Zarixa

Patient Information Leaflet

ZARIXA 2.5 mg, hard capsules
Rivaroxabanum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as 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 them, 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 ZARIXA is and what it is used for
2. What you need to know before taking ZARIXA
3. How to take ZARIXA
4. Possible side effects
5. How to store ZARIXA
6. Contents of the pack and other information

1. What ZARIXA is and what it is used for

You have been prescribed ZARIXA 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. ZARIXA reduces the risk of subsequent heart attack and reduces the risk of death due to heart or blood vessel disease in adults. ZARIXA will not be given to you as a single treatment. Your doctor will also prescribe you:
  • 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. ZARIXA reduces the risk of blood clots (atherosclerotic thrombotic events) in adults. ZARIXA will not be given to you as a single treatment. Your doctor will also prescribe you acetylsalicylic acid. In some cases, if you are receiving ZARIXA after a procedure to open a narrowed or blocked artery in the lower limb to restore blood flow, your doctor may also prescribe clopidogrel to be taken for a short period in addition to acetylsalicylic acid.

ZARIXA 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 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 is experiencing excessive bleeding,
• if the patient has a disease or condition affecting an organ that increases the risk of serious bleeding (e.g. stomach ulcer, trauma or intracranial bleeding, recent brain or eye surgery),
• 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 has 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 has previously experienced intracranial bleeding (hemorrhagic stroke), occlusion of small arteries supplying blood to tissues in deep brain structures (lacunar stroke), or if the patient has had a blood clot in the brain (ischemic non-lacunar 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.

ZARIXA must not be used, and the doctor must be informed, if the patient
suspects that any of the above-mentioned conditions apply.
Warnings and precautions
Before starting treatment with ZARIXA, consult a doctor or pharmacist. ZARIXA 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 ZARIXA

• 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 anticoagulant medicines (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 "Other medicines and ZARIXA"),
  • coagulation disorders,
  • very high blood pressure that does not decrease despite medication,
  • stomach or intestinal disorders that may cause bleeding, e.g. inflammatory bowel or stomach disease or esophagitis (inflammation of the throat and esophagus), e.g. due to gastroesophageal reflux disease (backflow of stomach acid into the esophagus) or tumors located in the stomach or intestines or in the genital or urinary system,

• retinal vascular disease (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 treatment adjustment is necessary.

If the patient suspects any of the above-mentioned conditions, the doctor must be informed
before taking ZARIXA. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the patient needs surgery:

• it is essential to strictly follow the doctor's instructions regarding the timing of ZARIXA administration before or after surgery,
• if spinal catheterization or spinal puncture (e.g. for epidural or intrathecal anesthesia 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 bowel or bladder dysfunction occur after anesthesia.

Children and adolescents
ZARIXA 2.5 mg capsules are not recommended for patients under 18 years of age. There is insufficient data on the use of the medicine in children and adolescents.
Other medicines and ZARIXA
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use, including those available 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 excessive cortisol),
  • certain antibacterial medicines (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 antidepressants (selective serotonin reuptake inhibitors (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)).

If the patient suspects any of the above-mentioned conditions, the doctor must be informed
before taking ZARIXA, as the effect of ZARIXA may be enhanced. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the doctor considers that the patient has an 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 the patient suspects any of the above-mentioned conditions, the doctor must be informed
before taking ZARIXA, as the effect of ZARIXA may be reduced. The doctor will decide whether to use ZARIXA and whether the patient requires particularly close monitoring.
Pregnancy and breastfeeding
ZARIXA must not be used 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 this medicine, she must inform the doctor immediately, who will decide on further management.
Driving and operating machinery
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, meaning it is essentially "sodium-free".

3. How to take ZARIXA

This medicine should always be taken as directed by the doctor. If in doubt, contact
the doctor or pharmacist.
How many capsules to take
The recommended dose is one 2.5 mg capsule twice daily. ZARIXA should be taken at approximately
the same time each day (for example, one capsule in the morning and one in the evening). This medicine
may be taken with or without food.
If a patient has difficulty swallowing the entire capsule, discuss alternative ways of taking ZARIXA
with the doctor. The contents of the capsule may be mixed with water or soft food, such as apple
purée, immediately before administration.
If necessary, the doctor may administer the contents of the ZARIXA capsule via a gastric tube.
ZARIXA 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 ZARIXA
after an acute coronary syndrome, the doctor may also prescribe clopidogrel or ticlopidine.
If the patient is receiving ZARIXA 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 of acetylsalicylic acid
daily, 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 take ZARIXA
Treatment with ZARIXA after acute coronary syndrome should be initiated as soon as possible after
stabilization of the acute coronary syndrome, no earlier than 24 hours after hospital admission and
at the time when parenteral (by injection) anticoagulant therapy would normally be discontinued.
The doctor will inform the patient when to start treatment with ZARIXA if coronary artery disease
or peripheral arterial disease has been diagnosed.
The doctor will decide how long treatment should continue.
Taking more ZARIXA than prescribed
If a patient has taken more than the prescribed dose of ZARIXA, contact the doctor immediately.
Taking too high a dose of ZARIXA increases the risk of bleeding.
Missing a dose of ZARIXA
Do not take a double dose to make up for a missed dose. If a dose is missed, take the next dose at
the scheduled time.
Stopping ZARIXA
ZARIXA should be taken regularly and for the duration prescribed by the doctor.
Do not stop taking ZARIXA without first consulting the doctor.
If this medicine is discontinued, the risk of another heart attack, stroke, or death due to heart or
blood vessel disease may increase.
If there are any further doubts about the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, ZARIXA may cause adverse reactions, although not everyone experiences them.
As with other medicines with a similar mechanism of action that reduce 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.
You should 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 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, hematological disorders, and systemic involvement. The frequency of these adverse reactions is very rare (up to 1 in 10,000 people).

Signs of serious 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
Common (may occur in 1 out of 10 people)

• Decrease in red blood cells, which may cause paleness of the skin and lead to weakness or shortness of breath,
• Gastrointestinal or intestinal bleeding, bleeding from the urinary or genital tract (including blood in urine and severe 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,
• Skin bleeding or subcutaneous hemorrhage,
• 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 evident in blood test results.

Uncommon (may occur in 1 out of 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, the 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 1 out of 1,000 people)

• Bleeding into muscles,
• Cholestasis (bile stasis), hepatitis, including liver cell damage,
• Yellowing of the skin and eyes (jaundice),
• Localized swelling,
• Blood accumulation (hematoma) in the groin as a complication of cardiac catheterization procedure when the catheter is inserted into the artery in the leg (pseudoaneurysm).

Very rare (may occur in 1 out of 10,000 people)

• Accumulation of eosinophils, a type of granular white blood cells, 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 presence of blood in urine, leading to impaired kidney function (drug-induced nephropathy associated with anticoagulant medicines),
• 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 reactions
If any adverse symptoms 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, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store ZARIXA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box 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.
Contents of the capsule:
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. These measures will help protect the environment.

6. Contents of the pack and other information

What ZARIXA contains

• The active substance is rivaroxaban. One hard capsule contains 2.5 mg of rivaroxaban.
• Other ingredients are:
  Capsule content: mannitol, sodium lauryl sulfate, magnesium stearate. See section 2 "ZARIXA contains sodium".
  Capsule shell: gelatin, titanium dioxide (E 171).
  Black printing ink: shellac, propylene glycol, potassium hydroxide, iron oxide black (E 172).

What ZARIXA looks like and contents of the pack
ZARIXA 2.5 mg hard gelatin capsules are size "3", with a white body and white cap, printed in black with "2.5" on the body, and filled with white or almost white powder.
Packaged in HDPE bottles with child-resistant screw cap made of PP and a tamper-evident seal, or in PVC/PVDC/Aluminium blisters, containing 28 hard capsules in a cardboard box.

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

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

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Celon Pharma S.A.
Ogrodowa 2A Kiełpin
05-092 Łomianki
Poland
Tel.: +48 22 75 15 933
E-mail: [email protected]