Rivahib

Package leaflet: Information for the patient

Varodoax, 2.5 mg, coated tablets
Rivaroxabanum
This medicinal product will be subject to additional monitoring. This will allow rapid

identification of new safety information. Patients can help by reporting any side effects that occur after starting treatment.
For information on how to report side effects – see section 4.
Please read carefully this leaflet 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Varodoax is and what it is used for

You have been prescribed Varodoax because:

• You have been diagnosed with acute coronary syndrome (a condition including heart attack and unstable angina, i.e. acute chest pain) and elevated levels of cardiac biomarkers have been confirmed. Varodoax reduces in adults the risk of further heart attack or reduces the risk of death due to heart or blood vessel disease. Varodoax will not be given to you as a single treatment. Your doctor will also prescribe you:
  • acetylsalicylic acid, or
  • acetylsalicylic acid and clopidogrel or ticlopidine.

or

• You are at high risk of developing blood clots due to coronary artery disease or peripheral arterial disease causing symptoms. Varodoax reduces in adults the risk of blood clots (atherosclerotic thrombotic events). Varodoax will not be given to you as a single treatment. Your doctor will also prescribe you acetylsalicylic acid. In certain cases, if you are receiving Varodoax following a procedure to open a narrowed or blocked artery in the lower limb to restore blood flow, your doctor may also prescribe clopidogrel to be taken for a short period in addition to acetylsalicylic acid.

Varodoax contains the active substance rivaroxaban and belongs to a group of medicines called anticoagulants. It works by blocking a blood clotting factor (factor Xa), thereby reducing the tendency for blood clots to form.

2. Important information before taking Varodoax

When not to take Varodoax

• if the patient is allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6),
• if the patient has active bleeding,
• if the patient has a disease or condition of an organ that leads to an increased risk of serious bleeding (e.g., peptic ulcer, trauma or intracranial bleeding, recent brain or eye surgery),
• if the patient is taking other anticoagulant medicines (e.g., warfarin, dabigatran, apixaban, or heparin), except when switching anticoagulant therapy or if heparin is administered to maintain catheter patency in a vein or artery,
• if the patient has been diagnosed with acute coronary syndrome and previously experienced bleeding or blood clots in the brain (stroke),
• if the patient has coronary artery disease or peripheral arterial disease and previously had intracranial bleeding (hemorrhagic stroke), blockage of small arteries supplying blood to deep brain structures (lacunar stroke), or ischemic non-lacunar stroke within the past month,
• if the patient has a liver disease that increases the risk of bleeding,
• if the patient is pregnant or breastfeeding. Do not use Varodoax and inform your doctor if you suspect any of the above conditions apply.

Warnings and precautions
Before starting Varodoax, discuss this with your doctor or pharmacist.
Varodoax should not be used in combination with certain other antiplatelet medicines such as prasugrel or ticagrelor, other than acetylsalicylic acid, clopidogrel, or ticlopidine.

When to exercise special caution when taking Varodoax

• if the patient has an increased risk of bleeding, such as in the following conditions:
• severe kidney disease, as kidney function may affect the amount of medicine acting in the patient's body,
• taking other medicines that prevent blood clots (e.g., warfarin, dabigatran, apixaban, or heparin) when switching anticoagulant therapy or when heparin is administered to maintain catheter patency in a vein or artery (see section "Varodoax with other medicines"),
• coagulation disorders,
• very high blood pressure that does not decrease despite treatment,
• stomach or intestinal diseases that may cause bleeding, e.g., gastrointestinal inflammation or esophagitis (e.g., due to gastroesophageal reflux disease—backflow of stomach acid into the esophagus) or tumors located in the stomach, intestines, genital or urinary tract,
• posterior segment blood vessel disease of the eye (retinopathy),
• lung disease with bronchiectasis (dilated bronchi filled with pus) or previous pulmonary bleeding,
• if the patient is over 75 years old,
• if the patient weighs less than 60 kg,
• coronary artery disease with severe symptomatic heart failure,
• in patients with heart valve prostheses,
• if the patient has a disorder called antiphospholipid syndrome (an autoimmune disorder increasing the risk of blood clots), the patient should inform the doctor, who will decide whether treatment adjustment is needed.

If the patient suspects any of the above conditions apply, inform the doctor before taking Varodoax. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.

If the patient requires surgery:

• strictly follow the doctor's instructions regarding the timing of Varodoax administration before or after surgery,
• if catheterization or spinal puncture (e.g., for epidural or spinal anaesthesia or pain relief) is planned during surgery:
  • it is very important to take Varodoax before and after the puncture or catheter removal exactly as directed by the doctor,
  • due to the need for special caution, immediately inform the doctor if numbness or weakness in the legs, or disturbances in bowel or bladder function occur after the anaesthesia ends.

Children and adolescents
Varodoax 2.5 mg tablets are not recommended for patients under 18 years of age. There is insufficient data on the use of this medicine in children and adolescents.

Varodoax with other medicines
Inform your doctor or pharmacist about all medicines currently taken, recently taken, or planned for use, including those obtained without a prescription.

• If the patient is taking:
  • certain antifungal medicines (e.g., fluconazole, itraconazole, voriconazole, posaconazole), unless used only topically on the skin,
  • ketoconazole tablets (used in the treatment of Cushing's syndrome, in which the body produces too much cortisol),
  • certain antibiotics (e.g., clarithromycin, erythromycin),
  • certain antiviral medicines used in HIV infection or AIDS treatment (e.g., ritonavir),
  • other medicines used to reduce blood clotting (e.g., enoxaparin, clopidogrel, or vitamin K antagonists such as warfarin or acenocoumarol, prasugrel, and ticagrelor (see section "Warnings and precautions")),
  • anti-inflammatory and pain medicines (e.g., naproxen or acetylsalicylic acid),
  • dronedarone, a medicine used to treat heart rhythm disorders,
  • certain antidepressants (selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs)).

If the patient suspects any of the above apply, inform the doctor before taking Varodoax, as the effect of Varodoax may be enhanced. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the doctor considers the patient to be at increased risk of developing stomach or intestinal ulcers, preventive treatment may be prescribed.

• If the patient is taking:
  • certain antiepileptic medicines (phenytoin, carbamazepine, phenobarbital),
  • St. John's wort (Hypericum perforatum), a herbal remedy used for depression,
  • rifampicin, an antibiotic.
    If the patient suspects any of the above apply, inform the doctor before taking Varodoax, as the effect of Varodoax may be reduced. The doctor will decide whether to use Varodoax and whether the patient requires particularly close monitoring.

Pregnancy and breastfeeding
Do not use Varodoax if the patient is pregnant or breastfeeding. If there is a risk that the patient may become pregnant, an effective method of contraception should be used during treatment with Varodoax. If the patient becomes pregnant while taking this medicine, she must inform her doctor immediately, who will decide on further management.

Driving and operating machinery
Varodoax may cause dizziness (common side effect) and fainting (uncommon side effect) (see section 4, "Possible side effects"). Patients experiencing these side effects should not drive, ride a bicycle, or operate tools or machinery.

Varodoax contains lactose and sodium.
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.
The medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning it is considered "sodium-free".

3. How to take Varodoax

This medicine should always be taken exactly as prescribed by the doctor. If in doubt,
contact your doctor or pharmacist.

How many tablets to take
The recommended dose is one 2.5 mg tablet twice daily. Varodoax should be taken at approximately the same time each day (for example, one tablet in the morning and one in the evening). This medicine can be taken with or without food.

If a patient has difficulty swallowing the whole tablet, they should speak to their doctor about alternative ways of taking Varodoax. The tablet may be crushed and mixed with water or apple puree immediately before administration.

If necessary, the doctor may administer crushed Varodoax tablets via a gastric tube.

Varodoax will not be given to the patient as the only medication.

Your doctor will prescribe acetylsalicylic acid for the patient to take.

If the patient is receiving Varodoax after an acute coronary syndrome, the doctor may also prescribe clopidogrel or ticlopidine.

If the patient is receiving Varodoax following a procedure to open a narrowed or blocked artery in the lower limb to restore blood flow, the doctor may also prescribe clopidogrel to be taken for a short time in addition to acetylsalicylic acid.

The doctor will inform the patient of the dose of these medicines to take (usually 75–100 mg of acetylsalicylic acid per day, or a daily dose of 75–100 mg acetylsalicylic acid plus a daily dose of 75 mg clopidogrel, or the standard daily dose of ticlopidine).

When to take Varodoax

Treatment with Varodoax after an acute coronary syndrome should be initiated as soon as possible after stabilization of the acute coronary syndrome, no earlier than 24 hours after hospital admission and at the time when parenteral (by injection) anticoagulant treatment would normally be discontinued.

The doctor will inform the patient when to start treatment with Varodoax if coronary artery disease or peripheral arterial disease has been diagnosed.

The doctor will decide how long treatment should continue.

Taking more than the recommended dose of Varodoax

If the patient has taken more than the recommended dose of Varodoax, they should contact their doctor immediately. Taking too high a dose of Varodoax increases the risk of bleeding.

Missed dose of Varodoax

Do not take a double dose to make up for a missed dose. If the patient misses a dose, they should take the next dose at the scheduled time.

Stopping Varodoax

Varodoax should be taken regularly and for the duration recommended by the doctor.

Do not stop taking Varodoax without first consulting your doctor. If treatment with this medicine is stopped, the risk of a further heart attack, stroke, or death due to heart or blood vessel disease may increase.

If there are any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicinal product may cause adverse reactions, although not in every individual.

As with other medicines of similar action that reduce blood clot formation, Varodoax may cause bleeding, which could potentially be life-threatening. Excessive bleeding may lead to sudden drop in blood pressure (shock). Signs of bleeding may not always be obvious or visible.

You should immediately inform your doctor if any of the following adverse reactions occur:

• Signs of bleeding:
  • bleeding into the brain or inside the skull (symptoms may include headache, one-sided paralysis, vomiting, seizures, decreased level of consciousness and neck stiffness. This is a serious, acute medical emergency. Immediate medical assistance must be called!)
  • prolonged or excessive bleeding,
  • unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina. Your doctor may decide that close monitoring of the patient or a change in treatment is necessary.
• Signs of severe skin reactions:
  • widespread, acute skin rash, blistering or mucosal lesions, e.g. on the tongue or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), characterized by rash, fever, internal organ inflammation, hematological disorders and systemic involvement. The frequency of these adverse reactions is very rare (up to 1 in 10,000 people).
• Signs of severe allergic reactions:
  • swelling of the face, lips, oral cavity, tongue or throat; urticaria and breathing difficulties; sudden drop in blood pressure. The frequency of severe allergic reactions is very rare (anaphylactic reactions, including anaphylactic shock, may occur in up to 1 in 10,000 people) and uncommon (angioedema and allergic edema may occur in 1 in 100 people).

General list of possible adverse reactions:
Common (may occur in up to 1 in 10 people)

• reduction in red blood cell count, which may cause paleness of the skin and lead to weakness or shortness of breath,
• gastrointestinal or intestinal bleeding, bleeding from the urinary or genital tract (including blood in urine and heavy menstrual bleeding), nosebleeds, gum bleeding,
• ocular bleeding (including bleeding from the white part of the eye),
• bleeding into tissues or body cavities (hematoma, bruising),
• presence of blood in sputum (hemoptysis) during coughing,
• skin bleeding or subcutaneous bleeding,
• postoperative bleeding,
• oozing of blood or fluid from a surgical wound,
• limb swelling,
• limb pain,
• kidney function disorders (may be observed in tests performed by a doctor),
• fever,
• stomach pain, indigestion, nausea or vomiting, constipation, diarrhoea,
• low arterial blood pressure (symptoms may include dizziness or fainting upon standing),
• general reduction in strength and energy (weakness, fatigue), headache, dizziness,
• rash, itching of the skin,
• increased activity of certain liver enzymes, which may be observed in blood test results.

Uncommon (may occur in up to 1 in 100 people)

• intracranial or cerebral hemorrhage (see signs of bleeding above),
• bleeding into a joint causing pain and swelling,
• thrombocytopenia (low platelet count, cells involved in blood clotting),
• allergic reactions, including allergic skin reactions,
• liver function disorders (may be observed in tests performed by a doctor),
• blood tests may show increased levels of bilirubin, increased activity of certain pancreatic or liver enzymes, or increased platelet count,
• fainting,
• malaise,
• rapid heartbeat,
• dry mouth,
• urticaria.

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

• muscle bleeding,
• cholestasis (bile stasis), hepatitis including liver cell damage,
• yellowing of the skin and eyes (jaundice),
• local swelling,
• accumulation of blood (hematoma) in the groin area as a complication of cardiac catheterization procedure when the catheter is inserted into an artery in the leg (pseudoaneurysm).

Frequency unknown (frequency cannot be estimated from available data)

• kidney failure following severe bleeding,
• bleeding in the kidneys, sometimes with presence of blood in urine, leading to impaired kidney function (drug-induced nephropathy associated with anticoagulant medicines),
• increased pressure in the muscles of the arms and legs following bleeding, which may lead to pain, swelling, altered sensation, tingling or paralysis (compartment syndrome following bleeding).

Reporting of adverse reactions
If you experience any adverse effects, including any not listed in this leaflet, you should inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:

Al. Jerozolimskie 181C,
02-222 Warsaw
tel.: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl

Adverse reactions may also be reported directly to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Varodoax

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and
each blister pack following "EXP". The expiry date refers to the last day of the stated month.
No special storage instructions are required for this medicine.
Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.
Medicines must not be disposed of via wastewater or household waste. You should ask
your pharmacist how to dispose of medicines no longer in use. This will help protect
the environment.

6. Contents of the package and other information

What Varodoax contains

• The active substance is rivaroxaban. Each tablet contains 2.5 mg of rivaroxaban.
• Other components are:
  Tablet core: microcrystalline cellulose, monohydrate lactose, sodium croscarmellose, hypromellose (E 5), sodium lauryl sulfate, magnesium stearate.
  Coating: Aqua Polish P white, composition: hypromellose (E 5), hypromellose (E 15), hydroxypropylcellulose, polyethylene glycol 8000, titanium dioxide (E 171).

What Varodoax looks like and contents of the pack
Varodoax 2.5 mg are white, round, biconvex coated tablets with a single-sided embossing "2.5".
The cardboard box contains: 28 film-coated tablets in blisters made of PVC/PVDC 90/Aluminum.

Marketing Authorization Holder
G.L. Pharma GmbH
Schlossplatz 1
8502 Lannach
Austria

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Poland
G.L. Pharma GmbH
Schlossplatz 1
8502 Lannach
Austria

For further information about this medicinal product, please contact the representative of the Marketing Authorization Holder:
G.L. PHARMA POLAND Sp. z o.o.
Al. Jana Pawła II 61/313
01-031 Warsaw
Tel: 022/ 636 52 23; 636 53 02
[email protected]