next dose should be taken at the scheduled time.
Stopping treatment with Razarxo
Razarxo should be taken regularly and for the duration prescribed by the doctor.
Do not stop taking Razarxo without first consulting the doctor. If treatment with this medicine is discontinued, the risk of a subsequent heart attack, stroke, or death due to heart or blood vessel disease may increase.
If there are any further questions about the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will
experience them.
As with other medicines with a similar anticoagulant effect, the medicine Razarxo
can cause bleeding, which may 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 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 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

• extensive, acute skin rash, blistering or lesions on mucous membranes, e.g. in the mouth or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• drug reaction causing rash, fever, internal organ inflammation, haematological and systemic disorders (DRESS syndrome). The frequency of these adverse reactions is very rare (up to 1 in 10,000 patients).

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. The frequency of severe allergic reactions is very rare (anaphylactic reactions, including anaphylactic shock, may occur in up to 1 in 10,000 individuals) and uncommon (angioedema and allergic oedema may occur in up to 1 in 100 individuals).

General list of possible adverse reactions
Common (may occur in up to 1 in 10 people)

• reduction in red blood cells, which may cause paleness of the skin and lead to weakness or shortness of breath,
• bleeding from the stomach or intestine, bleeding from the genitourinary system (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding from gums,
• bleeding into the eye (including bleeding from the sclera of the eye),
• bleeding into tissues or body cavities (haematoma, bruising),
• presence of blood in sputum (haemoptysis) 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, diarrhoea,
• 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 up to 1 in 100 people)

• bleeding into the brain or inside the skull (see signs of bleeding above),
• bleeding into a joint causing pain and swelling,
• thrombocytopenia (low number of platelets, 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,
• dryness of the mouth,
• urticaria.

Rare (may occur in up to 1 in 1,000 people)

• bleeding into muscles,
• cholestasis (bile stasis), hepatitis, including liver cell damage,
• yellowing of the skin and eyes (jaundice),
• localised swelling,
• accumulation of blood (haematoma) in the groin area as a complication of cardiac catheterisation procedure, when the catheter is inserted into an artery in the leg (pseudoaneurysm).

Very rare (may occur in up to 1 in 10,000 people)

• accumulation of eosinophils, a type of white granulocytic 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 presence of blood in urine, leading to impaired kidney function (drug-induced anticoagulant-related nephropathy),
• 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).

Reporting of adverse reactions
If any adverse symptoms occur, including any possible 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 Reactions
of Medicinal Products at 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 may also be reported to the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Razarxo

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 after the abbreviation "EXP". The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What Razarxo contains

• The active substance is rivaroxaban. Each coated tablet contains 2.5 mg of rivaroxaban.
• The other ingredients are: mannitol, microcrystalline cellulose, polyethylene glycol 8000, poloxamer 188, sodium lauryl sulfate, sodium croscarmellose, colloidal anhydrous silica, sodium stearyl fumarate in the tablet core; hypromellose 2910 - 15 cP, polyethylene glycol 4000, titanium dioxide (E 171), and yellow iron oxide (E 172) in the tablet coating. See section 2, "Razarxo contains sodium".

What Razarxo looks like and contents of the pack
Light brownish-yellow to brownish-yellow, round, slightly biconvex coated tablets with the imprint "2.5" on one side of the tablet. Dimensions: approximately 6.5 mm in diameter.
Razarxo is available in boxes containing:

• 10, 15, 30, 60, 90 and 100 coated tablets in non-perforated blister packs.
• 10 x 1, 30 x 1, 60 x 1, 90 x 1 and 100 x 1 coated tablets in single-dose perforated blister packs.
• calendar packs: 14, 28, 42, 56, 98 coated tablets in non-perforated blister packs.

A patient warning card is included with each medicine package.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

Manufacturer/Importer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Tel: + 48 22 573 75 00