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.

You, as a user of this medicine, can help by reporting any side effects you experience after taking the medicine. For information on how to report side effects – see section 4.
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm someone else, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell 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

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 with 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 with body weight of 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 to form blood clots.

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 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 when heparin is administered to maintain catheter patency in a vein or artery,
• 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.
When to be especially careful when using Varodoax

• if the patient has an increased risk of bleeding, such as in the following conditions:
• severe kidney disease in adults and moderate to severe kidney disease in children and adolescents, as kidney function may affect the amount of drug 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 heparin is administered to maintain catheter patency in a vein or artery (see section "Varodoax and other medicines"),
• coagulation disorders,
• very high blood pressure that does not decrease despite treatment,
• stomach or intestinal diseases that may cause bleeding, e.g. inflammatory bowel disease or gastritis, or oesophagitis (inflammation of the oesophagus), e.g. due to gastro-oesophageal reflux disease (backflow of stomach acid into the oesophagus), or tumours located in the stomach, intestines, genital or urinary systems,
• 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 autoimmune disorder increasing the risk of thrombosis), the patient should inform the doctor, who will decide whether treatment adjustment is needed,
• if the patient has abnormal blood pressure or if surgery or another treatment to remove a pulmonary clot is planned.

If the patient suspects any of the above conditions apply, 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:

• 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 for 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 problems with bowel or bladder function occur, as immediate treatment may be 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 adult indications.
Varodoax and 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 increased. 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 ulcers, 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 remedy 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 her doctor immediately, who will decide on further treatment.
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 of sodium (23 mg) per tablet, which means the medicine is considered "sodium-free".

3. How to take Varodoax

This medicine should always be taken exactly as prescribed by your doctor. If you have any doubts, you should contact your doctor or pharmacist.

Varodoax should be taken with food.

The 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, a meal should be consumed promptly.

If necessary, a crushed Varodoax tablet may be administered through a gastric tube by a doctor.

How many tablets should be taken

• Adults

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

  If a 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 Varodoax 15 mg tablet once daily (or one Varodoax 10 mg tablet once daily in case of kidney impairment), used 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 to prevent recurrence of blood clots: The recommended dose is one Varodoax 15 mg tablet twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one Varodoax 20 mg tablet once daily. After at least 6 months of treatment for blood clots, the doctor may decide to continue treatment with either one 10 mg tablet once daily or one 20 mg tablet once daily. If the patient has kidney problems and is taking one Varodoax 20 mg tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one Varodoax 15 mg tablet 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 Varodoax 15 mg tablet once daily.
  • Recommended dose for children and adolescents with a body weight of 50 kg or more is one Varodoax 20 mg tablet 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 every day 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 yourself. If needed, your doctor will adjust the dose.

Do not split the tablet to achieve a lower dose. If a lower dose is required, a different medicine 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, a meal should be consumed. If necessary, the doctor may also administer the crushed tablet via a gastric tube.

If a dose is vomited or spit out

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

Contact your doctor if vomiting or spitting out the dose occurs repeatedly after taking Varodoax.

When to take Varodoax

The tablet(s) should be taken every day until your 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.

Your doctor will decide how long you should continue treatment.

Prevention of blood clots in the brain (stroke) and other blood vessels in the body:

If heart rhythm needs to be restored to normal rhythm using a cardioversion procedure, Varodoax should be taken at the time prescribed by your doctor.

Missed dose of Varodoax

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

Taking more than the recommended dose of Varodoax

If a patient has taken too many Varodoax tablets, they should contact their doctor immediately.

Taking too high a dose of Varodoax increases the risk of bleeding.

Stopping Varodoax treatment

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, please consult your doctor or pharmacist.

4. Possible adverse effects

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

As with other medicines with a similar mechanism of action that reduces blood clot formation, 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 are not always obvious or visible.

You should contact a doctor immediately if the patient or child experiences any of the following adverse effects:

• Signs of bleeding:

  • bleeding into the brain or inside the skull (symptoms may include headache, one-sided paralysis, vomiting, seizures, reduced 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 of the patient or a change in treatment is necessary.

• Signs of severe skin reactions:

  • widespread, acute skin rash, blistering or mucosal changes, e.g. in the mouth 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, mouth, 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 effects in adults, children and adolescents:

Common (may occur in up to 1 in 10 people)

• reduced number of red blood cells, which may cause paleness of the skin and lead to weakness or shortness of breath,
• gastrointestinal bleeding or intestinal bleeding, bleeding from the urinary or genital tract (including blood in urine and severe menstrual bleeding), nosebleeds, bleeding from gums,
• ocular bleeding (including bleeding from the sclera 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 (feeling sick) or vomiting, constipation, diarrhoea,
• low blood pressure (symptoms may include dizziness or fainting upon standing),
• general loss of strength and energy (weakness, fatigue), headache, dizziness,
• rash, skin itching,
• increased activity of certain liver enzymes, which may be evident in blood test results.

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

• bleeding into the brain or inside the skull (see signs of bleeding above),
• bleeding into a joint 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 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 1000 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 as a complication of cardiac catheterization 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 blood in urine, leading to impaired kidney function (drug-induced anticoagulant-associated nephropathy),
• increased pressure in the muscles of arms and legs after bleeding, which may cause pain, swelling, altered sensation, tingling or paralysis (compartment syndrome following bleeding).

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

Adverse effects observed more frequently in children and adolescents:

Very common (may occur more frequently than in 1 in 10 people)

• headache
• fever
• nosebleeds
• vomiting

Common (may occur in up to 1 in 10 people)

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

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

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

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can also be reported directly to the Department of Monitoring Adverse Effects of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:

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

Adverse effects may also be reported to the marketing authorization holder.

Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Varodoax

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and
on each blister after "EXP". The expiry date refers to the last day of the stated month.
No special storage instructions apply 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 required. Such measures 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.
• Other ingredients are:
  Core of the tablet: 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), hydroxypropylcellulose, 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 monogram "15" embossed on one side.
Varodoax 20 mg are brick-red, round, biconvex coated tablets with a monogram "20" embossed on one side.
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 further information about this medicine, please contact 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]