Package leaflet: Information for the patient

Axaltra, 15 mg, film-coated tablets
Axaltra, 20 mg, film-coated tablets
Rivaroxabanum
Please read this leaflet carefully before using the medicine because it contains
important information for the patient.

Keep this leaflet for future reference.
If you have any further questions, please consult 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 adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

What Axaltra is and what it is used for
Important information before taking Axaltra
How to take Axaltra
Possible side effects
How to store Axaltra
Contents of the pack and other information

1. What Axaltra is and what it is used for

Axaltra contains the active substance rivaroxaban.
Axaltra is used in adults to:
– prevent the formation of blood clots in the brain (stroke) and other blood vessels in the body in patients who have a type of irregular heart rhythm 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.

Axaltra 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.

Axaltra 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 using Axaltra

When not to take Axaltra
‐ 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, injury or bleeding into the brain, recent
surgery on the brain or eyes)
‐ if the patient is taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran,
apixaban or heparin), except when switching anticoagulant therapy or if heparin
is administered to maintain the patency of a catheter 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

Do not take Axaltra, and also inform your doctor if the patient suspects that any of the above circumstances apply.

Warnings and precautions
Before starting to take Axaltra, consult your doctor or pharmacist.

When to exercise particular caution when taking Axaltra
‐ 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 clotting (e.g. warfarin, dabigatran, apixaban or heparin), when switching anticoagulant therapy or when heparin is administered to maintain the patency of a catheter in a vein or artery (see section "Other medicines and Axaltra")
blood clotting disorders
very high blood pressure that does not decrease despite taking medication
diseases of the stomach or intestines that may cause bleeding, e.g. inflammation of the intestines and stomach or oesophagitis (inflammation of the 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 at the back of the eyeball (retinopathy)
lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding
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 a change in treatment is necessary
if the patient has been diagnosed with 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, they should inform the doctor
before taking Axaltra. The doctor will decide whether to use this medicine and whether the patient needs
to be placed under particularly close observation.

If the patient needs to undergo surgery
‐ strictly follow the doctor's instructions regarding the timing of taking Axaltra before or after surgery
‐ if during surgery catheterization or spinal puncture (e.g. for epidural or spinal anaesthesia or pain relief) is planned:

it is very important to take Axaltra before and after the puncture or removal of the catheter, as directed by the doctor
due to the need for special caution, the doctor should 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
Axaltra tablets are not recommended for children weighing less than 30 kg.
There is insufficient data on the use of Axaltra in children and adolescents for the indications approved for adults.

Other medicines and Axaltra
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, a condition 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 taking Axaltra, as the effect of Axaltra may be enhanced when taken together with the above-mentioned medicines. The doctor will decide whether to use this medicine and whether the patient needs to 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, they may prescribe 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, they should inform the doctor
before taking Axaltra, as the effect of Axaltra may be reduced when taken together with the above-mentioned medicines. The doctor will decide whether to use Axaltra and whether the patient needs to be placed under particularly close observation.

Pregnancy and breastfeeding
Do not take Axaltra 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 Axaltra. If the patient becomes pregnant while taking this medicine, she should inform her doctor immediately, who will decide on further treatment.

Driving and operating machinery
Axaltra 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.

Axaltra contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, they should contact their doctor before taking this medicine.
The medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to take Axaltra

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Axaltra 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 speak to their doctor about alternative ways of taking Axaltra. The tablet may be crushed and mixed with water or apple puree immediately before administration. A meal should be taken immediately after this mixture.
If necessary, a doctor may administer crushed Axaltra tablets via a gastric tube.

How many tablets to take

Adults – For the prevention of blood clots in the brain (stroke) and other blood vessels in the body:
The recommended dose is one 20 mg Axaltra tablet once daily. If the patient has kidney problems, the dose may be reduced to one 15 mg Axaltra tablet once daily.

If the patient requires a procedure to unblock blood vessels in the heart (called percutaneous coronary intervention – PCI with stent placement), there is limited evidence supporting dose reduction to one 15 mg Axaltra tablet once daily (or one 10 mg Axaltra tablet once daily in case of renal impairment), in combination with an antiplatelet medicine such as clopidogrel.

– For the treatment of blood clots in the veins of the legs, blood clots in the blood vessels of the lungs, and to prevent recurrence of blood clots:
The recommended dose is one 15 mg Axaltra tablet twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one 20 mg Axaltra 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 problems and is taking one 20 mg Axaltra tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one 15 mg Axaltra tablet once daily, if the risk of bleeding is greater than the risk of further blood clots.
Children and adolescents
The dose of Axaltra 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 below 50 kg: one 15 mg Axaltra tablet once daily.
– Recommended dose for children and adolescents with a body weight of 50 kg or more: one 20 mg Axaltra tablet once daily.
Each dose of Axaltra should be taken with a meal and with 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: observe the child to ensure they have taken the full dose.

The dose of Axaltra depends on body weight, so it is important to attend scheduled doctor’s appointments, as dose adjustments may be necessary due to changes in weight.
Never adjust the dose independently. If necessary, 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 Axaltra, namely granules for oral suspension, should be used.
For children and adolescents who are unable to swallow whole tablets, Axaltra granules for oral suspension should be used.
If the oral suspension is not available, the Axaltra tablet may be crushed and mixed with water or apple puree immediately before administration. A meal should be taken immediately after this mixture.
If necessary, the doctor may also administer the crushed tablet via a gastric tube.

If a dose is vomited or expelled

Within 30 minutes of taking Axaltra, take a new dose.
More than 30 minutes after taking Axaltra, do not take a new dose. In this case, take the next dose at the usual time. Contact your doctor if there are repeated episodes of vomiting or expelled doses after taking Axaltra.

When to take Axaltra
Take one tablet every day until your doctor decides to stop treatment.
It is best to take the tablet at the same time each day, as this makes it easier to remember.
Your doctor will decide how long treatment should continue.
For the prevention of blood clots in the brain (stroke) and other blood vessels in the body:
If heart rhythm needs to be restored by a procedure called cardioversion, Axaltra should be taken as directed by your doctor.

Missed dose of Axaltra

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 a dose was forgotten, the patient 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 Axaltra
If a patient has taken too many Axaltra tablets, contact a doctor immediately.
Taking too high a dose of Axaltra increases the risk of bleeding.

Stopping Axaltra treatment
Do not stop taking Axaltra without first discussing it with your doctor, as Axaltra helps prevent 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, Axaltra may cause adverse reactions, although not everyone experiences them.
As with other medicines with a similar mechanism of action that reduce blood clot formation, Axaltra can cause bleeding, which potentially 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.
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, 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 – widespread, acute skin rash, formation of blisters or mucosal lesions, e.g., in the mouth or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis) – Drug reaction causing rash, fever, internal organ inflammation, hematological and systemic disorders (DRESS syndrome). The frequency of these adverse reactions is very rare (occurring in up to 1 in 10,000 people).
Signs of serious allergic reactions – 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 up to 1 in 10,000 people) and uncommon (angioedema and allergic edema may occur in up to 1 in 100 people).

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 skin pallor 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 subconjunctival 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 (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 reduction 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 within 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 (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 determined from available data)
– Kidney failure following severe bleeding
– Bleeding in the kidneys, sometimes with blood in the urine, leading to impaired kidney function (anticoagulant-associated nephropathy)
– Increased pressure in the muscles of the 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
In general, adverse reactions observed in children and adolescents treated with Axaltra 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 up to 1 in 10 people)
– Rapid heartbeat
– Blood tests may show increased bilirubin levels (a bile pigment)
– Thrombocytopenia (low platelet count, blood cells that help in blood clotting)
– Excessive menstrual bleeding

Uncommon (may occur in up to 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 not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, 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 to provide more information on the safety of the medicine.

5. How to store Axaltra

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and blister pack after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the pack and other information

What Axaltra contains
‐ The active substance is rivaroxaban. One coated tablet contains 15 mg or 20 mg of
rivaroxaban.
‐ The other ingredients are:
tablet core: sodium lauryl sulfate, lactose, poloxamer 188, microcrystalline cellulose type 105,
microcrystalline cellulose type 102, sodium croscarmellose, magnesium stearate, colloidal anhydrous silica, see section 2 "Axaltra contains lactose and sodium"
tablet coating: hypromellose type 2910, titanium dioxide (E 171), macrogol 3350, iron oxide red (E 172)

What Axaltra looks like and contents of the pack
Axaltra 15 mg, coated tablets are red, round, biconvex tablets, embossed with the number "15" on one side and smooth on the other.
The tablet diameter is approximately 5.6 mm ± 0.2 mm.
They are available in blister packs within cardboard boxes containing 10, 14, 28, 30, 42, 50, 98 or 100 coated tablets.
Not all pack sizes may be marketed.

Axaltra 20 mg, coated tablets are reddish-brown, round, biconvex tablets, embossed with the number "20" on one side and smooth on the other.
The tablet diameter is approximately 6.6 mm ± 0.2 mm.
They are available in blister packs within cardboard boxes containing 10, 14, 28, 30, 98 or 100 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
+pharma arzneimittel gmbh
Hafnerstrasse 211
8054 Graz
Austria

Manufacturer
Rontis Hellas Medical and Pharmaceutical Products S.A.
P.O. Box 3012 Larisa Industrial Area
41004 Larisa
Greece
PharOS MT Ltd.
HF62X, Hal Far Industrial Estate
BBG3000 Birzebbuga
Malta
Genericon Pharma Gesellschaft m.b.H.
Hafnerstrasse 211
8054 Graz
Austria

This medicinal product is authorised for marketing in the European Economic Area under the following names:
Hungary Xabdu 2.5 mg, 10 mg, 15 mg, 20 mg film-coated tablets
Czech Republic Axaltra
Croatia Cloter 2.5 mg, 10 mg, 15 mg, 20 mg film-coated tablets
Poland Axaltra

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder in Poland:
+pharma Polska sp. z o.o.
ul. Podgórska 34
31-536 Kraków, Poland
tel.: +48 12 262 32 36
e-mail: [email protected]