Package leaflet: Information for the patient

Razarxo, 15 mg, coated tablets
Razarxo, 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 necessary.
If you have any 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 the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

What Razarxo is and what it is used for
Important information before taking Razarxo
How to take Razarxo
Possible side effects
How to store Razarxo
Contents of the pack and other information

1. What Razarxo is and what it is used for

Razarxo contains the active substance rivaroxaban. Razarxo 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 who have 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.

Razarxo 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.

Razarxo 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 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 leading 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 clots (e.g. warfarin, dabigatran, apixaban or heparin), except when switching anticoagulant therapy or if heparin is administered to maintain patency of an intravenous or arterial catheter,
if the patient has a liver disease causing an increased risk of bleeding,
if the patient is pregnant or breastfeeding.

Do not use Razarxo 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 Razarxo.
When to exercise particular caution with Razarxo

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, because kidney function may affect the amount of medicine acting in the patient’s body,
- taking other medicines that prevent blood clots (e.g. warfarin, etexilate dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is administered to maintain patency of an intravenous or arterial catheter (see section “Razarxo with other medicines”),
- coagulation disorders,
- very high blood pressure that does not decrease despite treatment with medication,
- diseases of the stomach or intestines that may cause bleeding, e.g. inflammation of the intestines and stomach or oesophagitis (inflammation of the oesophagus and throat), e.g. due to gastro-oesophageal reflux disease (acid reflux into the oesophagus) or tumours located in the stomach, intestines, genital or urinary system,
- blood vessel disease in the back of the eye (retinopathy),
- lung disease where the bronchi are dilated and 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 a change in treatment is needed,
if the patient has abnormal blood pressure or is scheduled for surgery or other treatment to remove a blood clot from the lungs.

If you suspect that any of the above conditions apply to you, inform your doctor
before taking Razarxo. The doctor will decide whether to use this medicine and whether the
patient should be placed under particularly close observation.
If you need to undergo surgery

strictly follow your doctor’s instructions regarding when to take Razarxo before or after surgery,
if during surgery a lumbar puncture or placement of a spinal catheter is planned (e.g. for epidural or spinal anaesthesia, or for pain relief):
- it is very important to take Razarxo before and after the puncture or catheter removal as directed by your doctor,
- inform your doctor immediately if, after the anaesthesia ends, the patient
  experiences symptoms such as: numbness or weakness in the lower limbs, bowel or
  bladder dysfunction, as immediate treatment may be necessary.
  Children and adolescents
  Razarxo tablets are not recommended for children weighing less than 30 kg. There is
  insufficient data on the use of Razarxo in children and adolescents for indications approved in
  adults.
  Razarxo 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 you are 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 (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 Razarxo, because the effect of Razarxo may be increased. The doctor will
decide whether to use this medicine and whether the patient should be placed under particularly
close observation.
If your doctor considers that you have an increased risk of developing stomach or intestinal
ulcers, they may prescribe treatment to prevent peptic disease.

If you are 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 Razarxo, because the effect of Razarxo may be reduced. The doctor will
decide whether to use Razarxo and whether the patient should be placed under particularly
close observation.
Pregnancy, breastfeeding and fertility
Do not use Razarxo if you are pregnant or breastfeeding. If there is a risk that you may become
pregnant, you should use an effective method of contraception during treatment with Razarxo. If
you become pregnant while taking Razarxo, inform your doctor immediately. The doctor will
decide on further treatment.
Driving and using machines
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
bicycles, 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 exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Razarxo should be taken with food.
The tablet(s) should be swallowed whole, preferably with water.
If a patient has difficulty swallowing the whole tablet, discuss alternative ways of taking Razarxo with your doctor. The tablet may be crushed and mixed with water or soft food such as apple puree immediately before administration. After taking this mixture, a meal should be consumed promptly.
If necessary, a crushed Razarxo tablet may be administered through a gastric tube by a healthcare professional.

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 Razarxo tablet once daily. If the patient has kidney disease, the dose may be reduced to one 15 mg Razarxo 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 15 mg Razarxo tablet once daily (or one 10 mg Razarxo tablet once daily in case of renal impairment), in combination with an antiplatelet medicine such as clopidogrel.
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: The recommended dose is one 15 mg Razarxo tablet twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one 20 mg Razarxo 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 20 mg Razarxo tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one 15 mg Razarxo tablet once daily, if the risk of bleeding is greater than the risk of further blood clots.
- Children and adolescents The dose of Razarxo 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 15 mg Razarxo tablet once daily.
Recommended dose for children and adolescents with a body weight of 50 kg or more is one 20 mg Razarxo tablet once daily.

Each dose of Razarxo 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 as a reminder. For parents or caregivers: observe the child to ensure the full dose has been taken.
The dose of Razarxo depends on body weight; therefore, 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 on your own. If necessary, the doctor will adjust the dose.
Do not split tablets to achieve partial doses. If a lower dose is required, another formulation containing rivaroxaban, namely granules for oral suspension, should be used.
For children and adolescents unable to swallow whole tablets, a rivaroxaban formulation as granules for oral suspension should be used.
If the oral suspension is not available, the Razarxo tablet may be crushed and mixed with water or apple puree immediately before administration. After taking this mixture, a meal should be consumed. If necessary, the doctor may also administer the crushed tablet via a gastric tube.

If a dose is vomited or spat out

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

Contact your doctor if repeated vomiting or spitting out of the dose occurs after taking Razarxo.

When to take Razarxo
Take the 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 you should continue treatment.
For prevention of blood clots in the brain (stroke) and other blood vessels in the body:
If heart rhythm needs to be restored by a cardioversion procedure, Razarxo should be taken as directed by your doctor.

Missed dose of Razarxo

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

Stopping treatment with Razarxo
Do not stop taking Razarxo without first consulting your doctor, as Razarxo 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 all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
As with other medicines with a similar anticoagulant effect, Razarxo 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 should immediately contact 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 weakness, 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, 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 with eosinophilia and systemic symptoms (DRESS), characterized by rash, fever, internal organ inflammation, hematological abnormalities, and systemic involvement. The frequency of these adverse reactions is very rare (occurring in up to 1 in 10,000 patients).

Signs of severe allergic reactions

Swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing; hives; 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 edema may occur in up to 1 in 100 individuals).

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

Decrease in red blood cell count, which may cause paleness of the skin and lead to weakness or shortness of breath,
Gastrointestinal or intestinal bleeding, bleeding from the genitourinary system (including blood in urine and severe menstrual bleeding), nosebleeds, gum bleeding,
Bleeding into the eye (including conjunctival hemorrhage),
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,
Swelling of limbs,
Limb pain,
Kidney function disorders (may be observed in tests performed by a doctor),
Fever,
Stomach pain, indigestion, nausea, vomiting, constipation, diarrhea,
Low blood pressure (symptoms may include dizziness or fainting upon standing),
Generalized weakness and 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 within the skull (see signs of bleeding above),
Bleeding into a joint causing pain and swelling,
Thrombocytopenia (low platelet count, blood cells involved in 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,
Dry mouth,
Hives.

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),
Localized 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 up to 1 in 10,000 people)

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

Frequency not known (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 (anticoagulant-related nephropathy),
Increased pressure in the muscles of the arms and legs following bleeding, which may cause 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 rivaroxaban were similar in type to those observed in adults and were mostly 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 tests may show increased bilirubin levels (a bile pigment)
Thrombocytopenia (low platelet count, cells involved in blood clotting)
Excessive menstrual bleeding

Uncommon (may occur in 1 in 100 people)

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

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 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 pack after the
abbreviation "EXP". The expiry date refers to the last day of the stated month.
No special storage instructions apply to this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Razarxo contains

The active substance is rivaroxaban. 15 mg: Each coated tablet contains 15 mg of rivaroxaban. 20 mg: Each coated tablet contains 20 mg of rivaroxaban.
Other ingredients are: mannitol, microcrystalline cellulose, macrogol 8000, poloxamer 188, sodium lauryl sulfate, sodium croscarmellose, colloidal anhydrous silica, and sodium stearyl fumarate in the tablet core; and hypromellose 2910 - 15 cP, macrogol 4000, titanium dioxide (E 171), red iron oxide (E 172), and yellow iron oxide (E 172) – only in 15 mg coated tablets in the tablet coating. See section 2, "Razarxo contains sodium".

What Razarxo looks like and contents of the pack
15 mg:
Red-orange to brown-orange, round, slightly biconvex coated tablets imprinted with the mark "15" on one side of the tablet.
Dimensions: diameter approximately 6.5 mm.
20 mg:
Pink to dark pink, round, slightly biconvex coated tablets imprinted with the mark "20" on one side of the tablet.
Dimensions: diameter approximately 7 mm.

Razarxo is available in packs 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 perforated unit-dose 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 medicine, 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