RIVAROXABAN ZENTIVA 20 mg FILM-COATED TABLETS

1. What is Rivaroxaban Zentiva and what is it used for

Rivaroxaban Zentiva contains the active substance rivaroxaban and is used in adults to:

• prevent the formation of blood clots in the veins after hip or knee replacement surgery. Your doctor has prescribed this medicine because after an operation you are at a higher risk of forming blood clots.
• 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 these blood clots from happening again in the blood vessels of the legs and/or lungs.

Rivaroxaban Zentiva is used in children and adolescents under 18 years of age and with a body weight of 30 kg or more to:

• treat and prevent blood clots in the veins or in the blood vessels of the lungs, after initial treatment for at least 5 days with injectable medicines used to treat blood clots.

Rivaroxaban Zentiva belongs to a group of medicines called antithrombotic agents. It works by blocking a factor in the blood (factor Xa) involved in blood clotting, thus reducing the tendency of the blood to form clots.

2. What you need to know before you take Rivaroxaban Zentiva

Do not take Rivaroxaban Zentiva

• if you are allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6);
• if you have bleeding problems;
• if you have a disease or condition that increases the risk of serious bleeding (e.g. stomach ulcer, recent injury or bleeding in the brain, or recent brain or eye surgery);
• if you are taking other medicines to prevent blood clots (e.g. warfarin, dabigatran, apixaban, or heparin), except when switching to this medicine or while receiving heparin through a venous or arterial catheter to keep it from getting blocked;
• if you have a liver disease that increases the risk of bleeding;
• if you are pregnant or breastfeeding.

Do not take Rivaroxaban Zentiva and inform your doctorif any of these apply to you.

Warnings and precautions

Consult your doctor or pharmacist before taking Rivaroxaban Zentiva.

Be particularly careful with Rivaroxaban Zentiva

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

• moderate or severe kidney problems, as kidney function may affect the amount of medicine that works in your body;
• if you are taking other medicines to prevent blood clots (e.g. warfarin, dabigatran, apixaban, or heparin) when switching to this medicine or while receiving heparin through a venous or arterial catheter to keep it from getting blocked (see section "Other medicines and Rivaroxaban Zentiva");
• bleeding disorders;
• uncontrolled high blood pressure;
• stomach or intestinal diseases that may cause bleeding, such as inflammation of the stomach or intestines, inflammation of the esophagus (e.g. due to gastroesophageal reflux disease), or tumors in the stomach, intestines, genital tract, or urinary tract;
• problems with blood vessels in the back of the eyes (retinopathy);
• a lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding;

• if you have a heart valve replacement;
• if you know you have a disease called antiphospholipid syndrome (an immune system disorder that increases the risk of blood clots), inform your doctor to decide if treatment needs to be modified;
• if your doctor determines that your blood pressure is unstable or if you are scheduled to receive another treatment or undergo surgery to remove a blood clot from your lungs.

Inform your doctor if you have any of these conditionsbefore taking Rivaroxaban Zentiva. 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 surgery

• it is very important to take Rivaroxaban Zentiva before and after surgery, exactly at the times your doctor tells you.
• if your operation requires the placement of a catheter or injection into the spine (e.g. for epidural or spinal anesthesia, or pain relief):

• it is very important to take Rivaroxaban Zentiva exactly at the times your doctor tells you
• tell your doctor immediately if you experience numbness or weakness in your legs or problems with your intestines or bladder after anesthesia, as urgent attention is needed.

Children and adolescents

Rivaroxaban Zentiva 20 mg tablets are not recommended in children with a body weight below 30 kg. There is not enough information on the use of Rivaroxaban Zentiva in children and adolescents for adult indications.

.

Other medicines and Rivaroxaban Zentiva

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

• If you are taking
• • any medicine for a fungal infection (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless it is only applied to the skin;
  • ketoconazole tablets (used to treat Cushing's syndrome, in which the body produces too much cortisol);
  • any medicine for bacterial infections (e.g. clarithromycin, erythromycin);
  • any antiviral medicine for HIV/AIDS (e.g. ritonavir);
  • other medicines to prevent blood clots (e.g. enoxaparin, clopidogrel, or vitamin K antagonists, such as warfarin or acenocoumarol);
  • anti-inflammatory medicines or pain relievers (e.g. naproxen or acetylsalicylic acid);
  • dronedarone, a medicine for irregular heartbeat;
  • certain medicines for depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs)).

If any of these apply to you, inform your doctorbefore taking Rivaroxaban Zentiva, as the effect of Rivaroxaban Zentiva 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 considers that you are at a higher risk of developing stomach or intestinal ulcers, they will recommend that you also take a medicine to prevent ulcers.

• If you are taking
• • any medicine for epilepsy (phenytoin, carbamazepine, phenobarbital);
  • St. John's Wort (Hypericum perforatum), a herbal medicine for depression;
  • rifampicin, an antibiotic.

If any of these apply to you, inform your doctorbefore taking Rivaroxaban Zentiva, as the effect of Rivaroxaban Zentiva may be reduced. Your doctor will decide if you should be treated with Rivaroxaban Zentiva and if you should be kept under closer observation.

Pregnancy and breastfeeding

Do not take Rivaroxaban Zentiva if you are pregnant or breastfeeding. If there is a possibility that you may become pregnant, use a reliable contraceptive while taking Rivaroxaban Zentiva. If you become pregnant while taking this medicine, inform your doctor immediately, who will decide how you should be treated.

Driving and using machines

Rivaroxaban Zentiva may cause dizziness (a common side effect) or fainting (an uncommon side effect) (see section 4, "Possible side effects"). You should not drive, ride a bicycle, or use tools or machines if you are affected by these symptoms.

Rivaroxaban Zentiva contains lactose and sodium

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take Rivaroxaban Zentiva

Follow exactly the instructions of your doctor. If you are unsure, consult your doctor or pharmacist again.

You should take Rivaroxaban Zentiva with food. Swallow the tablets, preferably with water.

If you have difficulty swallowing the tablet whole, consult your doctor about other ways to take Rivaroxaban Zentiva. The tablet can be crushed and mixed with water or apple sauce, immediately before taking it. Then take food.

If necessary, your doctor may also administer the crushed Rivaroxaban Zentiva tablet through a gastric tube.

What dose to take

• Adults
• • To prevent the formation of blood clots in the brain (stroke) or in other blood vessels

The recommended dose is one Rivaroxaban Zentiva 20 mg tablet once a day.

If you have kidney problems, the dose may be reduced to one Rivaroxaban Zentiva 15 mg tablet once a day.

If you need to undergo a procedure to treat blocked blood vessels in your heart (called percutaneous coronary intervention - PCI with stent insertion), there is limited evidence to reduce the dose to one Rivaroxaban Zentiva 15 mg tablet once a day (or to one Rivaroxaban Zentiva 10 mg tablet once a day if your kidneys do not work properly) in addition to an antiplatelet medicine like clopidogrel.

• To treat blood clots in the veins of the legs and in the blood vessels of the lungs, and to prevent blood clots from happening again.

The recommended dose is one Rivaroxaban Zentiva 15 mg tablet twice a day for the first 3 weeks.

For treatment after 3 weeks, the recommended dose is one Rivaroxaban Zentiva 20 mg tablet once a day.

After at least 6 months of treatment for blood clots, your doctor may decide to continue treatment with one Rivaroxaban Zentiva 10 mg tablet once a day or one Rivaroxaban Zentiva 20 mg tablet once a day.

If you have kidney problems and are taking one Rivaroxaban Zentiva 20 mg tablet once a day, your doctor may decide to reduce the treatment dose to one Rivaroxaban Zentiva 15 mg tablet once a day after 3 weeks if the risk of bleeding is higher than the risk of having another blood clot.

• Children and adolescents

The dose of Rivaroxaban Zentiva depends on body weight and will be calculated by your doctor.

• The recommended dose for children and adolescents with a body weight of 30 kg to less than 50 kgis one Rivaroxaban Zentiva 15 mgtablet once a day.
• The recommended dose for children and adolescents with a body weight of 50 kg or moreis one Rivaroxaban Zentiva 20 mg tablet once a day.

Take each dose of Rivaroxaban Zentiva with a drink (e.g. water or juice) during a meal. Take the tablets every day at about the same time. Consider setting an alarm to remind you.

For parents or caregivers: observe the child to ensure they take the entire dose.

Since the dose of Rivaroxaban Zentiva is based on body weight, it is important to attend scheduled visits with your doctor, as the dose may need to be adjusted as the weight changes.

Do not split the tablet to try to get a fraction of the tablet dose. If a smaller dose is required, please use the alternative presentation of rivaroxaban granules for oral suspension.

In children and adolescents who cannot swallow whole tablets, please use rivaroxaban granules for oral suspension.

If the oral suspension is not available, you can crush the Rivaroxaban Zentiva tablet and mix it with water or apple sauce immediately before taking it. Take some food after taking this mixture. If necessary, your doctor may also administer the crushed Rivaroxaban Zentiva tablet through a gastric tube.

If you spit up the dose or vomit

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

Call your doctor if you spit up the dose or vomit repeatedly after taking Rivaroxaban Zentiva

When to take Rivaroxaban Zentiva

Take the tablet every day, until your doctor tells you to stop.

Try to take a tablet at the same time every day, to help you remember. Your doctor will decide how long you should keep taking the treatment.

To prevent the formation of blood clots in the brain (stroke) or in other blood vessels:

If it is necessary to normalize your heartbeat through a procedure called cardioversion, take Rivaroxaban Zentiva at the times your doctor has indicated.

If you take more Rivaroxaban Zentiva than you should

Call your doctor immediately if you have taken too many Rivaroxaban Zentiva tablets. Taking too much Rivaroxaban Zentiva increases the risk of bleeding.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Rivaroxaban Zentiva

• Adults, children, and adolescents:

If you are taking one 20 mg tablet oncea day, 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 a missed dose. Take the next tablet the next day and then continue taking one tablet every day.

• Adults:

If you are taking one 15 mg tablet twicea day, 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 can take two 15 mg tablets at the same time, for a total of two tablets (30 mg) in one day. The next day, you should continue taking one 15 mg tablet twice a day.

If you stop taking Rivaroxaban Zentiva

Do not stop taking Rivaroxaban Zentiva without talking to your doctor first, because Rivaroxaban Zentiva prevents the development of a serious condition.

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

4. Possible Adverse Effects

Like all medicines, Rivaroxaban Zentiva can cause adverse effects, although not all people suffer from them.

Like other similar medicines to reduce blood clot formation, Rivaroxaban Zentiva can cause bleeding, which can endanger the patient's life. Excessive bleeding can cause a sudden drop in blood pressure (shock). In some cases, the bleeding may not be evident.

Tell your doctor immediately if you suffer from any of the following adverse effects:

• Signs of bleeding
• • bleeding in the brain or inside the skull (symptoms may include headache, weakness on one side of the body, vomiting, seizures, decreased level of consciousness, and stiffness in the neck. This is a serious medical emergency. Go to the doctor immediately!).

• prolonged and excessive bleeding.
• exceptional weakness, fatigue, paleness, dizziness, headache, unexplained swelling, difficulty breathing, chest pain or angina.

Your doctor will decide to keep you under closer observation or modify your treatment.

• Signs of severe skin reactions

• intense skin rashes that spread, blisters, or lesions on the mucous membranes, e.g., in the mouth or eyes (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• drug reaction that causes rash, fever, inflammation of internal organs, blood abnormalities, and systemic disease (DRESS syndrome).

The frequency of these adverse 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 difficulty breathing; 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 edema; may affect up to 1 in 100 people).

General list of possible adverse effects found in adults, children, and adolescents

Frequent(may affect up to 1 in 10 people)

• decrease in red blood cells that can cause paleness and weakness or difficulty breathing
• bleeding in the stomach or intestine, urogenital hemorrhage (including blood in the urine and heavy menstrual bleeding), nasal bleeding, bleeding gums
• bleeding in the eye (including bleeding in the white part of the eye)
• bleeding into a tissue or cavity of the body (hematoma, bruising)
• coughing up blood
• bleeding from the skin or under the skin
• bleeding after surgery
• oozing of blood or fluid from a surgical wound
• swelling of the limbs
• pain in the limbs
• alteration of kidney function (may be seen in tests performed by the doctor)
• fever
• stomach pain, indigestion, dizziness, or feeling of dizziness, constipation, diarrhea
• low blood pressure (symptoms may include feeling dizzy or faint when standing up)
• general decrease in strength and energy (weakness, fatigue), headache, dizziness
• rash, itching of the skin
• blood tests may show an increase in some liver enzymes

Uncommon(may affect up to 1 in 100 people)

• bleeding in the brain or inside the skull (see above, signs of bleeding)
• bleeding in a joint, causing pain and swelling
• thrombocytopenia (low platelet count, cells that help blood clotting)
• allergic reaction, including skin allergic reaction
• alteration of liver function (may be seen in tests performed by the doctor)
• blood tests may show an increase in bilirubin, some pancreatic or liver enzymes, or platelet count
• fainting
• feeling of discomfort
• increased heart rate
• dry mouth
• hives

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

• bleeding in a muscle
• cholestasis (decreased bile flow), hepatitis, including hepatocellular injury (liver inflammation, including liver damage)
• yellowing of the skin and eyes (jaundice)
• localized swelling
• blood accumulation (hematoma) in the groin as a complication after cardiac surgery in which a catheter is inserted into the leg artery (pseudoaneurysm)

Very Rare(may affect up to 1 in 10,000 people)

• accumulation of eosinophils, a type of granulocytic white blood cells that cause inflammation in the lung (eosinophilic pneumonia)

Frequency Not Known(cannot be estimated from the available data)

• renal failure after severe bleeding
• increased pressure in the muscles of the legs or arms after bleeding, causing pain, swelling, altered sensation, numbness, or paralysis (hemorrhagic compartment syndrome)

Adverse Effects in Children and Adolescents

In general, the adverse effects observed in children and adolescents treated with rivaroxaban were similar to those observed in adults and their severity was mainly mild to moderate.

Adverse effects that were more frequently observed in children and adolescents:

Very Frequent(may affect more than 1 in 10 people)

• headache
• fever
• nasal bleeding
• vomiting

Frequent(may affect up to 1 in 10 people)

• accelerated heart rate
• blood tests may show an increase in bilirubin (bile pigment)
• thrombocytopenia (low platelet count, cells that help blood clotting)
• heavy menstrual bleeding

Uncommon(may affect up to 1 in 100 people)

• blood tests may show an increase in a subcategory of bilirubin (direct bilirubin, bile pigment)

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Rivaroxaban Zentiva

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging and on the blister, after "CAD". The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines that you no longer need in the SIGRE collection point at the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Rivaroxaban Zentiva

• The active ingredient is rivaroxaban. Each tablet contains 20 mg of rivaroxaban.
• The other components are:

• Core of the tablet: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose, sodium lauryl sulfate, and magnesium stearate.
• Coating of the tablet (OPADRY BROWN 03F565080): hypromellose, titanium dioxide (E-171), macrogol 3350, red iron oxide (E-172).

Appearance of the Product and Package Contents

Rivaroxaban Zentiva 20 mg film-coated tablets are brown-red in color, round, biconvex, film-coated (approximately 10.5 mm in diameter), with "20" embossed on one side and smooth on the other side.

Rivaroxaban Zentiva 20 mg is available in packages of 10, 14, 28, 30, 50, 98, and 100 film-coated tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder

Zentiva k.s.

U Kabelovny 130,

Dolní Mecholupy

102 37 Prague 10

Czech Republic

Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola

PLA3000 Malta

or

S.C Zentiva S.A.

B-dul Theodor Pallady nr. 50,

sector 3,

Bucharest, cod 032266

Romania

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Czech Republic, Austria, Denmark, Spain, Hungary, Iceland, Norway, Netherlands, Sweden, and Germany: Rivaroxaban Zentiva

Croatia: Rivaroksaban Zentiva

France: RIVAROXABAN ZENTIVA

Italy: Rivaroxaban Zentiva Italia

Portugal: Rivaroxabano Zentiva

Date of the Last Revision of this Leaflet:December 2023

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es