Indifaxa

Package leaflet: Information for the user

INDIFAXA 10 mg film-coated tablets

Rivaroxaban
“Generic medicine”
Please read 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What INDIFAXA is and what it is used for

2. What you need to know before taking INDIFAXA

3. How to take INDIFAXA

4. Possible side effects

5. How to store INDIFAXA

6. Contents of the pack and other information

7. What is INDIFAXA and what is it used for

INDIFAXA contains the active substance rivaroxaban and is used in adults for:

• Preventing blood clots in the veins after hip or knee replacement surgery. Your doctor has prescribed this medicine because, after surgery, there is an increased risk of blood clots forming.
• Treating blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and preventing recurrence of blood clots in the veins of the legs and/or lungs.

INDIFAXA belongs to a group of medicines called antithrombotic agents. Its action is due to inhibition of clotting factor (factor Xa), thereby reducing the tendency of blood to form clots.

2. What you need to know before taking INDIFAXA

Do not take INDIFAXA

• If you are allergic to rivaroxaban or to any of the other ingredients of this medicine (listed in section 6)
• If you have excessive bleeding (bleeding)
• If you have a disease or condition in any part of the body that increases the risk of serious bleeding (e.g. stomach ulcers, wounds or bleeding in the brain, recent brain or eye surgery)
• If you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when switching anticoagulant therapy or when receiving heparin through a venous or arterial catheter to keep it open
• If you have a liver disease that increases the risk of bleeding
• During pregnancy or breastfeeding

Do not take INDIFAXA and inform your doctor if any of the conditions described above apply to you.
Warnings and precautions
Talk to your doctor or pharmacist before taking INDIFAXA.
Be especially careful with INDIFAXA

• If you have a high risk of bleeding, which may occur in situations such as:
• Moderate or severe kidney disease, because kidney function may affect the amount of active medicine in your body
• If you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), when switching anticoagulant therapy, or while receiving heparin through a venous or arterial catheter to keep it open (see section “Other medicines and INDIFAXA”)
• Coagulation disorders
• Very high blood pressure not controlled with medicines
• Stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestine or stomach, or inflammation of the oesophagus, such as that caused by gastroesophageal reflux disease (a condition in which stomach acid flows back into the oesophagus), or tumours in the stomach, intestine, genital tract or urinary tract
• A blood vessel disorder in the back of the eye (retinopathy)
• A lung disease with dilated bronchi filled with pus (bronchiectasis), or a history of bleeding from the lungs
• If you have a prosthetic heart valve
• If you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether a change in therapy is needed
• If your doctor finds that your blood pressure is unstable or if another treatment or surgical procedure to remove blood clots from the lungs is planned.

If any of the conditions described above apply to you, inform your doctor before taking INDIFAXA. The doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.
If you are scheduled for surgery

• It is very important to take INDIFAXA before and after surgery exactly as directed by your doctor.
• If the surgical procedure involves the use of a catheter or an injection into the spine (e.g. for epidural or spinal anaesthesia for pain relief):
• It is very important to take INDIFAXA exactly as directed by your doctor
• Inform your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after the anaesthesia, as urgent action may be required.

Children and adolescents
INDIFAXA is not recommended for patients under 18 years of age.
There is insufficient information on its use in children and adolescents.
Other medicines and INDIFAXA
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those without a prescription.

• If you are taking
• Certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless applied only to the skin
• Ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces excess cortisol)
• Certain antibiotics for bacterial infections (e.g. clarithromycin, erythromycin)
• Certain antiviral medicines for HIV/AIDS (e.g. ritonavir)
• Other medicines used to inhibit blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin and acenocoumarol)
• Anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid)
• Dronedarone, a medicine used in the treatment of atrial fibrillation
• Certain antidepressants (selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs))

If any of the conditions described above apply to you, inform your doctor before taking INDIFAXA, because the effect of INDIFAXA may be enhanced. The doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.
If your doctor believes you have an increased risk of developing stomach or intestinal ulcers, they may prescribe preventive ulcer treatment.

• If you are taking
• Certain medicines for epilepsy (phenytoin, carbamazepine, phenobarbital)
• St John's wort (Hypericum perforatum), a herbal remedy for depression
• Rifampicin, an antibiotic

If any of the conditions described above apply to you, inform your doctor before taking INDIFAXA, because the effect of INDIFAXA may be reduced. The doctor will decide whether you should be treated with INDIFAXA and whether you need to be closely monitored.
Pregnancy and breastfeeding
Do not take INDIFAXA during pregnancy or breastfeeding. If you could become pregnant, use a reliable method of contraception while taking INDIFAXA. If you become pregnant while taking this medicine, inform your doctor immediately, who will decide how to proceed with treatment.
Driving and using machines
INDIFAXA may cause dizziness (a common side effect) and fainting (an uncommon side effect) – see section 4, “Possible side effects”. If you experience these symptoms, do not drive or operate machinery.
INDIFAXA contains: lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take INDIFAXA
   Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.

What dose to take:

• To prevent blood clots in the veins after hip or knee replacement surgery, the recommended dose is one 10 mg tablet of INDIFAXA once daily.
• To treat blood clots in the veins of the legs and in the blood vessels of the lungs and to prevent recurrence of clots, after at least 6 months of treatment for blood clots, the recommended dose is one 10 mg tablet once daily or one 20 mg tablet once daily. Your doctor has prescribed you INDIFAXA 10 mg once daily.

Swallow the tablet preferably with some water.
INDIFAXA 10 mg can be taken regardless of meals.
If you have difficulty swallowing the tablet whole, ask your doctor how to take INDIFAXA in another way. The tablet may be crushed and mixed with water or apple puree immediately before taking.
If necessary, your doctor may administer crushed INDIFAXA tablets via a tube inserted into the stomach.
When to take INDIFAXA
Take the tablet every day until your doctor tells you to stop.
Try to take the tablets at the same time each day, to help you remember.
Your doctor will decide how long your treatment should continue.
To prevent blood clots in the veins after hip or knee replacement surgery, take the first tablet 6–10 hours after surgery.
If you have had major hip surgery, you will generally need to take the tablets for 5 weeks.
If you have had major knee surgery, you will generally need to take the tablets for 2 weeks.
If you take more INDIFAXA than you should
Contact your doctor immediately if you have taken too many INDIFAXA tablets. If you have taken an excessive amount of INDIFAXA, your risk of bleeding increases.
If you forget to take INDIFAXA
If you forget a dose, take it as soon as you remember. Take the next tablet the following day and continue with one tablet per day as before.
Do not take a double dose to make up for a forgotten tablet.
If you stop taking INDIFAXA
Do not stop taking INDIFAXA without first talking to your doctor, as INDIFAXA helps prevent a serious condition.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Like other similar medicines used to reduce blood clot formation, INDIFAXA can cause bleeding which may potentially be life-threatening. Severe bleeding can lead to a sudden drop in blood pressure (shock). In some cases, bleeding may not be obvious.
Tell your doctor immediately if you notice any of the following side effects:

Signs of bleeding

• Bleeding in the brain or skull (symptoms may include headache, weakness on one side of the body, vomiting, seizures, reduced level of consciousness, and neck stiffness. A 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 pectoris, which may be signs of bleeding. Your doctor may decide to monitor you closely or change your treatment.

Signs of serious skin reactions

• Widespread and severe rash, blisters or mucosal lesions, for example in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• A drug reaction causing rash, fever, internal organ inflammation, blood abnormalities, and systemic illness (DRESS syndrome). The frequency of these side effects is very rare (may affect up to 1 in 10,000 users).

Signs of serious allergic reactions

• Swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives; breathing difficulties; sudden drop in blood pressure. The frequencies of these side effects are very rare (anaphylactic reactions, including anaphylactic shock; may affect up to 1 in 10,000 users) and uncommon (angioedema and allergic edema; may affect up to 1 in 100 users).

Complete list of possible side effects
Common (may affect up to 1 in 10 users):

• Decrease in red blood cells, which may cause paleness, weakness or shortness of breath
• Bleeding in the stomach or intestines, urogenital bleeding (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding gums
• Bleeding in the eye (including bleeding in the white part of the eye)
• Bleeding into tissues or body cavities (hematoma, bruising)
• Coughing up blood
• Bleeding from or under the skin
• Bleeding after surgery
• Blood or fluid leakage from a surgical wound
• Swelling in limbs
• Limb pain
• Kidney dysfunction (can be detected by blood tests performed by your doctor)
• Fever
• Stomach ache, indigestion, feeling unwell, constipation, diarrhoea
• Low blood pressure (symptoms include dizziness or fainting when standing)
• General decrease in strength and energy (weakness, fatigue), headache, dizziness
• Rash, itching
• Increased levels of certain liver enzymes in blood tests

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

• Bleeding in the brain or within the skull (see above, signs of bleeding)
• Bleeding into a joint, causing pain and swelling
• Thrombocytopenia (reduced number of platelets, which are cells that help blood to clot)
• Allergic reactions, including skin allergic reactions
• Liver dysfunction (can be detected by blood tests performed by your doctor)
• Blood tests may show increased bilirubin, increased pancreatic or liver enzymes, or increased platelet count
• Fainting
• Feeling unwell, rapid heartbeat
• Dry mouth
• Hives

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

• Bleeding into a muscle
• Cholestasis (reduced bile flow, a substance produced by the liver), hepatitis including hepatocellular damage (liver inflammation including liver injury)
• Yellowing of the skin and eyes (jaundice)
• Localized swelling
• Formation of a blood collection (hematoma) in the groin as a complication of a heart procedure involving insertion of a catheter into the leg artery (pseudoaneurysm)

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

• Accumulation of eosinophils, a type of granulocyte white blood cell causing lung inflammation (eosinophilic pneumonia)

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

• Increased pressure in the muscles of arms or legs after bleeding, causing pain, swelling, sensory changes, numbness or paralysis (compartment syndrome following bleeding)
• Renal bleeding sometimes with blood in the urine leading to kidney dysfunction (Anticoagulant-induced nephropathy)
• Kidney impairment following severe bleeding

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website: http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store INDIFAXA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on each blister after
Exp. The expiry date refers to the last day of that month.
No special storage precautions required.
Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What INDIFAXA contains

• The active substance is rivaroxaban. Each tablet contains 10 mg of rivaroxiban.
• The other components are: Tablet core: monohydrate lactose, microcrystalline cellulose, sodium croscarmellose, hypromellose, sodium lauryl sulfate, magnesium stearate. See section 2 “INDIFAXA contains lactose and sodium”. Tablet film coating: hypromellose, hydroxypropylcellulose, polyethylene glycol 8000, titanium dioxide (E171), red iron oxide (E172). Description of the appearance of INDIFAXA and contents of the pack The 10 mg film-coated tablets of INDIFAXA are round, biconvex, light pink in colour, with “10” engraved on one side.

The tablets are supplied in PVC/PVDC 90/Aluminum blisters in boxes containing 28 tablets.
Marketing Authorization Holder and Manufacturer
ERREKAPPA EUROTERAPICI S.P.A
Via Ciro Menotti, 1/A
20129 Milano
Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice, Poland

Patient Information Leaflet: Information for the user

INDIFAXA 15 mg film-coated tablets, 20 mg film-coated tablets

Rivaroxaban
“Generic medicine”
Please read 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 doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

---

1. What INDIFAXA is and what it is used for

INDIFAXA contains the active substance rivaroxaban and is used in adults for:

• Preventing the formation of blood clots in the brain (stroke) and in other blood vessels of the body if you have a type of irregular heartbeat called non-valvular atrial fibrillation.
• Treating blood clots in the veins of the legs (deep vein thrombosis) and in the blood vessels of the lungs (pulmonary embolism), and preventing the recurrence of blood clots in the blood vessels of the legs and/or lungs.

INDIFAXA is used in children and adolescents under 18 years of age and with body weight equal to or greater than 30 kg for:

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

INDIFAXA belongs to a group of medicines called antithrombotic agents. Its action is due to the inhibition of a clotting factor (factor Xa), thereby reducing the blood’s tendency to form clots.

---

2. What you need to know before taking INDIFAXA

Do not take INDIFAXA

• If you are allergic to rivaroxaban or to any of the other ingredients of this medicine (listed in section 6)
• If you have excessive bleeding (bleeding)
• If you have a disease or condition in any part of the body that increases the risk of serious bleeding (e.g. stomach ulcers, wounds or bleeding in the brain, recent surgery on the brain or eyes)
• If you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when switching anticoagulant therapy or when receiving heparin through a venous or arterial catheter to keep it open
• If you have a liver disease that increases the risk of bleeding
• During pregnancy or breastfeeding

Do not take INDIFAXA and inform your doctor if any of the conditions described above apply to you.

---

Warnings and precautions

Talk to your doctor or pharmacist before taking INDIFAXA.

Be especially careful with INDIFAXA

• If you have an increased risk of bleeding, such as in the following cases:
  • Severe kidney disease, because kidney function may affect the amount of active medicine in your body
  • If you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), if you are switching anticoagulant therapy, or while receiving heparin through a venous or arterial catheter to keep it open (see section “Other medicines and INDIFAXA”)
  • Coagulation disorders
  • Very high blood pressure, uncontrolled by medicines
  • Stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestine or stomach, or inflammation of the oesophagus, such as that caused by gastro-oesophageal reflux disease (a condition in which stomach acid flows back into the oesophagus), or tumours located in the stomach, intestine, genital tract or urinary tract
  • A blood vessel disorder in the back of the eye (retinopathy)
  • A lung disease with dilated bronchi filled with pus (bronchiectasis), or a history of bleeding from the lungs
  • If you have a prosthetic heart valve
  • If you know you have a condition called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor, who will decide whether therapy needs to be changed
  • If your doctor finds your blood pressure is unstable or if another treatment or surgical procedure to remove blood clots from the lungs is planned

If any of the conditions described above apply to you, inform your doctor before taking INDIFAXA. Your doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored.

---

If you are scheduled for surgery

• It is very important to take INDIFAXA before and after surgery exactly as directed by your doctor.
• If the surgery involves the use of a catheter or an injection into the spine (e.g. for epidural or spinal anaesthesia for pain relief):
  • It is very important to take INDIFAXA before and after the injection or removal of the catheter exactly as directed by your doctor
  • Inform your doctor immediately if you experience numbness or weakness in your legs or bowel or bladder problems after the anaesthesia, as urgent intervention may be required.

---

Children and adolescents

INDIFAXA tablets are not recommended for children weighing less than 30 kg. There is insufficient information on the use of INDIFAXA in children and adolescents for the adult indications.

---

Other medicines and INDIFAXA

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

• If you are taking
  • Certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless applied only to the skin
  • Ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol)
  • Certain antibacterial medicines (e.g. clarithromycin, erythromycin)
  • Certain antiviral medicines for HIV/AIDS (e.g. ritonavir)
  • Other medicines used to inhibit blood clotting (e.g. enoxaparin, clopidogrel, or vitamin K antagonists such as warfarin and acenocoumarol)
  • Anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid)
  • Dronedarone, a medicine used to treat atrial fibrillation
  • Certain medicines for depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs))

If any of the conditions described above apply to you, inform your doctor before taking INDIFAXA, because the effect of INDIFAXA may be enhanced. Your doctor will decide whether you should be treated with this medicine and whether you need to be closely monitored. If your doctor believes you have an increased risk of developing stomach or intestinal ulcers, they may prescribe preventive treatment for ulcers.

• If you are taking
  • Certain antiepileptic medicines (phenytoin, carbamazepine, phenobarbital)
  • St John's wort (Hypericum perforatum), a herbal remedy for depression
  • Rifampicin, an antibiotic

If any of the conditions described above apply to you, inform your doctor before taking INDIFAXA, as the effect of INDIFAXA may be reduced. Your doctor will decide whether you should be treated with INDIFAXA and whether you need to be closely monitored.

---

Pregnancy and breastfeeding

Do not take INDIFAXA during pregnancy or breastfeeding. If there is a possibility you could become pregnant, use a reliable method of contraception while taking INDIFAXA. If you become pregnant while taking this medicine, inform your doctor immediately. Your doctor will decide how to proceed with treatment.

---

Driving and using machines

INDIFAXA may cause dizziness (a common side effect) and fainting (an uncommon side effect) – see section 4, “Possible side effects”. If you experience these symptoms, do not drive, ride a bicycle, or use tools or machinery.

---

INDIFAXA contains: lactose and sodium

If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take INDIFAXA

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Swallow the tablet or tablets with some water.
Take INDIFAXA with a meal.
If you have difficulty swallowing the tablet whole, ask your doctor how to take INDIFAXA in another way. The tablet may be crushed and mixed with water or apple puree immediately before administration. The mixture should be taken immediately followed by food.
If necessary, your doctor may administer crushed INDIFAXA tablets through a tube inserted into the stomach.

What dose to take
Adults

• To prevent blood clots in the brain (stroke) and in other blood vessels in the body, the recommended dose is one 20 mg tablet of INDIFAXA once daily. If you have kidney problems, the dose may be reduced to one 15 mg tablet of INDIFAXA once daily.

If you need to undergo a procedure to treat blocked blood vessels in your heart (called PCI – Percutaneous Coronary Intervention with stent placement), there is limited evidence supporting dose reduction to one 15 mg tablet of INDIFAXA once daily (or one 10 mg tablet of INDIFAXA if your kidneys do not function properly), in addition to an antiplatelet medicine such as clopidogrel.

• To treat blood clots in the veins of the legs and in the blood vessels of the lungs, and to prevent recurrence of clots, the recommended dose is one 15 mg tablet of INDIFAXA twice daily for the first 3 weeks. After 3 weeks, the recommended dose is one 20 mg tablet of INDIFAXA once daily. After at least 6 months of treatment for blood clots, your doctor may decide to continue treatment with either one 10 mg tablet once daily or one 20 mg tablet once daily.

If you have kidney problems and are taking one 20 mg tablet of INDIFAXA once daily, your doctor may decide to reduce the dose after 3 weeks to one 15 mg tablet of INDIFAXA once daily if the risk of bleeding is greater than the risk of developing a new blood clot.

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

• The recommended dose for children and adolescents with a body weight between 30 kg and 50 kg is one 15 mg tablet of INDIFAXA once daily.
• The recommended dose for children and adolescents with a body weight of 50 kg or more is one 20 mg tablet of INDIFAXA once daily.

Take each dose of INDIFAXA with a drink (e.g. water or juice) during a meal. Take the tablets at approximately the same time each day. Consider setting an alarm to remind you.
For parents or caregivers: please observe the child to ensure the full dose is taken.
Since the dose of INDIFAXA is based on body weight, it is important to attend scheduled doctor’s appointments, as the dose may need to be adjusted with changes in weight.
Never adjust the dose of INDIFAXA by yourself. If adjustment is needed, your doctor will do so.
Do not split the tablet in an attempt to divide the dose. If a lower dose is required, use an alternative formulation of rivaroxaban granules for oral suspension.
If the oral suspension is not available, the INDIFAXA tablet may be crushed and mixed with water or apple puree immediately before administration. Take food after taking this mixture. If necessary, your doctor may also administer crushed INDIFAXA tablets via a gastric tube.
For children and adolescents who cannot swallow whole tablets, use an alternative formulation of rivaroxaban granules for oral suspension.

If you spit out the dose or vomit

• If this happens less than 30 minutes after taking INDIFAXA, take a new dose.
• If this happens more than 30 minutes after taking INDIFAXA, do not take a new dose. In this case, take your next dose at the usual time.

Contact your doctor if you spit out the dose or vomit repeatedly after taking INDIFAXA.

When to take INDIFAXA
Take the tablet every day until your doctor tells you to stop.
Try to take the tablet(s) at the same time each day to help you remember.
Your doctor will decide how long your treatment should continue.
To prevent the formation of blood clots in the brain (stroke) and in other blood vessels of the body, if your heartbeat needs to be restored to normal through a procedure called cardioversion, take INDIFAXA exactly as your doctor instructed.

If you forget to take INDIFAXA
Adults, children and adolescents:

• If you are taking one 20 mg tablet or one 15 mg tablet once daily and you miss a dose, take it as soon as you remember. Do not take more than one tablet in one day to make up for the missed dose. Take the next tablet the following day and continue with one tablet once daily.

Adults:

• If you are taking one 15 mg tablet twice daily and you miss a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in one day. If you miss a dose, you may take two 15 mg tablets together to achieve a total of two tablets (30 mg) in one day. The following day, continue with one 15 mg tablet twice daily.

If you take more INDIFAXA than you should
Contact your doctor immediately if you have taken too many INDIFAXA tablets. If you have taken an excessive amount of INDIFAXA, your risk of bleeding increases.

If you stop taking INDIFAXA
Do not stop taking INDIFAXA without first talking to your doctor, as INDIFAXA treats serious conditions and prevents their occurrence.
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Like other similar medicines used to reduce blood clot formation, INDIFAXA can cause bleeding that may potentially be life-threatening. Massive bleeding can cause a sudden drop in blood pressure (shock). In some cases, bleeding may not be obvious.
Contact your doctor immediately if you notice any of the following side effects:
Signs of bleeding

• Bleeding in the brain or skull (symptoms may include headache, weakness on one side of the body, vomiting, seizures, reduced 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 pectoris. Your doctor may decide to monitor you closely or change your treatment.

Signs of severe skin reactions

• Widespread and intense rash, blisters or mucosal lesions, for example in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• A drug reaction causing rash, fever, internal organ inflammation, blood abnormalities, and systemic illness (DRESS syndrome). The frequency of these side effects is very rare (may affect up to 1 in 10,000 users).

Signs of severe allergic reactions

• Swelling of the face, lips, mouth, tongue or throat; difficulty swallowing; hives and breathing difficulties; sudden drop in blood pressure. The frequencies of severe allergic reactions are very rare (anaphylactic reactions, including anaphylactic shock; may affect up to 1 in 10,000 users) and uncommon (angioedema and allergic edema; may affect up to 1 in 100 users).

Complete list of possible side effects reported in adults, children and adolescents
Common (may affect up to 1 in 10 users):

• Decrease in red blood cells, which may cause paleness, weakness or shortness of breath
• Bleeding in the stomach or intestines, urogenital bleeding (including blood in urine and heavy menstrual bleeding), nosebleeds, bleeding gums
• Bleeding in the eye (including bleeding in the white part of the eye)
• Bleeding into tissues or body cavities (hematoma, bruising)
• Coughing up blood
• Bleeding from or under the skin
• Bleeding after surgery
• Blood or fluid leakage from surgical wound
• Swelling of limbs
• Limb pain
• Kidney dysfunction (can be detected by blood tests performed by your doctor)
• Fever
• Stomach ache, indigestion, feeling or state of malaise, constipation, diarrhea
• Low blood pressure (symptoms include dizziness or fainting when standing)
• General decrease in strength and energy (weakness, fatigue), headache, dizziness
• Rash, itching
• Increased liver enzymes in blood tests

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

• Bleeding in the brain or inside the skull (see above, signs of bleeding)
• Bleeding into a joint, causing pain and swelling
• Thrombocytopenia (reduced platelet count; platelets are the cells that allow blood to clot)
• Allergic reactions, including skin allergic reactions
• Liver dysfunction (can be detected by blood tests performed by your doctor)
• Blood tests may show increased bilirubin, increased pancreatic or liver enzymes, or increased platelet count
• Fainting
• Malaise
• Rapid heartbeat
• Dry mouth
• Hives

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

• Bleeding into a muscle
• Cholestasis (reduced bile flow, a substance produced by the liver), hepatitis including hepatocellular damage (liver inflammation including liver injury)
• Yellowing of the skin and eyes (jaundice)
• Localized swelling
• Formation of a blood collection (hematoma) in the groin as a complication of a heart procedure involving insertion of a catheter into the leg artery (pseudoaneurysm)

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

• Accumulation of eosinophils, a type of granulocyte white blood cell causing lung inflammation (eosinophilic pneumonia)

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

• Increased pressure in the muscles of arms or legs after bleeding, causing pain, swelling, sensory changes, numbness or paralysis (compartment syndrome after bleeding)
• Kidney bleeding sometimes with blood in urine leading to kidney dysfunction (anticoagulant-related nephropathy)
• Kidney failure after severe bleeding

Side effects in children and adolescents
In general, the side effects observed in children and adolescents treated with INDIFAXA have been similar to those observed in adults and have mainly been mild to moderate in severity.
Side effects observed 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)

• Increased heart rate
• Blood tests may show increased bilirubin (bile pigment)
• Thrombocytopenia (reduced platelet count; platelets are the cells that allow blood to clot)
• Heavy menstrual bleeding

Uncommon (may affect up to 1 in 100 people)

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/en/content/segnalazioni-reazioni-avverse. Reporting side effects helps provide more information on the safety of this medicine.

5 How to store INDIFAXA
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 and on each blister after Exp. The expiry date refers to the last day of that month.
No special storage precautions required.
Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What INDIFAXA contains

• The active substance is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.
• The other components are: Tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hypromellose, sodium lauryl sulfate, magnesium stearate. See section 2 “INDIFAXA contains lactose and sodium”.

Tablet coating: hypromellose, hydroxypropylcellulose, macrogol 8000,
titanium dioxide (E171), red iron oxide (E172).

Description of the appearance of INDIFAXA and contents of the pack
The film-coated tablets of INDIFAXA 15 mg are round, biconvex, pink in colour, with “15” engraved on one side.
The film-coated tablets of INDIFAXA 20 mg are round, biconvex, brown in colour, with “20” engraved on one side.
The film-coated tablets are supplied in PVC/PVDC 90/Aluminium blisters, in boxes containing 28 tablets.

Marketing Authorisation Holder and Manufacturer
ERREKAPPA EUROTERAPICI S.P.A
Via Ciro Menotti, 1/A
20129 Milano, Italy

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice, Poland