Rivahib

Package leaflet: Information for the patient

Varodoax, 15 mg, film-coated tablets
Varodoax, 20 mg, film-coated tablets
Rivaroxabanum
This medicinal product will be subject to additional monitoring. This will allow any new safety information to be identified quickly.

Patients can help by reporting any suspected adverse reactions that occur after using the medicine. For information on how to report adverse reactions – see section 4.
It is important to read this leaflet before taking the medicine, as it contains important information for the patient.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not give it to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Varodoax is and what it is used for
2. What you need to know 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

Varodoax contains the active substance rivaroxaban.
Varodoax is used in adults to:

• prevent the formation of blood clots in the brain (stroke) and in other blood vessels of the body in patients who have a type of irregular heartbeat known as non-valvular atrial fibrillation.
• 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 recurrence of blood clots in the blood vessels of the legs and/or lungs.

Varodoax is used in children and adolescents under 18 years of age and weighing 30 kg or more to:

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

Varodoax 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 using 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 excessive 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 when heparin is administered to maintain the patency of a venous or arterial catheter,
• if the patient has a liver disease that leads to an increased 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 treatment with Varodoax, discuss this with your doctor or pharmacist.
When to exercise special caution when using Varodoax

• if the patient has an increased risk of bleeding, such as in the following conditions:
• severe kidney disease in adults, or moderate to severe kidney disease in children and adolescents, as kidney function may affect the amount of medicine acting in the patient's body,
• if the patient is taking other anticoagulant medicines (e.g. warfarin, dabigatran, apixaban or heparin), except when switching anticoagulant therapy or when heparan is administered to maintain the patency of a venous or arterial catheter (see section "Varodoax with other medicines"),
• coagulation disorders,
• very high blood pressure that does not decrease despite medication,
• stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the stomach or intestines or oesophagitis (throat and oesophagus), e.g. due to gastro-oesophageal reflux disease (acid reflux into the oesophagus), or tumours located in the stomach, intestines, genital or urinary system,
• vascular disease of the posterior part of the eye (retinopathy),
• lung disease with bronchiectasis (dilated bronchi filled with pus) or previous pulmonary haemorrhage,
• in patients with prosthetic heart valves,
• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing increased risk of thrombosis), the patient should inform the doctor, who will decide whether treatment adjustment is necessary,
• if the patient has abnormal blood pressure or is scheduled for surgery or other treatment aimed at removing a pulmonary embolism.

If the patient suspects any of the above conditions, they should inform the doctor before using Varodoax. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the patient needs to undergo surgery:

• it is essential to strictly follow the doctor's instructions regarding the timing of Varodoax administration before or after surgery,
• if during surgery a lumbar puncture or placement of a catheter into the spinal canal is planned (e.g. for epidural or spinal anaesthesia or pain relief):
• it is very important to take Varodoax before and after the puncture or catheter removal, as directed by the doctor,
• the patient should immediately inform the doctor if, after the anaesthesia ends, symptoms such as numbness, leg weakness, or disturbances in bowel or bladder function occur, as immediate treatment is required.

Children and adolescents
Varodoax tablets are not recommended for children weighing less than 30 kg.
There is insufficient data on the use of Varodoax in children and adolescents for the indications approved in adults.

Varodoax with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription.

• If the patient is taking:
• certain antifungal medicines (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are 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),
• anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid),
• dronedarone, a medicine used to treat heart rhythm disorders,
• certain antidepressants (selective serotonin reuptake inhibitors (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)).

If the patient suspects any of the above apply, they should inform the doctor before using 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 that the patient has an increased risk of developing gastric or duodenal ulceration, they may prescribe preventive treatment for peptic ulcer disease.

• If the patient is taking:
• certain antiepileptic medicines (phenytoin, carbamazepine, phenobarbital),
• St John's wort (Hypericum perforatum), a herbal medicine used for depression,
• rifampicin, an antibiotic.

If the patient suspects any of the above apply, they should inform the doctor before using 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 should inform the doctor immediately, who will decide on further management.

Driving and operating machinery
Varodoax may cause dizziness (common side effects) and fainting (uncommon side effects) (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, they should consult their doctor before taking this medicine.
The medicine contains less than 1 mmol sodium (23 mg) per tablet, which means the medicine is considered "sodium-free".

3. How to take Varodoax

This medicine should always be taken as prescribed by your doctor. If you have any doubts, you should
contact your doctor or pharmacist.
Varodoax should be taken with food.
Tablet(s) should be swallowed whole, preferably with water.
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. After taking this mixture, the patient should immediately eat a meal.
If necessary, a crushed Varodoax tablet may be administered through a gastric tube.
How many tablets should be taken

• Adults
• For prevention of blood clots in the brain (stroke) and in other blood vessels in the body: The recommended dose is one tablet of Varodoax 20 mg once daily. If the patient has kidney problems, the dose may be reduced to one tablet of Varodoax 15 mg once daily.

If the patient requires a procedure to unblock blood vessels in the heart
(called percutaneous coronary intervention – PCI with stent placement), there is
limited evidence supporting dose reduction to one tablet of Varodoax 15 mg once daily
(or one tablet of Varodoax 10 mg once daily in patients with kidney impairment) in
combination with an antiplatelet medicine such as clopidogrel.

• For treatment of blood clots in the veins of the legs, blood clots in the blood vessels of the lungs, and for prevention of recurrence of blood clots: The recommended dose is one tablet of Varodoax 15 mg twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one tablet of Varodoax 20 mg once daily. After at least 6 months of treatment for blood clots, the doctor may decide to continue treatment with either one tablet of 10 mg once daily or one tablet of 20 mg once daily. If the patient has kidney impairment and is taking one tablet of Varodoax 20 mg once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one tablet of Varodoax 15 mg once daily, if the risk of bleeding is greater than the risk of further blood clots.
• Children and adolescents The dose of Varodoax depends on body weight and will be calculated by the doctor.
• Recommended dose for children and adolescents with a body weight from 30 kg to below 50 kg is one tablet of Varodoax 15 mg once daily.
• Recommended dose for children and adolescents with a body weight of 50 kg or more is one tablet of Varodoax 20 mg once daily.

Each dose of Varodoax should be taken with a meal, accompanied by a drink (e.g. water or juice). Tablets should be taken daily at approximately the same time. Consider setting an alarm to remind you.
For parents or caregivers: You should observe the child to ensure they have taken the full dose.
The dose of Varodoax depends on body weight, so it is important to attend scheduled doctor’s appointments, as dose adjustments may be necessary due to changes in body weight.
Never adjust the dose on your own. If needed, the doctor will adjust the dose.
Do not split the tablet to achieve a lower dose. If a lower dose is required, a different medicinal product containing rivaroxaban in the form of granules for oral suspension should be used.
For children and adolescents who are unable to swallow whole tablets, a different medicinal product containing rivaroxaban in the form of granules for oral suspension should be used.
If the oral suspension is not available, the Varodoax tablet may be crushed and mixed with water or apple puree immediately before administration. After taking this mixture, the patient should immediately eat a meal. If necessary, the doctor may also administer the crushed tablet via a gastric tube.
If a dose is vomited or spat out

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

Contact your doctor if the patient repeatedly spits out the dose or vomits after taking Varodoax.
When to take Varodoax
The tablet(s) should be taken every day until the doctor decides to stop treatment.
It is best to take the tablet(s) at the same time each day, as this makes it easier to remember.
The doctor will decide how long the patient should continue treatment.
Prevention of blood clots in the brain (stroke) and in other blood vessels in the body:
If restoration of normal heart rhythm is required using a procedure called cardioversion, Varodoax should be taken as directed by the doctor.
Missed dose of Varodoax

• Adults, children and adolescents: If the patient takes one tablet of 20 mg or one tablet of 15 mg once daily and a dose is missed, take the tablet as soon as possible. Do not take more than one tablet in one day to make up for the missed dose. Take the next tablet the following day, then continue taking one tablet once daily.
• Adults: If the patient takes one tablet of 15 mg twice daily and a dose is missed, take the tablet as soon as possible. Do not take more than two tablets of 15 mg in one day. If the patient forgot to take a dose, they may take two tablets of 15 mg at the same time to achieve a total of two tablets (30 mg) taken within one day. The next day, continue taking one tablet of 15 mg twice daily.

Taking more than the recommended dose of Varodoax
If the patient has taken too many Varodoax tablets, contact a doctor immediately.
Taking too high a dose of Varodoax increases the risk of bleeding.
Stopping treatment with Varodoax
Do not stop taking Varodoax without first consulting your doctor, as Varodoax treats and prevents serious medical conditions.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, Varodoax may cause adverse reactions, although not everyone experiences them.

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

If you or your child experience any of the following adverse reactions, contact a doctor immediately:

• Signs of bleeding:
  • bleeding into the brain or inside the skull (symptoms may include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness. This is a serious medical emergency. Seek immediate medical help!),
  • prolonged or excessive bleeding,
  • unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain, or angina. The doctor may decide that close monitoring or a change in treatment is necessary.
• Signs of severe skin reactions:
  • widespread, acute skin rash, blistering, or lesions on mucous membranes such as the tongue or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • drug reaction with eosinophilia and systemic symptoms (DRESS), characterized by rash, fever, internal organ inflammation, hematological abnormalities, 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, mouth, tongue, or throat; hives and difficulty breathing; 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 in adults, children, and adolescents:
Common (may occur in 1 out of 10 people)

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

Uncommon (may occur in 1 out of 100 people)

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

Rare (may occur in 1 out of 1,000 people)

• bleeding into muscles,
• cholestasis (bile stasis), liver inflammation 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 when the catheter is inserted into an artery in the leg (pseudoaneurysm).

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

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

Adverse reactions in children and adolescents
In general, adverse reactions observed in children and adolescents treated with Varodoax were similar in type to those seen in adults and were mostly mild to moderate in severity.

Adverse reactions observed more frequently in children and adolescents:
Very common (may occur in more than 1 out of 10 people)

• headache
• fever
• nosebleeds
• vomiting

Common (may occur in 1 out of 10 people)

• rapid heartbeat
• blood test results may show increased bilirubin levels (a yellow pigment)
• thrombocytopenia (low platelet count, the blood cells that help with clotting)
• excessive menstrual bleeding

Uncommon (may occur in 1 out of 100 people)

• blood test results may show increased levels of a subcategory of bilirubin (direct bilirubin, a yellow pigment).

Reporting of adverse reactions
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 to the responsible entity.

By reporting adverse reactions, more information on the safety of the medicine can be collected.

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 after "EXP". The expiry date refers to the last day of the stated month.
No special storage conditions 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. Ask your
pharmacist how to dispose of medicines no longer in use. This will help protect
the environment.

6. Contents of the pack and other information

What Varodoax contains

• The active substance is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.
• The other ingredients are:
  Tablet core: microcrystalline cellulose, lactose monohydrate, sodium croscarmellose, hypromellose (E 5), sodium lauryl sulfate, magnesium stearate.
  Coating: Aqua Polish P white [composition: hypromellose (E 5), hypromellose (E 15), hydroxypropyl cellulose, polyethylene glycol 8000, titanium dioxide (E 171)], iron oxide red (E 172).

What Varodoax looks like and contents of the pack
Varodoax 15 mg are pink, round, biconvex coated tablets with a single-sided embossing of „15”.
Varodoax 20 mg are brick-red, round, biconvex coated tablets with a single-sided embossing of „20”.
Cartons contain 14 or 28 film-coated tablets in PVC/PVDC 90/Aluminium blisters.

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

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

For more detailed information about this medicine, please contact the representative of the Marketing Authorisation 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]