Zarixa

Package Leaflet: Information for the User

ZARIXA, 15 mg, hard capsules

ZARIXA, 20 mg, hard capsules

Rivaroxaban

Read all of this leaflet carefully before taking this medicine because 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 you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 1. What ZARIXA is and what it is used for
• 2. Important information before you take 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

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

• prevent blood clots in the brain (stroke) and other blood vessels in the body, if you have a form of irregular heartbeat called atrial fibrillation not caused by heart valve problems,
• treat blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism) and prevent blood clots from forming again in the blood vessels of the legs and/or lungs.

ZARIXA is used in children and adolescents aged below 18 years and weighing 30 kg or more to:

• treat and prevent blood clots in the veins or 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 the factor Xa in the blood, which is involved in blood clotting.

2. Important information before you take ZARIXA

When not to take ZARIXA

• if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6),
• if you have bleeding that is not under control,
• if you have a disease or condition that increases the risk of serious bleeding (e.g. stomach ulcer, injury or bleeding in the brain, recent surgery of the brain or eyes),
• if you are taking other medicines to prevent blood clots (e.g. warfarin, dabigatran, apixaban or heparin), except when switching to a different anticoagulant or when heparin is given to maintain catheter patency in a vein or artery,
• if you have liver disease that increases the risk of bleeding,
• if you are pregnant or breast-feeding. You must not take ZARIXA and inform your doctorif you think any of the above applies to you.

Warnings and precautions

Before taking ZARIXA, tell your doctor or pharmacist.

When to be extra careful while taking ZARIXA

• if you have an increased risk of bleeding, such as:
• severe kidney disease in adults and moderate or severe kidney disease in children and adolescents, as kidney function may affect the amount of medicine in the body,
• bleeding disorders,
• taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin) when switching to a different anticoagulant or when heparin is given to maintain catheter patency in a vein or artery (see section "Other medicines and ZARIXA"),
• very high blood pressure that does not decrease with treatment,
• stomach or intestinal diseases that may cause bleeding, such as inflammation of the stomach and intestines or esophagitis (inflammation of the esophagus),
• eye diseases (retinopathy),
• lung disease with dilated bronchi and pus (bronchiectasis) or previous lung bleeding,
• if you have artificial heart valves,
• if you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), you should inform your doctor, who will decide whether to change your treatment,
• if you have abnormal blood pressure or if a surgical procedure is planned to remove a blood clot from the lungs.

If you think any of the above applies to you, tell your doctor

before taking ZARIXA. Your doctor will decide whether to prescribe ZARIXA and whether you should be closely monitored.

If you need to have surgery:

• you must carefully follow your doctor's instructions about taking ZARIXA before or after surgery,
• if a procedure involving catheterization or puncture of the spine (e.g. for epidural or spinal anesthesia or pain relief) is planned:
• it is very important to take ZARIXA before and after the puncture or catheter removal, as instructed by your doctor,
• due to the need for extra caution, you should immediately inform your doctor if you experience numbness or weakness in your legs, bowel or bladder dysfunction after anesthesia.

Children and adolescents

ZARIXA capsules are not recommended for children weighing less than 30 kg.
There is limited experience with the use of ZARIXA in children and adolescents for the indications in adults.

Other medicines and ZARIXA

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription.

If you are taking:

• certain medicines for fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are used only locally on the skin,
• ketokonazole tablets (used to treat Cushing's syndrome, where the body produces too much cortisol),
• certain medicines for bacterial infections (e.g. clarithromycin, erythromycin),
• certain antiviral medicines used to treat HIV or AIDS (e.g. ritonavir),
• other medicines that prevent 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 and noradrenaline reuptake inhibitors (SNRIs)).

If you think any of the above applies to you, tell your doctor

before taking ZARIXA, as the effect of ZARIXA may be increased. Your doctor will decide whether to prescribe ZARIXA and whether you should be closely monitored.
If your doctor thinks you are at increased risk of developing stomach or duodenal ulcers, he may prescribe a medicine to prevent this.

If you are taking

• certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital),
• St. John's Wort (Hypericum perforatum), a herbal medicine used to treat depression,
• rifampicin, an antibiotic.

If you think any of the above applies to you, tell your doctor

before taking ZARIXA, as the effect of ZARIXA may be reduced. Your doctor will decide whether to prescribe ZARIXA and whether you should be closely monitored.

Pregnancy and breast-feeding

Do not take ZARIXA if you are pregnant or breast-feeding. If there is a risk that you may become pregnant, you should use effective contraception during treatment with ZARIXA. If you become pregnant during treatment with ZARIXA, you should inform your doctor immediately, who will decide on further treatment.

Driving and using machines

ZARIXA may cause dizziness (common side effect) and fainting (uncommon side effect) (see section 4, "Possible side effects"). Patients who experience these side effects should not drive, ride a bicycle, or operate tools or machines.

ZARIXA contains sodium

The medicine contains less than 1 mmol sodium (23 mg) per hard capsule, which is essentially "sodium-free".

3. How to take ZARIXA

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
ZARIXA should be taken with food.
Swallow the capsule(s) whole with water.
If you have difficulty swallowing the capsule whole, talk to your doctor about other ways to take ZARIXA. The contents of the capsule can be mixed with water or soft food, such as apple puree, immediately before taking. After such a mixture, you should eat a meal immediately. If necessary, your doctor may also give the contents of the capsule through a gastric tube.

How much to take

Adults

• To prevent 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 you have kidney problems,the dose may be reduced to one 15 mg ZARIXA capsule once daily. If you need a procedure to open up the blood vessels in the heart (called percutaneous coronary intervention, PCI, with stent placement), there is limited evidence to support a dose reduction to one 15 mg ZARIXA capsule once daily (or one 10 mg ZARIXA capsule once daily in case of kidney disease) in combination with an antiplatelet medicine, such as clopidogrel.
• To treat blood clots in the legs, blood clots in the lungs, and to prevent blood clots from forming again: The recommended dose is one 15 mg ZARIXA capsule twice daily for the first 3 weeks. After 3 weeks, the recommended dose is one 20 mg ZARIXA capsule once daily. After at least 6 months of treatment for blood clots, your doctor may decide to continue treatment with one 10 mg capsule once daily or one 20 mg capsule once daily. If you have kidney problems and are taking one 20 mg ZARIXA capsule once daily, your doctor may decide to reduce the dose to one 15 mg ZARIXA capsule once daily after 3 weeks of treatment if the risk of bleeding is higher than the risk of another blood clot.

Children and adolescents

The dose of ZARIXA depends on body weight and will be calculated by your doctor.

• The recommended dose for children and adolescents weighing 30 kg to less than 50 kgis one ZARIXA 15 mgcapsule once daily.
• The recommended dose for children and adolescents weighing 50 kg or moreis one ZARIXA 20 mgcapsule once daily.

Each dose of ZARIXA should be taken with food, with a drink (e.g. water or juice). The capsules should be taken every day at about the same time. It is a good idea to set an alarm reminder.
For parents or caregivers: you should check that the child has taken the whole dose.
The dose of ZARIXA is based on body weight, so it is important to come to scheduled doctor's appointments, as the dose may need to be adjusted due to weight changes.
Never adjust the dose yourself.If necessary, your doctor will adjust the dose.
Do not sprinkle the contents of the capsule to get a partial dose. If a smaller dose is needed, use a different medicine containing rivaroxaban in the form of granules for oral suspension.
If the patient is unable to swallow the capsule whole, the contents of the ZARIXA capsule can be mixed with water or apple puree immediately before taking. After such a mixture, you should eat a meal immediately. If necessary, your doctor may also give the contents of the capsule through a gastric tube.

If you spit out the dose or vomit

• less than 30 minutes after taking ZARIXA - take a new dose.
• more than 30 minutes after taking ZARIXA - do nottake a new dose. In this case, take the next dose of ZARIXA at the usual time.

You should contact your doctor if you spit out the dose or vomit repeatedly after taking ZARIXA.

When to take ZARIXA

The capsule(s) should be taken every day until your doctor decides to stop the treatment.
It is best to take the capsule(s) at the same time every day, as this will help you to remember to take them.
Your doctor will decide how long you should continue to take ZARIXA.
To prevent blood clots in the brain (stroke) and other blood vessels in the body:
If your heart rhythm needs to be restored to normal using a procedure called cardioversion, you should take ZARIXA as instructed by your doctor.

Missing a dose of ZARIXA

• Adults, children and adolescents: If you take one 20 mg or one 15 mg capsule once daily and miss a dose, take it as soon as possible. Do not take more than one capsule in one day to make up for a missed dose. Take the next capsule at the usual time the next day and then continue to take one capsule once daily.
• Adults: If you take one 15 mg capsule twice daily and miss a dose, take it as soon as possible. Do not take more than two 15 mg capsules in one day. If you miss a dose, you may take two 15 mg capsules at the same time to get a total of two capsules (30 mg) in one day. The next day, continue to take one 15 mg capsule twice daily.

Taking too much ZARIXA

If you take more ZARIXA capsules than you should, contact your doctor immediately. Taking too much ZARIXA increases the risk of bleeding.

Stopping ZARIXA treatment

Do not stop taking ZARIXA without talking to your doctor first, as ZARIXA treats and prevents serious diseases.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, ZARIXA can cause side effects, although not everybody gets them.
As with other medicines that prevent blood clotting, ZARIXA may cause bleeding, which can be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). Not all bleeding may be obvious or external.
You must tell your doctor immediatelyif you experience any of the following side effects:

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 stiff neck. This is a serious medical emergency. You should seek medical help immediately!),
• prolonged or excessive bleeding,
• unusual weakness, tiredness, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina. Your doctor may decide to closely monitor you or change your treatment.

Signs of severe skin reactions:

• widespread, severe skin rash, blistering, or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis),
• drug reaction that causes a rash, fever, inflammation of internal organs, blood disorders, and systemic symptoms (DRESS syndrome). The frequency of these side effects is very rare (less than 1 in 10,000 people).

Signs of severe allergic reactions

• swelling of the face, lips, mouth, tongue, or throat; hives; difficulty breathing; sudden drop in blood pressure. The frequency of severe allergic reactions is 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 1 in 100 people).

General list of possible side effects in adults, children, and adolescents:

Common(may affect up to 1 in 10 people):

• decrease in red blood cell count, which may cause pale skin and be the reason for weakness or shortness of breath,
• bleeding from the stomach or intestines, bleeding from the urinary tract (including blood in the urine and heavy menstrual bleeding), nosebleeds, bleeding from the gums,
• bleeding into the eye (including bleeding into the conjunctiva),
• bleeding into tissues or body cavities (hematoma, bruising),
• appearance of blood in sputum when coughing,
• bleeding from the skin or bleeding under the skin,
• bleeding after surgery,
• oozing of blood or fluid from the wound after surgery,
• swelling of the limbs,
• limb pain,
• kidney problems (which can be seen in tests performed by your doctor),
• fever,
• stomach pain, nausea (feeling sick), vomiting, constipation, diarrhea,
• low blood pressure (symptoms may include dizziness or fainting when standing up),
• general weakness and lack of energy (fatigue), headache, dizziness,
• rash, itching,
• increase in liver enzyme activity, which can be seen in blood test results.

Uncommon(may affect up to 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, which can increase the risk of bleeding),
• allergic reactions, including allergic skin reactions,
• liver problems (which can be seen in tests performed by your doctor),
• blood test results may show increased levels of bilirubin, liver enzymes, or platelet count,
• fainting,
• feeling unwell,
• rapid heartbeat,
• dry mouth,
• hives.

Rare(may affect up to 1 in 1,000 people):

• bleeding into the muscles,
• cholestasis (bile flow obstruction), liver inflammation, including liver cell damage,
• jaundice (yellowing of the skin and eyes),
• local swelling,
• collection of blood (hematoma) in the groin as a complication of cardiac catheterization, when a catheter is inserted into an artery in the leg (pseudoaneurysm).

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

• accumulation of eosinophils, a type of white blood cell, which can cause inflammation in the lungs (eosinophilic pneumonia).

Frequency not known(frequency cannot be estimated from the available data):

• kidney failure after severe bleeding,
• kidney bleeding, sometimes with blood in the urine, leading to kidney failure (nephropathy associated with anticoagulant therapy),
• increased pressure in the muscles of the legs and arms after bleeding, which can lead to pain, swelling, changes in sensation, numbness, or paralysis (compartment syndrome after bleeding).

Side effects in children and adolescents

Overall, the side effects seen in children and adolescents treated with ZARIXA were similar in type to those seen in adults and were mainly mild to moderate.
Side effects seen more frequently in children and adolescents:
Very common(may affect more than 1 in 10 people):

• headache,
• fever,
• nosebleeds, vomiting.

Common(may affect up to 1 in 10 people):

• rapid heartbeat,
• blood test results may show increased levels of bilirubin,
• thrombocytopenia (low platelet count),
• excessive menstrual bleeding.

Uncommon(may affect up to 1 in 100 people):

• blood test results may show increased levels of a subtype of bilirubin (direct bilirubin).

Reporting side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Department of Drug Monitoring, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych, Al. Jerozolimskie 181C, 02-222 Warszawa, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
By reporting side effects, you can help provide more information on the safety of this 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 which is stated on the carton after EXP. The expiry date refers to the last day of that month.
Do not store above 30°C.
Contents of the capsule:
The contents of the capsule are stable in water or apple puree for up to 4 hours.
Medicines should 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 15 mg or 20 mg of rivaroxaban.
• The other ingredients are: Contents of the 15 mg and 20 mg capsules: mannitol, sodium lauryl sulfate, magnesium stearate. See section 2 "ZARIXA contains sodium". Capsule shell 15 mg: gelatin, iron oxide yellow (E 172), iron oxide red (E 172). Capsule shell 20 mg: gelatin, iron oxide red (E 172) Black ink: shellac, propylene glycol, potassium hydroxide, iron oxide, black (E 172).

What ZARIXA looks like and contents of the pack

ZARIXA 15 mg hard capsules are size "3", yellow body and orange-red cap, and are filled with a white or almost white powder.
ZARIXA 20 mg hard capsules are size "3", orange-red body and cap, with a black imprint "20" on the body, and are filled with a white or almost white powder.
Zarixa 15 mg
HDPE container with a child-resistant closure with a PP 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 closure with a PP 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
To obtain further information on this medicine, 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]

Date of last revision of the leaflet: