Xerdoxo

Package leaflet: Information for the patient

Xerdoxo, 15 mg, film-coated tablets
Xerdoxo, 20 mg, film-coated tablets
Rivaroxabanum
Please read this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• 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

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

1. What Xerdoxo is and what it is used for

Xerdoxo contains the active substance rivaroxaban. Xerdoxo 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 veins of the legs and/or lungs.

Xerdoxo 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 to 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.

Xerdoxo belongs to a group of medicines called anticoagulants. It works by blocking a blood clotting factor (factor Xa), thereby reducing the tendency to form blood clots.

2. Important information before using Xerdoxo

When not to use Xerdoxo

• 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 the patency of a venous 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.

Do not use Xerdoxo and inform your doctor if the patient suspects that any of the above circumstances apply.

Warnings and precautions

Before starting to take Xerdoxo, consult a doctor or pharmacist.

When to exercise special caution when using Xerdoxo

• 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, etexilate dabigatran, apixaban or heparine) when switching anticoagulant therapy or when heparin is administered to maintain the patency of a venous or arterial catheter (see section "Xerdoxo with other medicines"),
• blood clotting disorders,
• very high blood pressure that does not decrease despite medication,
• stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestine 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 heart valve prostheses,
• 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 is scheduled for surgery or other treatment aimed at removing a blood clot from the lungs.

If the patient suspects that any of the above conditions apply, they should inform the doctor before using Xerdoxo. 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 taking Xerdoxo at a specific time before or after surgery,
• if during a surgical procedure the patient is scheduled to undergo a lumbar puncture or have a catheter inserted into the spine (e.g. for epidural or intrathecal anaesthesia or for pain relief):
• it is very important to take Xerdoxo before and after the puncture or catheter removal, as directed by the doctor,
• the patient should immediately inform the doctor if, after the anaesthesia has ended, symptoms such as numbness or weakness in the lower limbs, or disturbances in bowel or bladder function occur, as immediate treatment will then be necessary.

Children and adolescents

Xerdoxo tablets are not recommended for children weighing less than 30 kg. There is insufficient data on the use of Xerdoxo in children and adolescents for the indications approved for adults.

Xerdoxo 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 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 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 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-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 (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)).

If the patient suspects that any of the above conditions apply, they should inform the doctor before using Xerdoxo, as the effect of Xerdoxo 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 stomach or intestinal ulcers, they may prescribe treatment to prevent peptic 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, they should inform the doctor before using Xerdoxo, as the effect of Xerdoxo may be reduced. The doctor will decide whether to use Xerdoxo and whether the patient should be placed under particularly close observation.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant or is planning to have a baby, she should consult a doctor or pharmacist before using this medicine.

Do not use Xerdoxo 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 Xerdoxo. If the patient becomes pregnant while taking Xerdoxo, she should immediately inform the doctor, who will decide on further treatment.

Driving and using machines

Xerdoxo 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.

Xerdoxo contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning that the medicine is considered "sodium-free".

3. How to take Xerdoxo

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Xerdoxo should be taken with food.
The tablet(s) should be swallowed whole, preferably with water.
If a patient has difficulty swallowing the whole tablet, they should discuss alternative methods of taking Xerdoxo with their doctor. The tablet may be crushed and mixed with water or soft food such as apple puree immediately before administration. After taking this mixture, the patient should immediately eat a meal.
If necessary, a crushed Xerdoxo tablet may be administered through a gastric tube by a doctor.

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 Xerdoxo 20 mg tablet once daily. If the patient has kidney disease, the dose may be reduced to one Xerdoxo 15 mg tablet 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 Xerdoxo 15 mg tablet once daily (or one Xerdoxo 10 mg tablet 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 Xerdoxo 15 mg tablet twice daily for the first 3 weeks. For treatment beyond 3 weeks, the recommended dose is one Xerdoxo 20 mg 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 Xerdoxo 20 mg tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one Xerdoxo 15 mg tablet once daily, if the risk of bleeding is greater than the risk of developing further blood clots.

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

• Recommended dose for children and adolescents with a body weight of 30 kg to less than 50 kg is one Xerdoxo 15 mg tablet once daily.

• Recommended dose for children and adolescents with a body weight of 50 kg or more is one Xerdoxo 20 mg tablet once daily.
  Each dose of Xerdoxo should be taken with a meal, accompanied by 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: monitor the child to ensure they have taken the full dose.

The dose of Xerdoxo depends on body weight; therefore, it is important to attend scheduled appointments with the doctor, as dose adjustments may be necessary due to changes in weight.
Never adjust the dose independently. If needed, the doctor will adjust the dose.
Do not split the tablet to achieve a partial dose. If a lower dose is required, another formulation of rivaroxaban should be used – granules for oral suspension.
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 Xerdoxo tablet may be crushed and mixed with water or apple puree immediately before administration. After taking this mixture, the patient should immediately eat a meal. If necessary, the doctor may also administer the crushed tablet via a gastric tube.

If a dose is vomited or expelled

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

Contact your doctor if there are repeated instances of vomiting or expelling the dose after taking Xerdoxo.

When to take Xerdoxo
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 treatment should continue.

Prevention of blood clots in the brain (stroke) and other blood vessels in the body:
If restoration of normal heart rhythm is required via a cardioversion procedure, Xerdoxo should be taken as directed by your doctor.

Missed dose of Xerdoxo

• 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 forgot 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 Xerdoxo
If a patient takes more than the recommended dose of Xerdoxo, contact a doctor immediately. Taking too high a dose of Xerdoxo increases the risk of bleeding.

Stopping Xerdoxo treatment
Do not stop taking Xerdoxo without first consulting your doctor, as Xerdoxo 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 blood-thinning effect, Xerdoxo may cause bleeding, which could potentially 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 or a change in treatment is necessary.

Signs of severe skin reaction

• 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 (occurring in up to 1 in 10,000 patients).

Signs of severe allergic reaction

• Swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; urticaria and breathing difficulties; sudden drop in blood pressure. The frequency of severe allergic reaction 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 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 severe menstrual bleeding), nosebleeds, bleeding gums,
• 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 bleeding,
• Bleeding after surgery,
• Oozing of blood or fluid from the surgical wound,
• Swelling of limbs,
• 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 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 up to 1 in 100 people)

• Bleeding into the brain or inside 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,
• Dry mouth,
• Urticaria.

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 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 the urine, leading to the kidneys being unable to function properly (anticoagulant-related nephropathy),
• Increased pressure in the muscles of the 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 mainly 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, the blood 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 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, inform 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
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 Xerdoxo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "EXP". The expiry date refers to the last day of the stated month.
No special storage conditions apply for this medicine.
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 packaging and other information

What Xerdoxo 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, polyethylene glycol 8000, poloxamer 188, sodium lauryl sulfate, sodium croscarmellose, colloidal anhydrous silica, and sodium stearyl fumarate in the tablet core; and hypromellose 2910, polyethylene glycol 4000, titanium dioxide (E 171), iron oxide, red (E 172), and iron oxide, yellow (E 172) – only in 15 mg coated tablets – in the tablet coating. See section 2, "Xerdoxo contains sodium".

What Xerdoxo looks like and contents of the pack
15 mg:
Reddish-orange to brownish-orange, round, slightly biconvex coated tablets, embossed with the mark "15" on one side.
Dimensions: approximately 6.5 mm in diameter.
20 mg:
Pink to dark pink, round, slightly biconvex coated tablets, embossed with the mark "20" on one side.
Dimensions: approximately 7 mm in diameter.
15 mg:
Xerdoxo is available in cartons containing:

• calendar packs: 14, 28, or 42 coated tablets in blister packs.

A patient warning card is included with each medicine package.
20 mg:
Xerdoxo is available in cartons containing:

• calendar packs: 14, 28, or 42 coated tablets in blister packs.

A patient warning card is included with each medicine package.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

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
telephone: +48 22 573 75 00