Package leaflet: Information for the user

ZARIXA, 15 mg, hard capsules
ZARIXA, 20 mg, hard capsules
Rivaroxaban
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

Keep this leaflet. 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 person. Do not pass it on to others. This medicine 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.

Leaflet contents

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

1. What ZARIXA is and what it is used for

ZARIXA contains the active substance rivaroxaban.
ZARIXA is used in adults to:

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

ZARIXA 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.

ZARIXA 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 ZARIXA

When not to take ZARIXA

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 anticoagulant medicines (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 that leads to an increased risk of bleeding,
if the patient is pregnant or breastfeeding. ZARIXA must not be used, and the doctor must be informed if the patient suspects that any of the above circumstances apply.

Warnings and precautions
Before starting treatment with ZARIXA, consult a doctor or pharmacist.
When to exercise particular caution when using ZARIXA

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, as kidney function may affect the amount of medicine acting in the patient's body,
- blood clotting disorders,
- taking other medicines that prevent blood clots (e.g. warfarin, edoxaban, dabigatran, apixaban or heparin) when switching anticoagulant therapy or when heparin is administered to maintain patency of an intravenous or arterial catheter (see section "Other medicines and ZARIXA"),
- very high blood pressure that does not decrease despite treatment with medicines,
- diseases of the stomach or intestines 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 or intestines or in the genital or urinary system,
- blood vessel disease in the back of the eye (retinopathy),
- lung disease in which the 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 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 the patient suspects that any of the above conditions apply, the doctor must be informed
before taking ZARIXA. 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:

it is essential to strictly follow the doctor's instructions regarding the timing of taking ZARIXA before or 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 ZARIXA before and after the puncture or catheter removal, as directed by the doctor,
due to the need for special caution, the doctor must be informed immediately if numbness or weakness in the legs, or disturbances in bowel or bladder function occur after the anaesthesia ends.

Children and adolescents
ZARIXA capsules are not recommended for children weighing less than 30 kg.
There is insufficient data on the use of ZARIXA in children and adolescents for the indications approved in adults.
Other medicines and ZARIXA
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 to treat fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are used only topically on the skin,
- ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol),
- certain antibiotics used to treat bacterial infections (e.g. clarithromycin, erythromycin),
- certain antiviral medicines used to treat HIV infection or AIDS (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 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 the patient suspects that any of the above conditions apply, the doctor must be informed
before taking ZARIXA, because the effect of ZARIXA may be enhanced. 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 ulcers in the stomach or duodenum, he may initiate 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 the patient suspects that any of the above conditions apply, the doctor must be informed
before taking ZARIXA, because the effect of ZARIXA may be reduced. The doctor will decide whether to use ZARIXA and whether the patient should be placed under particularly close observation.
Pregnancy and breastfeeding
Do not use ZARIXA if the patient is pregnant or breastfeeding. If there is a risk that the patient may become pregnant, an effective method of contraception must be used during treatment with ZARIXA. If the patient becomes pregnant while taking ZARIXA, she must inform the doctor immediately, who will decide on further treatment.
Driving and using machines
ZARIXA 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.
ZARIXA contains sodium.
The medicine contains less than 1 mmol of sodium (23 mg) per hard capsule, which means it is essentially "sodium-free".

3. How to take ZARIXA

This medicine should always be taken as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
ZARIXA should be taken with food.
The capsule(s) should be swallowed whole, preferably with water.
If a patient has difficulty swallowing the entire capsule, they should discuss alternative ways of taking ZARIXA with their doctor. The contents of the capsule may be mixed with water or soft food, such as apple puree, immediately before administration. After consuming this mixture, the patient should promptly eat a meal.
If necessary, a doctor may administer the contents of the ZARIXA capsule via a gastric tube.

How many capsules 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 ZARIXA capsule once daily. If the patient has kidney problems, the dose may be reduced to one 15 mg ZARIXA capsule 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 ZARIXA capsule once daily (or one 10 mg ZARIXA capsule 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 blood vessels of the lungs, and prevention of recurrence of blood clots: The recommended dose is one 15 mg ZARIXA capsule twice daily for the first 3 weeks. For treatment beyond week 3, the recommended dose is one 20 mg ZARIXA capsule once daily. After at least 6 months of treatment for blood clots, the doctor may decide to continue treatment with either one 10 mg capsule once daily or one 20 mg capsule once daily. If the patient has kidney problems and is taking one 20 mg ZARIXA capsule once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one 15 mg ZARIXA capsule once daily if the risk of bleeding is greater than the risk of further blood clots.

Children and adolescents
The dose of ZARIXA 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 less than 50 kg is one 15 mg ZARIXA capsule once daily.
Recommended dose for children and adolescents with a body weight of 50 kg or more is one 20 mg ZARIXA capsule once daily.

Each dose of ZARIXA should be taken with a meal, accompanied by a drink (e.g. water or juice). Capsules 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 they have taken the full dose.
The dose of ZARIXA is based on body weight, so it is important to attend scheduled doctor appointments, 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 capsule contents to achieve partial doses. If a lower dose is required, a different medicine containing rivaroxaban in the form of granules for oral suspension should be used.
If a patient is unable to swallow the entire capsule, the contents of the ZARIXA capsule may be sprinkled and mixed with water or apple puree immediately before administration. After consuming this mixture, the patient should promptly eat a meal. If necessary, a doctor may also administer the capsule contents via a gastric tube.

If a dose is spit out or vomited

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

Contact your doctor if repeated spitting out or vomiting occurs after taking ZARIXA.

When to take ZARIXA
The capsule(s) should be taken every day until the doctor decides to stop treatment.
It is best to take the capsule(s) at the same time each day, as this makes it easier to remember.
The doctor will decide how long the patient should continue treatment.

Prevention of blood clots in the brain (stroke) and other blood vessels in the body:
If heart rhythm needs to be restored to normal using a cardioversion procedure, ZARIXA should be taken as directed by the doctor.

Missed dose of ZARIXA

Adults, children and adolescents: If the patient takes one 20 mg capsule or one 15 mg capsule once daily and a dose is missed, take the capsule as soon as possible. Do not take more than one capsule in one day to make up for the missed dose. Take the next capsule the following day, then continue taking one capsule once daily.
Adults: If the patient takes one 15 mg capsule twice daily and a dose is missed, take the capsule as soon as possible. Do not take more than two 15 mg capsules in one day. If the patient forgets to take a dose, they may take two 15 mg capsules at the same time to achieve a total of two capsules (30 mg) taken within one day. The next day, resume taking one 15 mg capsule twice daily.

Taking more than the recommended dose of ZARIXA
If a patient has taken too many ZARIXA capsules, contact a doctor immediately. Taking an excessive dose of ZARIXA increases the risk of bleeding.

Stopping ZARIXA treatment
Do not stop taking ZARIXA without first consulting your doctor, as ZARIXA 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, ZARIXA may cause adverse reactions, although not everyone experiences them.
As with other medicines with a similar mechanism of action reducing blood clot formation, ZARIXA may cause bleeding, which potentially could be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). Signs of bleeding are not always obvious or visible.
Contact your doctor immediately 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. 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 syndrome), characterized by rash, fever, internal organ inflammation, hematological abnormalities, and systemic involvement. The frequency of these adverse reactions is very rare (up to 1 in 10,000 people).

Signs of severe 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 in adults, children, and adolescents:
Common (may occur in 1 in 10 people):

Decrease in 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 conjunctival hemorrhage),
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 a surgical wound,
Limb swelling,
Limb pain,
Kidney function disorders (detectable 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),
Generalized weakness and lack of energy (fatigue, tiredness), 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 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 (detectable 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),
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 1 in 10,000 people):

Eosinophilia accumulation, 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 blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy),
Increased pressure in the muscles of 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
Overall, adverse reactions observed in children and adolescents treated with ZARIXA were generally 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, platelets being cells that help in blood clotting),
Excessive menstrual bleeding.

Uncommon (may occur in 1 in 100 people):

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

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

5. How to store ZARIXA

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton after:
Expiry date and on each blister or container after: EXP. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Capsule contents:
The contents of the capsule remain 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. Proper disposal helps protect the environment.

6. Contents of the pack and other information

What ZARIXA contains

The active substance is rivaroxaban. One hard capsule contains 15 mg or 20 mg of rivaroxaban.
Other ingredients are: Contents of 15 mg and 20 mg capsules: mannitol, sodium lauryl sulfate, magnesium stearate. See section 2 "ZARIXA contains sodium". Capsule shell of 15 mg capsule: gelatin, yellow iron oxide (E 172), red iron oxide (E 172). Capsule shell of 20 mg capsule: gelatin, red iron oxide (E 172). Black printing ink: shellac, propylene glycol, potassium hydroxide, iron oxide black (E 172).

What ZARIXA looks like and contents of the pack
ZARIXA 15 mg hard gelatin capsules are size "3", with a yellow body and an orange to red cap, filled with white or almost white powder.
ZARIXA 20 mg hard gelatin capsules are size "3", with an orange to red body and cap, with a black imprint "20" on the body, filled with white or almost white powder.

Zarixa 15 mg
HDPE container with a child-resistant PP closure and tamper-evident ring, containing 14 or 28 hard capsules in a cardboard box.
PVC/PVDC/Aluminum blisters containing 14, 28, or 42 hard capsules in a cardboard box.

Zarixa 20 mg
HDPE container with a child-resistant PP closure and tamper-evident ring, containing 14 or 28 hard capsules in a cardboard box.
PVC/PVDC/Aluminum blisters containing 14, 28, or 56 hard capsules in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Celon Pharma S.A.
ul. Ogrodowa 2A Kiełpin
05-092 Łomianki
tel.: +48 22 75-15-933
e-mail: [email protected]

Manufacturer:
Celon Pharma S.A.
ul. Marymoncka 15
05-152 Kazuń Nowy

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Celon Pharma SA
ul. Ogrodowa 2A Kiełpin
05-092 Łomianki
tel.: +48 22 75 15 933
e-mail: [email protected]