RIVAROXABAN COMBIX 10 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Rivaroxaban Combix 10 mg Film-Coated Tablets EFG

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are side effects not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Rivaroxaban Combix and what is it used for
2. What you need to know before taking Rivaroxaban Combix
3. How to take Rivaroxaban Combix
4. Possible side effects
5. Storage of Rivaroxaban Combix
6. Package contents and additional information

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

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

• preventing the formation of blood clots in the veins after hip or knee replacement surgery. Your doctor has prescribed this medication because after surgery you have a higher risk of forming blood clots.
• treating 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 occurring again in the blood vessels of the legs and/or lungs.

This medication belongs to a group of medications called antithrombotic agents. It works by blocking a clotting factor (factor Xa) and thus reducing the tendency of blood to form clots.

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 components of this medication (listed in section 6)
• if you bleed excessively
• if you have a disease or problems 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 clot formation (e.g., warfarin, dabigatran, apixaban, or heparin), except when switching to anticoagulant treatment or while being administered heparin through a venous or arterial catheter, so that it does not become obstructed
• 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 or severe 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 clot formation (e.g., warfarin, dabigatran, apixaban, or heparin), when switching to another anticoagulant treatment or while receiving heparin through a venous or arterial catheter, so that it does not become obstructed (see section "Other medications and Rivaroxaban Combix")
  • bleeding disorder
  • very high blood pressure, not controlled by medical treatment
  • stomach or intestinal diseases that may cause bleeding, such as inflammation of the stomach or intestine, inflammation of the esophagus (throat), e.g., due to gastroesophageal reflux disease (a disease in which stomach acid rises up into the esophagus)
  • 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 previous lung bleeding
• 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 clot formation), inform your doctor to decide if it may be necessary to modify treatment
• if your doctor determines that your blood pressure is unstable or 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 exactly at the times indicated by your doctor.
  • Inform your doctor immediately if you experience numbness or weakness in your legs or problems in your intestines or bladder at the end of 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 obtained without a prescription.

• If you are taking:
• • any medication for a fungal infection (e.g., fluconazole, itraconazole, voriconazole, posaconazole), unless only applied to the skin
  • tablets with ketoconazole (used to treat Cushing's syndrome, in which the body produces excess 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 and 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 increase. 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 for ulcers in addition to this medication.

If you take:

• 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 reduced. 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. In case of doubt, consult your doctor or pharmacist again.

What dose to take

• To prevent the formation of blood clots in the veins after hip or knee replacement surgery.

The recommended dose is one 10 mg rivaroxaban tablet once a day.

• 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.

After at least 6 months of treatment for blood clots, the recommended dose is one 10 mg tablet once a day or one 20 mg tablet once a day. Your doctor has prescribed rivaroxaban 10 mg once a day.

You should take Rivaroxaban 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. The tablet can be crushed and mixed with water or apple puree, 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 one tablet every day, until your doctor indicates otherwise.

Try to take one tablet at the same time every day, to help you remember. The doctor will decide how long you should continue treatment.

To prevent the formation of blood clots in the veins after hip or knee replacement surgery:

Take the first tablet 6 to 10 hours after surgery.

If you have undergone major hip surgery, you will usually take tablets for 5 weeks. If you have undergone major knee surgery, you will usually take tablets for 2 weeks.

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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Rivaroxaban Combix

If you forget to take a dose, take it as soon as you remember. Take the next tablet the next day and, after that, take one tablet every day, as usual.

Do not take a double dose to make up for forgotten doses

If you stop taking Rivaroxaban Combix

Do not stop 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 side effects

Like all medications, rivaroxaban can cause side effects, although not everyone will experience them.

Like other similar medications to reduce blood clot formation, rivaroxaban can cause bleeding, which can be life-threatening. Excessive bleeding can cause a sudden drop in blood pressure (shock). In some cases, the bleeding may not be apparent.

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

• severe skin rash that spreads, 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 this side effect 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 side effects:

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

• decrease in red blood cells that can cause paleness and weakness or difficulty breathing
• stomach or intestinal bleeding, urogenital bleeding (including blood in the urine and heavy menstrual bleeding), nasal bleeding, gum bleeding
• 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 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 patients):

• 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 clot)
• 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 patients):

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

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

• kidney failure after severe bleeding, kidney bleeding, sometimes with blood in the urine, which causes the kidneys to fail to function properly (anticoagulant-related nephropathy)
• 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)

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are side effects not listed in this package leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Rivaroxaban Combix

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

Do not use this medication after the expiration date that appears on the packaging, after "EXP". The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. Ask your pharmacist how to dispose of the packaging and medications 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 10 mg of rivaroxaban.
• The other components are:

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

Coating:composed of hypromellose, macrogol, talc, red iron oxide (E172), titanium dioxide (E171).

Appearance of the Product and Package Contents

Rivaroxaban Combix 10 mg is a film-coated tablet, round, biconvex, pink or light pink in color, and smooth on both sides. The diameter of the tablet is approximately 6.40 mm. The tablets are presented in blisters available in packages of 10 or 30 tablets.

Marketing Authorization Holder

Combix Laboratories, S.L.U.

C/ Badajoz 2, Building 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

Or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Or

Netpharmalab Consulting Services

Carretera de Fuencarral 22

28108 Alcobendas, Madrid

Spain

Or

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

Or

Flavine Pharma France

3 Voie d’Allemagne

13127 Vitrolles

France

Date of the Last Revision of this Leaflet: September 2023

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