Rivaroxaban Krka 2.5 mg film-coated tablets – patient leaflet, side effects, dosage

1. What <Invented name> is and what it is used for

You have been given <Invented name> because

• you have been diagnosed with an acute coronary syndrome (a group of conditions that includes heart attack and unstable angina, a severe type of chest pain) and have been shown to have had an increase in certain cardiac blood tests.

  <Invented name> reduces the risk in adults of having another heart attack or reduces the risk of dying from a disease related to your heart or your blood vessels. <Invented name> will not be given to you on its own. Your doctor will also tell you to take either:

  • acetylsalicylic acid or
  • acetylsalicylic acid plus clopidogrel or ticlopidine.

or

• you have been diagnosed with a high risk of getting a blood clot due to a coronary artery disease or peripheral artery disease which causes symptoms. <Invented name> reduces the risk in adults of getting blot clots (atherothrombotic events).

  <Invented name> will not be given to you on its own. Your doctor will also tell you to take acetylsalicylic acid.

  In some cases, if you get <Invented name> after a procedure to open a narrowed or closed artery of your leg to restore blood flow, your doctor may also prescribe clopidogrel for you to take in addition to acetylsalicylic acid for a short while.

<Invented name> contains the active substance rivaroxaban and belongs to a group of medicines called antithrombotic agents. It works by blocking a blood clotting factor (factor Xa) and thus reducing the tendency of the blood to form clots.

2. What you need to know before you take <Invented name>

Do not take <Invented name>

• if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6)
• if you are bleeding excessively
• if you have a disease or condition in an organ of the body that increases the risk of serious bleeding (e.g. stomach ulcer, injury or bleeding in the brain, recent surgery of the brain or eyes)
• if you are taking medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), except when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open
• if you have an acute coronary syndrome and previously had a bleeding or a blood clot in your brain (stroke)
• if you have coronary artery disease or peripheral artery disease and previously had a bleeding in your brain (stroke) or where there was a blockage of the small arteries providing blood to the brain’s deep tissues (lacunar stroke) or if you had a blood clot in your brain (ischaemic, non- lacunar stroke) in the previous month - if you have a liver disease which leads to an increased risk of bleeding - if you are pregnant or breast-feeding

Do not take <Invented name> and tell your doctor if any of these apply to you.

Warnings and precautions

Talk to your doctor or pharmacist before taking <Invented name>.

<Invented name> should not be used in combination with certain other medicines which reduce blood clotting such as prasugrel or ticagrelor other than acetylsalicylic acid and clopidogrel/ticlopidine.

Take special care with <Invented name>

• if you have an increased risk of bleeding, as could be the case in situations such as:

  • severe kidney disease, since your kidney function may affect the amount of medicine that works in your body
  • if you are taking other medicines to prevent blood clotting (e.g. warfarin, dabigatran, apixaban or heparin), when changing anticoagulant treatment or while getting heparin through a venous or arterial line to keep it open (see section “Other medicines and <Invented name>”)
  • bleeding disorders
  • very high blood pressure, not controlled by medical treatment • diseases of your stomach or bowel that might result in bleeding, e.g. inflammation of the bowels or stomach, or inflammation of the oesophagus (gullet), e.g. due to gastroesophageal reflux disease (disease where stomach acid goes upwards into the oesophagus) or tumours located in the stomach or bowels or genital tract or urinary tract

• a problem with the blood vessels in the back of your eyes (retinopathy) • a lung disease where your bronchi are widened and filled with pus (bronchiectasis), or previous bleeding from your lung
• you are older than 75 years
• you weigh less than 60 kg
• you have a coronary artery disease with severe symptomatic heart failure - if you have a prosthetic heart valve
• if you know that you have a disease called antiphospholipid syndrome (a disorder of the immune system that causes an increased risk of blood clots), tell your doctor who will decide if the treatment may need to be changed.

If any of the above apply to you, tell your doctor before you take <Invented name>. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.

If you need to have an operation

• it is very important to take <Invented name> before and after the operation exactly at the times you have been told by your doctor.

• If your operation involves a catheter or injection into your spinal column (e.g. for epidural or spinal anaesthesia or pain reduction):

  • it is very important to take <Invented name> before and after the injection or removal of the catheter exactly at the times you have been told by your doctor • tell your doctor immediately if you get numbness or weakness of your legs or problems with your bowel or bladder after the end of anaesthesia, because urgent care is necessary.

Children and adolescents

<Invented name> 2.5 mg tablets are not recommended for people under 18 years of age. There is not enough information on their use in children and adolescents.

Other medicines and <Invented name>

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

• If you are taking

  • some medicines for fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are only applied to the skin
  • ketoconazole tablets (used to treat Cushing’s syndrome - when the body produces an excess of cortisol)
  • some medicines for bacterial infections (e.g. clarithromycin, erythromycin) • some anti-viral medicines for HIV / AIDS (e.g. ritonavir)
  • other medicines to reduce blood clotting (e.g. enoxaparin, clopidogrel or vitamin K antagonists such as warfarin and acenocoumarol, prasugrel and ticagrelor (see section “Warnings and Precautions”))
  • anti-inflammatory and pain relieving medicines (e.g. naproxen or acetylsalicylic acid)
  • dronedarone, a medicine to treat abnormal heart beat

  • some medicines to treat depression (selective serotonin reuptake inhibitors (SSRIs)

    or serotonin norepinephrine reuptake inhibitors (SNRIs))

If any of the above apply to you, tell your doctor before taking <Invented name>, because the effect of <Invented name> may be increased. Your doctor will decide, if you should be treated with this medicine and if you should be kept under closer observation.

If your doctor thinks that you are at increased risk of developing stomach or bowel ulcers, he may also use a preventative ulcer treatment.

• If you are taking

  • some medicines for treatment of epilepsy (phenytoin, carbamazepine, phenobarbital)
  • St John’s Wort (Hypericum perforatum), a herbal product used for depression • rifampicin, an antibiotic

If any of the above apply to you, tell your doctor before taking <Invented name>, because the effect of <Invented name> may be reduced. Your doctor will decide, if you should be treated with <Invented name> and if you should be kept under closer observation.

Pregnancy and breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Do not take <Invented name> if you are pregnant or breast-feeding. If there is a chance that you could become pregnant, use a reliable contraceptive while you are taking <Invented name>. If you become pregnant while you are taking this medicine, tell your doctor immediately, who will decide how you should be treated.

Driving and using machines

<Invented name> may cause dizziness (common side effect) or fainting (uncommon side effect) (see section 4, ”Possible side effects”). You should not drive, ride a bicycle or use any tools or machines if you are affected by these symptoms.

<Invented name> contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ”sodium- free”.

3. How to take <Invented name>

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

How much to take

The recommended dose is one 2.5 mg tablet twice a day. Take <Invented name> around the same time every day (for example, one tablet in the morning and one in the evening). This medicine can be taken with or without food.

If you have difficulty swallowing the tablet whole, talk to your doctor about other ways to take <Invented name>. The tablet may be crushed and mixed with water or apple puree immediately before you take it.

If necessary, your doctor may also give you the crushed <Invented name> tablet through a stomach tube.

<Invented name> will not be given to you on its own.

Your doctor will also tell you to take acetylsalicylic acid. If you get <Invented name> after an acute coronary syndrome, your doctor may tell you to also take clopidogrel or ticlopidine. If you get <Invented name> after a procedure to open a narrowed or closed artery of your leg to restore blood flow, your doctor may also prescribe clopidogrel for you to take in addition to acetylsalicylic acid for a short while.

Your doctor will tell you how much of these to take (usually between 75 to 100 mg acetylsalicylic acid daily or a daily dose of 75 to 100 mg acetylsalicylic acid plus a daily dose of either 75 mg clopidogrel or a standard daily dose of ticlopidine).

When to start <Invented name>

Treatment with <Invented name> after an acute coronary syndrome should be started as soon as possible after stabilization of the acute coronary syndrome, at the earliest 24 hours after admission to hospital and at the time when parenteral (via injection) anticoagulation therapy would normally be stopped.

Your doctor will tell you when to start treatment with <Invented name> if you have been diagnosed with coronary artery disease or peripheral artery disease.

Your doctor will decide how long you must continue treatment.

If you take more <Invented name> than you should

Contact your doctor immediately if you have taken too many <Invented name> tablets. Taking too much <Invented name> increases the risk of bleeding.

If you forget to take <Invented name>

Do not take a double dose to make up for a missed dose. If you miss a dose, take your next dose at the usual time.

If you stop taking <Invented name>

Take <Invented name> on a regular basis and for as long as your doctor keeps prescribing it.

Do not stop taking <Invented name> without talking to your doctor first. If you stop taking this medicine, it may increase your risk of having another heart attack or stroke or dying from a disease related to your heart or your blood vessels.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist .

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Like other similar medicines to reduce the formation of blood clots, <Invented name> may cause bleeding which may potentially be life threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). In some cases the bleeding may not be obvious.

Tell your doctor immediately if you experience any of the following side effects:

Signs of bleeding

• bleeding into the brain or inside the skull (symptoms can include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness. A serious medical emergency. Seek medical attention immediately!) - long or excessive bleeding
• exceptional weakness, tiredness, paleness, dizziness, headache, unexplained swelling, breathlessness, chest pain or angina pectoris

Your doctor may decide to keep you under closer observation or change the treatment.

Signs of severe skin reactions

• spreading intense skin rash, blisters or mucosal lesions, e.g. in the mouth or eyes

  (Stevens-Johnson syndrome/toxic epidermal necrolysis).

• a drug reaction that causes rash, fever, inflammation of internal organs, blood abnormalities and systemic illness (DRESS syndrome).

  The frequency of these side effects is very rare (up to 1 in 10,000 people).

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 people) and uncommon (angioedema and allergic oedema; may affect up to 1 in 100 people).

Overall list of possible side effects

Common (may affect up to 1 in 10 people)

• reduction in red blood cells which can make the skin pale and cause weakness or breathlessness
• bleeding in the stomach or bowel, urogenital bleeding (including blood in the urine and heavy menstrual bleeding), nose bleed, bleeding in the gum
• bleeding into the eye (including bleeding from the whites of the eyes) - bleeding into tissue or a cavity of the body (haematoma, bruising) - coughing up blood
• bleeding from the skin or under the skin
• bleeding following an operation
• oozing of blood or fluid from surgical wound
• swelling in the limbs
• pain in the limbs
• impaired function of the kidneys (may be seen in tests performed by your doctor) - fever
• stomach ache, indigestion, feeling or being sick, constipation, diarrhoea - low blood pressure (symptoms may be feeling dizzy or fainting when standing up) - decreased general strength and energy (weakness, tiredness), headache, dizziness - rash, itchy skin
• blood tests may show an increase in some liver enzymes

Uncommon (may affect up to 1 in 100 people)

• bleeding into the brain or inside the skull (see above, signs of bleeding) - bleeding into a joint causing pain and swelling
• thrombocytopenia (low number of platelets, which are cells that help blood to clot) - allergic reactions, including allergic skin reactions
• impaired function of the liver (may be seen in tests performed by your doctor) - blood tests may show an increase in bilirubin, some pancreatic or liver enzymes or in the number of platelets
• fainting
• feeling unwell
• faster heartbeat
• dry mouth
• hives

Rare (may affect up to 1 in 1,000 people)

• bleeding into a muscle
• cholestasis (decreased bile flow), hepatitis incl. hepatocellular injury (inflamed liver incl. liver injury)
• yellowing of the skin and eye (jaundice)
• localised swelling
• collection of blood (haematoma) in the groin as a complication of the cardiac procedure where a catheter is inserted in your leg artery (pseudoaneurysm)

Not known (frequency cannot be estimated from the available data)

• kidney failure after a severe bleeding
• increased pressure within muscles of the legs or arms after a bleeding, which leads to pain, swelling, altered sensation, numbness or paralysis (compartment syndrome after a bleeding)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store <Invented name>

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 packaging and the blister after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What <Invented name> contains

• The active substance is rivaroxaban. Each film-coated tablet contains 2.5 mg rivaroxaban.
• The other ingredients (excipients) are mannitol, microcrystalline cellulose, macrogol, poloxamer, sodium laurilsulfate, sodium croscarmellose, colloidal anhydrous silica, sodium stearyl fumarate in the tablet core and hypromellose, macrogol, titanium dioxide (E171) and yellow iron oxid (E172) in the film coating. See section 2 "<Invented name> contains sodium".

What <Invented name> looks like and contents of the pack

Film-coated tablets (tablets) are pale brownish yellow to brownish yellow, round, slightly biconvex engraved with mark 2.5 on one side of the tablet. Dimensions: diameter approximately 6.5 mm.

<Invented name> is available in boxes containing:

• 10, 15, 30, 50, 60, 90 and 100 film-coated tablets, in non-perforated blister. - 10 x 1, 30 x 1, 50 x 1, 60 x 1, 90 x 1 and 100 x 1 film-coated tablets, in perforated unit dose blister.
• calendar pack: 14, 28, 42, 56, 98, 168 and 196 film-coated tablets, in non-perforated blister.

Patient Alert Card is included in each medicine pack.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

[To be completed nationally]

This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland)under the following names:

This leaflet was last revised in

[To be completed nationally]