RIVAROXABAN COMBIX 20 mg FILM-COATED TABLETS

2. What you need to know before taking Rivaroxaban Combix

Do not take Rivaroxaban Combix

• if you are allergic to rivaroxaban or any of the other ingredients of this medication (listed in section 6)
• if you have excessive bleeding
• if you have a disease or problem in an organ of the body that increases the risk of severe bleeding (e.g., stomach ulcer, injury or bleeding in the brain, or recent brain or eye surgery)
• if you are taking medications to prevent blood clotting (e.g., warfarin, dabigatran, apixaban, or heparin), except when switching to another anticoagulant treatment or while being administered heparin through a venous or arterial catheter to prevent it from becoming blocked
• if you have a liver disease that increases the risk of bleeding
• if you are pregnant or breastfeeding

Do not take this medication and inform your doctorif any of these circumstances apply to you.

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medication.

Be careful with Rivaroxaban Combix

• if you have an increased risk of bleeding, as may occur in the following situations:
• • moderate kidney failure, as kidney function may affect the amount of medication that works in your body
  • if you are taking other medications to prevent blood clotting (e.g., warfarin, dabigatran, apixaban, or heparin) when switching to another anticoagulant treatment or while receiving heparin through a venous or arterial catheter to prevent it from becoming blocked (see section "Other medications and Rivaroxaban Combix")
  • bleeding disorder
  • very high blood pressure that is not controlled by medical treatment
  • diseases of the stomach or intestine that may cause bleeding, such as inflammation of the stomach or intestine, inflammation of the esophagus (e.g., due to gastroesophageal reflux disease)
  • a problem in the blood vessels of the back of the eyes (retinopathy)
  • a lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or a previous lung hemorrhage
• if you have a heart valve prosthesis
• 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 it may be necessary to modify the treatment
• 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 situationsbefore taking this medication. Your doctor will decide if you should be treated with this medication and if you should be kept under closer observation.

If you need surgery:

• It is very important to take rivaroxaban before and after surgery, exactly at the times indicated by your doctor.
• If your operation requires the placement of a catheter or injection into the spinal column (e.g., for epidural or spinal anesthesia, or pain relief):
• • It is very important to take rivaroxaban before and after the injection or removal of the catheter, exactly at the times indicated by your doctor.
  • Inform your doctor immediately if you experience numbness or weakness in the legs or problems in the intestine or bladder after anesthesia, as urgent attention is necessary.

Children and adolescents

This medication is not recommended for children under 18 years of age.There is not enough information about its use in children and adolescents.

Other medications and Rivaroxaban Combix

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication, including those purchased without a prescription.

• If you are taking:
• • any medication 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 medication for bacterial infections (e.g., clarithromycin, erythromycin)
  • any antiviral medication for HIV/AIDS (e.g., ritonavir)
  • other medications to reduce blood clotting (e.g., enoxaparin, clopidogrel, or vitamin K antagonists, such as warfarin or acenocoumarol)
  • anti-inflammatory medications or pain relievers (e.g., naproxen or acetylsalicylic acid)
  • dronedarone, a medication for the treatment of irregular heartbeat
  • certain medications for the treatment of depression (selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs))

If any of the above circumstances apply to you, inform your doctorbefore taking this medication, as the effect of rivaroxaban may be increased. Your doctor will decide if you should be treated with this medication and if you should be kept under closer observation.

If your doctor considers that you have a higher risk of developing stomach or intestinal ulcers, they will recommend using a preventive treatment in addition.

If you are taking:

• any medication for the treatment of epilepsy (phenytoin, carbamazepine, phenobarbital)
• St. John's Wort (Hypericum perforatum), a medicinal plant for the treatment of depression
• rifampicin, an antibiotic

If any of the above circumstances apply to you, inform your doctorbefore taking this medication, as the effect of rivaroxaban may be decreased. Your doctor will decide if you should be treated with this medication and if you should be kept under closer observation.

Pregnancy and breastfeeding

DO NOT take rivaroxaban if you are pregnant or breastfeeding. If there is any possibility that you may become pregnant, use a reliable contraceptive while taking rivaroxaban. If you become pregnant while taking this medication, inform your doctor immediately, who will decide how you should be treated.

Driving and using machines

This medication may cause dizziness (frequent side effect) or fainting (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 Combix contains lactose and sodium

This medication contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

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

3. How to take Rivaroxaban Combix

Follow the administration instructions of this medication exactly as indicated by your doctor. If you have any doubts, consult your doctor or pharmacist again.

What dose to take

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

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

If you have kidney problems, the dose may be reduced to one 15 mg rivaroxaban 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 placement), there is limited evidence to reduce the dose to one 15 mg rivaroxaban tablet once a day (or to one 10 mg rivaroxaban tablet once a day if your kidneys do not function properly) in addition to an antiplatelet medication such as clopidogrel.

• To treat blood clots in the veins of the legs and in the blood vessels of the lungs, and to prevent these blood clots from occurring again:

The recommended dose is one 15 mg rivaroxaban tablet twice a day for the first 3 weeks. For treatment after 3 weeks, the recommended dose is one 20 mg rivaroxaban tablet once a day.

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

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

Swallow the tablet, preferably with water.

Take Rivaroxaban Combix with food.

If you have difficulty swallowing the whole tablet, consult your doctor about other ways to take rivaroxaban.

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 tablet through a gastric tube

When to take Rivaroxaban Combix

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 continue taking the treatment.

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

If you need to undergo a procedure to normalize your heartbeat, called cardioversion, take rivaroxaban at the times indicated by your doctor.

If you take more Rivaroxaban Combix than you should

Call your doctor immediately if you have taken too many rivaroxaban tablets. Taking too much rivaroxaban 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 medication and the amount taken.

If you forget to take Rivaroxaban Combix

• If you are taking one 20 mg or one 15 mg tablet once a day, and you forget to take a dose, take it as soon as you remember. Do not take more than one tablet in a single day to make up for a forgotten dose. Take the next tablet the next day and, after that, continue taking one tablet every day.

• If you are taking one 15 mg tablet twice a day and you forget to take a dose, take it as soon as you remember. Do not take more than two 15 mg tablets in a single day. If you forget to take a dose, you can take two 15 mg tablets at the same time, for a total of two tablets (30 mg) in a day. The next day, you should continue taking one 15 mg tablet twice a day.

If you interrupt treatment with Rivaroxaban Combix

Do not interrupt treatment with rivaroxaban without first talking to your doctor, as Rivaroxaban prevents the development of a serious condition.

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

4. Possible Adverse Effects

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

Like other similar medicines to reduce blood clot formation, rivaroxaban can cause bleeding, which can put the patient's life at risk. 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 experience any of the following symptoms:

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

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

• Signs of severe skin reactions
• • Severe 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

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:

Frequent(may affect up to 1 in 10 people):

• Decrease in red blood cells, which 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 from the 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.
• Pus or fluid discharge 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 dizziness or fainting 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.
• 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 (decrease in bile flow), hepatitis, including traumatic hepatocellular injury (inflammation or 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).

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

• Increased pressure in the muscles of the legs or arms after bleeding, causing pain, swelling, altered sensation, numbness, or paralysis (compartment syndrome due to bleeding).
• Kidney failure after severe bleeding, bleeding in the kidney, sometimes with blood in the urine, which causes the kidneys to malfunction (anticoagulant-related nephropathy).

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 prospectus. You can also report it directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Rivaroxaban Combix

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging, 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 you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Rivaroxaban Combix

• The active ingredient is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.
• The other components are:

Core of the tablet:microcrystalline cellulose, lactose monohydrate, sodium croscarmellose, hypromellose, sodium lauryl sulfate, magnesium stearate.

Coating of Rivaxoraban Combix 15 mg film-coated tablets:

composed of hypromellose, macrogol, red iron oxide (E172), talc, titanium dioxide (E 171).

Coating of Rivaxoraban Combix 20 mg film-coated tablets:

composed of hypromellose, macrogol, red iron oxide (E172), talc, titanium dioxide (E 171).

Appearance of the product and package contents

Rivaroxabán Combix 15 mg:

Red to brown, round, biconvex, and smooth film-coated tablets on both sides. The diameter of the tablet is approximately 5.65 mm. The tablets are available in blisters in packs of 28 or 42 tablets.

Rivaroxabán Combix 15 mg:

Rivaroxabán Combix 20 mg: Red to brown, round, biconvex, scored on one side and smooth on the other side. The score line is only for breaking and facilitating swallowing, but not for dividing into equal doses. The diameter of the tablet is approximately 6.40 mm. The tablets are available in blisters in packs of 28 tablets.

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

O

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

O

Netpharmalab Consulting Services

Carretera de Fuencarral 22

28108 Alcobendas, Madrid

Spain

O

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

O

Flavine Pharma France

3 Voie d’Allemagne

13127 Vitrolles

France

Date of the last revision of this prospectus: September 2023

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