Xanirva

Package leaflet: Information for the patient

Xanirva, 15 mg, hard capsules
Xanirva, 20 mg, hard capsules
Rivaroxaban
Read the entire leaflet 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 a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

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

1. What Xanirva is and what it is used for

Xanirva contains the active substance rivaroxaban and 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 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 the recurrence of blood clots in the blood vessels of the legs and/or lungs.

Xanirva is used in children and adolescents under 18 years of age and with body weight of 30 kg or more to:

• treat blood clots and prevent the recurrence of blood clots in veins or in blood vessels of the lungs, after at least 5 days of initial treatment with injectable medicines used to treat blood clots.

Xanirva 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 Xanirva

When not to take Xanirva:

• 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 medicines that prevent blood clots (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 a liver disease that leads to an increased risk of bleeding;
• if the patient is pregnant or breastfeeding. Xanirva must not be used and the doctor must be informed if the patient suspects any of the above circumstances apply.

Warnings and precautions
Before starting Xanirva, consult a doctor or pharmacist.
When to exercise particular caution when taking Xanirva

• 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, as kidney function may affect the amount of medicine acting in the patient's body;
  • taking other medicines that prevent blood clots (e.g. warfarin, edoxaban, dabigatran 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 Xanirva");
  • 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 stomach and intestines or oesophagitis (throat and oesophagus), e.g. due to gastro-oesophageal reflux disease (backflow of stomach acid into the oesophagus) or tumours located in the stomach, intestines, genital or urinary system;
  • blood vessel disease in the back of the eyeball (retinopathy);
  • lung disease in which bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding;
• in patients with prosthetic heart valves;
• in patients with antiphospholipid syndrome (immune system disorders causing increased risk of blood clots). The doctor should be informed and may decide to change treatment if necessary;
• if the patient has abnormal blood pressure or if surgery or other treatment to remove a blood clot from the lungs is planned.

If the patient suspects that any of the above applies, they should inform the doctor
before taking Xanirva. The doctor will decide whether to use this medicine and whether the patient
should be placed under particularly close observation.
If the patient is to undergo surgery:

• it is very important to take Xanirva exactly at the times prescribed by the treating doctor, both before and after surgery;
• if during surgery catheterisation or lumbar puncture of the spine is planned (e.g. for epidural or spinal anaesthesia or for pain relief):
  • it is very important to take Xanirva exactly at the times prescribed by the treating doctor, both before and after the puncture or catheter removal;
  • the doctor must be informed immediately if, after the anaesthesia ends, numbness or weakness in the legs, or disturbances in bowel or bladder function occur, as immediate treatment may be necessary.

Children and adolescents
Xanirva 15 mg capsules are not recommended for children weighing less than 30 kg.
Xanirva 20 mg capsules are not recommended for children weighing less than 50 kg.
There is insufficient data on the use of rivaroxaban in children and adolescents for the indications approved in adults.
Xanirva and 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 the patient is taking:
  • certain antifungal medicines (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 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);
  • 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 the patient suspects that any of the above applies, they should inform the doctor
before using Xanirva, as the effect of Xanirva may be enhanced when taken together with the above-mentioned medicines. 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 stomach or duodenal ulcer, preventive treatment for peptic ulcer disease may be prescribed.

• 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, an antibiotic.

If the patient suspects that any of the above applies, they should inform the doctor
before using Xanirva, as the effect of Xanirva may be reduced when taken together with the above-mentioned medicines. The doctor will decide whether to use Xanirva and whether the patient should be placed under particularly close observation.
Pregnancy and breastfeeding
Do not use Xanirva if the patient is 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 Xanirva. If the patient becomes pregnant while taking Xanirva, she must inform the doctor immediately, who will decide on further management.
Driving and operating machinery
Xanirva 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.
Xanirva 15 mg and 20 mg contain monohydrate lactose (a type of sugar) and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.
The medicine contains less than 1 mmol of sodium (23 mg) per capsule, which means it is essentially "sodium-free".

3. How to take Xanirva

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Xanirva 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 methods of taking Xanirva with their doctor. The contents of the capsule may be 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 administer the contents of the Xanirva capsule through 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 Xanirva capsule once daily. If the patient has kidney problems, the dose may be reduced to one 15 mg Xanirva capsule once daily.

If a 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 Xanirva capsule once daily (or one 10 mg Xanirva capsule once daily in case of kidney 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 Xanirva capsule twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one 20 mg Xanirva 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 Xanirva capsule once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one 15 mg Xanirva capsule once daily, if the risk of bleeding is greater than the risk of further blood clots.

Children and adolescents
The dose of Xanirva depends on body weight and will be calculated by the doctor.

• The recommended dose for children and adolescents with body weight from 30 kg to below 50 kg is one 15 mg Xanirva capsule once daily.
• The recommended dose for children and adolescents with body weight of 50 kg or more is one 20 mg Xanirva capsule once daily.

Each dose of Xanirva 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 Xanirva is based on body weight, so it is important to attend scheduled doctor's appointments, as dose adjustments may be needed due to changes in weight.
Never adjust the dose of Xanirva on your own. If necessary, your doctor will adjust the dose.
Do not scatter the capsule contents to obtain a partial dose. If a lower dose is required, another medicine containing rivaroxaban in the form of granules for oral suspension should be used.
For children and adolescents who cannot swallow the capsules whole, a medicine containing rivaroxaban in the form of granules for oral suspension should be used.
If the oral suspension is not available, the contents of the Xanirva capsule may be scattered and mixed with water or apple puree immediately before administration. After consuming this mixture, a meal should be eaten. If necessary, the doctor may also administer the scattered contents of the Xanirva capsule through a gastric tube.

If a dose is vomited or spat out

• Less than 30 minutes after taking Xanirva, take a new dose.
• More than 30 minutes after taking Xanirva, do not take another dose. In this case, take the next dose of Xanirva at the usual time.

Contact your doctor if vomiting or spitting out the dose occurs repeatedly after taking Xanirva.

When to take Xanirva
Take the capsule(s) every day until your 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.
Your doctor will decide how long treatment should continue.
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, Xanirva should be taken as directed by your doctor.

Taking more Xanirva than prescribed
If a patient takes more Xanirva than prescribed, they should contact their doctor immediately. Taking too much Xanirva increases the risk of bleeding.

Missed dose

• 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 together to ensure a total of two capsules (30 mg) are taken in one day. The next day, resume taking one 15 mg capsule twice daily.

Stopping Xanirva treatment
Do not stop taking Xanirva without first consulting your doctor, as Xanirva 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 experiences them.
As with other medicines with a similar mechanism of action reducing blood clot formation, Xanirva may cause bleeding, which may 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 in an adult or child:
Signs of bleeding:

• intracranial or cerebral haemorrhage (symptoms may include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness and neck stiffness. A serious, acute medical emergency. Seek immediate medical help!).
• prolonged or heavy 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 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.
• These adverse reactions are very rare (may occur in less than 1 in 10,000 people).

Signs of serious allergic reaction:

• swelling of the face, lips, oral cavity, 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 less than 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)

• decreased number of red blood cells, which may cause skin pallor 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
• ocular haemorrhage (including bleeding from the sclera of the eye)
• bleeding into tissues or body cavities (hematoma, bruising)
• presence of blood in sputum during coughing (hemoptysis)
• skin bleeding or subcutaneous bleeding
• postoperative bleeding
• 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, diarrhea
• low blood pressure (symptoms may include dizziness or fainting upon standing)
• general loss of strength and energy (weakness, fatigue), headache, dizziness
• rash, skin itching
• increased activity of certain liver enzymes, which may be evident in blood test results.

Uncommon (may occur in 1 in 100 people)

• intracranial or cerebral haemorrhage (see above signs of bleeding)
• joint bleeding causing pain and swelling
• thrombocytopenia (low platelet count, 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
• dry mouth
• urticaria

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

• muscle bleeding
• 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 (cannot be estimated from available data)

• kidney failure following severe bleeding
• kidney bleeding, sometimes with 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)

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 that help in blood clotting)
• heavy menstrual bleeding

Uncommon (may occur in 1 in 100 people)

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

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, consult your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions 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 By reporting adverse reactions, additional information on the safety of the medicine can be collected. Adverse reactions may also be reported to the marketing authorization holder or its representative in Poland.

5. How to store Xanirva

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after: EXP. The expiry date refers to the last day of the stated month.
PVC/PVDC/Aluminium blisters: Store below 30°C.
Keep in the original packaging to protect from moisture.
OPA/Aluminium/PVC/Aluminium blisters: No special storage conditions apply.
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 Xanirva contains

• The active substance is rivaroxaban. Each capsule contains 15 mg or 20 mg of rivaroxaban.
• The other ingredients are: capsule contents: monohydrate lactose, microcrystalline cellulose, sodium croscarmellose, hypromellose, sodium lauryl sulfate, magnesium stearate. capsule shell: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172).

What Xanirva looks like and contents of the pack
Xanirva 15 mg: light brown, opaque capsules filled with white or almost white powder, size "1" (approximately 19 mm in length).
Xanirva 20 mg: dark brown, opaque capsules filled with white or almost white powder, size "0" (approximately 22 mm in length).
The hard capsules are packed in blisters made of PVC/PVDC/Aluminum or OPA/Aluminum/PVC/Aluminum foil, and cardboard boxes.
Xanirva 15 mg: available in packs of 14, 28, 30, 42, 98 or 100 hard capsules.
Xanirva 20 mg: available in packs of 14, 28, 30, 98 or 100 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130, Dolní Měcholupy
102 37 Prague 10
Czech Republic

Importer
Zentiva SA
B-dul Theodor Pallady no. 50, Sector 3
Bucharest 032266, Romania
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola PLA3000, Malta

This medicinal product is authorised for sale in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Czech Republic, Estonia, Latvia, Poland, Romania, Slovakia, United Kingdom (Northern Ireland):
Xanirva

For further information, please contact the local representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel. (22) 375 92 00