AXALTRA

Patient Information Leaflet

Axaltra 10 mg, coated tablets
Rivaroxaban
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 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 Axaltra is and what it is used for
2. What you need to know before you take Axaltra
3. How to take Axaltra
4. Possible side effects
5. How to store Axaltra
6. Contents of the pack and other information

1. What Axaltra is and what it is used for

Axaltra contains the active substance rivaroxaban and is used in adults to:
‐ prevent blood clots in the veins after hip or knee replacement surgery. Your doctor has prescribed this medicine because your risk of developing blood clots is increased after surgery.
‐ 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.

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 affecting an organ that increases the risk of
severe bleeding (e.g. stomach ulcer, trauma or bleeding in 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 patency of a venous or arterial catheter
- if the patient has a liver disease that increases the risk of bleeding
- if the patient is pregnant or breastfeeding

Do not use Axaltra and inform your doctor if you suspect any of the above-mentioned conditions.

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

When to exercise special caution when taking Axaltra
- if the patient has an increased risk of bleeding, such as in the following conditions:

• moderate or severe kidney disease, as kidney function may affect the amount of medicine acting in the patient's body
• if the patient is taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparine), except when switching anticoagulant therapy or if heparin is administered to maintain patency of a venous or arterial catheter (see section "Other medicines and Axaltra")
• bleeding disorders
• very high blood pressure that does not decrease despite medication
• stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestines and stomach or oesophagitis (throat and oesophagus), e.g. due to gastro-oesophageal reflux disease (acid reflux 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 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 abnormal blood pressure or if surgery or other treatment to remove a pulmonary clot is planned.

If you suspect any of the above conditions, inform your doctor
before taking Axaltra. The doctor will decide whether to use this medicine and whether the patient
should be placed under particularly close observation.

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

• strictly follow the doctor's instructions regarding the timing of taking Axaltra
• immediately inform the doctor if, after the anaesthesia ends, the patient experiences: numbness or weakness in the lower limbs, disturbances in bowel movements or bladder function, as immediate treatment will be necessary.

Children and adolescents
Axaltra 10 mg tablets are not recommended for patients under 18 years of age. There is insufficient data on the use of this medicine in children and adolescents.

Other medicines and Axaltra
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or 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 antibiotics (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 antidepressants (selective serotonin reuptake inhibitors (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI))

If you suspect any of the above conditions, inform your 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 should be placed under particularly close observation.

If the doctor considers that the patient has an increased risk of developing stomach or duodenal ulcers, 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 you suspect any of the above conditions, inform your 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 should be placed under particularly close observation.

Pregnancy and breastfeeding
Do not use Axaltra if you are 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 pregnancy occurs while taking this medicine, inform your doctor immediately. The doctor will decide on further management.

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 bicycles, or operate tools or machinery.

Axaltra contains lactose 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 tablet, meaning the medicine is considered "sodium-free".

3. How to take Axaltra

This medicine should always be taken exactly as your doctor has instructed. If you are unsure,
contact your doctor or pharmacist.
How many tablets to take
‐ to prevent the formation of blood clots in the veins following hip or knee replacement surgery
The recommended dose is one tablet of Axaltra 10 mg taken once daily.
‐ for the treatment of blood clots in the leg veins, blood clots in the blood vessels of the lungs,
and to prevent recurrence of blood clots.
After at least 6 months of treatment for blood clots, the recommended dose is one tablet of 10 mg once
daily or one tablet of 20 mg once daily. Your doctor has prescribed you Axaltra 10 mg once daily.
Swallow the tablet whole, preferably with water.
Axaltra may be taken with or without food.
If you have difficulty swallowing the whole tablet, talk to your doctor about other ways of taking Axaltra.
The tablet can be crushed and mixed with water or apple puree immediately before administration.
If necessary, your doctor may administer crushed Axaltra tablets through a gastric tube.
When to take Axaltra
Take one tablet each 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.
To prevent blood clots in the leg veins after hip or knee replacement surgery:
The first tablet should be taken between 6 and 10 hours after surgery.
For patients undergoing major hip surgery, treatment usually lasts 5 weeks.
For patients undergoing major knee surgery, treatment usually lasts 2 weeks.
Taking more Axaltra than recommended
If you take more Axaltra than prescribed, contact your doctor immediately. Taking too high a dose of Axaltra increases the risk of bleeding.
If you forget to take Axaltra
If you forget to take a dose, take the tablet as soon as you remember. Take the next tablet the following day, and then continue taking the tablets as usual, once daily.
Do not take a double dose to make up for a missed tablet.
Stopping Axaltra
Do not stop taking Axaltra without first talking to your doctor, as Axaltra helps prevent a serious condition.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, Axaltra may cause adverse reactions, although not everyone experiences them.
As with other medicines with a similar anticoagulant effect, Axaltra 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 must immediately inform your doctor if any of the following adverse reactions occur:

• Signs of bleeding – intracranial bleeding or bleeding within the skull (symptoms may include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness and neck stiffness. This is a serious, acute medical emergency. Immediate medical assistance must be sought!).

– prolonged or excessive bleeding
– unusual weakness, fatigue, pallor, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina pectoris
Your doctor may decide that close monitoring of the patient or a change in treatment approach 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 and systemic disorders.
  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 hypersensitivity 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
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
– gastrointestinal bleeding or intestinal bleeding, genitourinary bleeding (including blood in urine and severe menstrual bleeding), nosebleeds, gum bleeding
– ocular bleeding (including bleeding from the conjunctiva of the eye)
– bleeding into tissues or body cavities (hematoma, bruising)
– presence of blood in sputum (hemoptysis) during coughing
– 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 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)
– intracranial bleeding or bleeding within the skull (see signs of bleeding above)
– joint bleeding 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 up to 1 in 1,000 people)
– muscle bleeding
– cholestasis (bile stasis), hepatitis including liver cell damage
– yellowing of the skin and eyes (jaundice)
– localized swelling
– accumulation of blood (hematoma) in the groin as a complication of cardiac catheterization procedure, 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 granulocytic white 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 urine, leading to impaired kidney function (drug-induced anticoagulant-related nephropathy)
– 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 reactions occur, including any not listed in this leaflet, you should inform your doctor, pharmacist or nurse. 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 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 the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and blister after: EXP. The expiry date refers to the last day of the stated month.
No special storage instructions apply.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Axaltra contains
‐ The active substance is rivaroxaban. One coated tablet contains 10 mg of rivaroxaban.
‐ Other ingredients are:
tablet core: sodium lauryl sulfate, lactose, poloxamer 188, microcrystalline cellulose type 105,
microcrystalline cellulose type 102, sodium croscarmellose, magnesium stearate, colloidal silicon dioxide, anhydrous; 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 10 mg, coated tablets are light red, round, biconvex tablets, printed with the number "10" on one side and smooth on the other.
The tablet diameter is approximately 8.6 mm ± 0.2 mm.
Available in blister packs within cardboard boxes containing 5, 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 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]