Rivanoptim

Package leaflet: Information for the user

Rivanoptim, 15 mg, coated tablets
Rivanoptim, 20 mg, coated tablets
Rivaroxaban
Please read the entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• Ask your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

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

1. What Rivanoptim is and what it is used for

Rivanoptim contains the active substance rivaroxaban and is used in adults to:

• prevent the formation of blood clots in the brain (stroke) and other blood vessels in the body in patients with a type of irregular heartbeat called 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 veins of the legs and/or lungs.

Rivanoptim 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 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. Rivanoptim 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 Rivanoptim

When not to take Rivanoptim

• if the patient is allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6)

• if the patient is experiencing excessive bleeding

• if the patient has a disease or condition of an organ that leads to an increased risk of serious bleeding (e.g. stomach ulcer, injury or bleeding into the brain, recent surgery on the brain or eyes)

• if the patient is taking other medicines that prevent blood clots (e.g. warfarin,
  dabigatran, apixaban or heparin), except when switching anticoagulant therapy or
  when heparin is administered to maintain the patency of a catheter in a vein or artery

• 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 Rivanoptim, and also inform the doctor if the patient suspects that any of the above circumstances apply. Warnings and precautions Before starting to take Rivanoptim, consult a doctor or pharmacist.

When to exercise particular caution when taking Rivanoptim

• if the patient has an increased risk of bleeding, such as in the following conditions:
• severe kidney disease in adults, and moderate or severe kidney disease in children and adolescents, 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 the patency of a catheter in a vein or artery (see section "Rivanoptim with other medicines")
• bleeding disorders
• very high blood pressure that does not decrease despite medication
• stomach or intestinal diseases that may cause bleeding, e.g. inflammation of the intestines and stomach or inflammation of the oesophagus (throat and oesophagus), e.g. due to gastro-oesophageal reflux disease (acid reflux into the oesophagus), or tumours located in the stomach or intestines, or in the genital or urinary system
• blood vessel disease in the back of the eyeball (retinopathy)
• lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding
• in patients with heart valve prostheses
• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing an increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment needs to be changed
• if the patient has been diagnosed with abnormal blood pressure or is scheduled for surgery or other treatment aimed at removing a pulmonary embolism. If the patient suspects that any of the above conditions apply, they should inform the doctor before taking Rivanoptim. 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 taking Rivanoptim before or after surgery.
• if catheterisation or spinal puncture (e.g. for epidural or spinal anaesthesia or pain relief) is planned during surgery: it is very important to take Rivanoptim before and after the puncture or catheter removal, as directed by the doctor
• due to the need for special caution, the doctor should be informed immediately if numbness or weakness in the legs, or disturbances in bowel or bladder function occur after the anaesthesia ends.

Children and adolescents
Rivanoptim tablets are not recommended for children weighing less than 30 kg.
There is insufficient data on the use of Rivanoptim in children and adolescents for the indications approved in adults.
Rivanoptim 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 medicines used to treat depression (selective serotonin reuptake inhibitors (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)) If the patient suspects that any of the above conditions apply, they should inform the doctor before taking Rivanoptim, as the effect of Rivanoptim may be enhanced when taken together with the above-mentioned medicines. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring. If the doctor considers that the patient is at increased risk of developing stomach or duodenal ulcers, they may prescribe treatment to prevent peptic ulcer disease.
• If the patient is taking
• certain medicines used to treat epilepsy (phenytoin, carbamazepine, phenobarbital)
• St John's wort (Hypericum perforatum), a herbal remedy used for depression
• rifampicin, which belongs to the group of antibiotics

If the patient suspects that any of the above conditions apply, they should inform the doctor
before taking Rivanoptim, as the effect of Rivanoptim may be reduced when taken together with the above-mentioned medicines. The doctor will decide whether to use Rivanoptim and whether the patient requires particularly close monitoring.
Pregnancy and breastfeeding
Do not use Rivanoptim 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 Rivanoptim. If the patient becomes pregnant while taking Rivanoptim, they should inform the doctor immediately, who will decide on further treatment.
Driving and operating machinery
Rivanoptim 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.
Rivanoptim contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult a doctor before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to take Rivanoptim

This medicine should always be taken exactly as directed by your doctor. If in doubt, consult your doctor or pharmacist.
Rivanoptim should be taken with food.
The tablet(s) should be swallowed whole, preferably with water.
If a patient has difficulty swallowing the whole tablet, discuss alternative ways of taking Rivanoptim with your doctor. The tablet may be crushed and mixed with water or soft food such as apple puree immediately before administration. After taking this mixture, a meal should be consumed promptly.
If necessary, a doctor may administer crushed Rivanoptim tablets through a gastric tube.

How many tablets to take

Adults

• For prevention of blood clots in the brain (stroke) and in other blood vessels throughout the body: The recommended dose is one Rivanoptim 20 mg tablet once daily. If the patient has kidney problems, the dose may be reduced to one Rivanoptim 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 Rivanoptim 15 mg tablet once daily (or one Rivanoptim 10 mg tablet once daily in case of impaired kidney function), in combination with an antiplatelet medicine such as clopidogrel.

• For treatment of blood clots in the leg veins, blood clots in the blood vessels of the lungs, and prevention of recurrence of blood clots: The recommended dose is one Rivanoptim 15 mg tablet twice daily for the first 3 weeks. After 3 weeks of treatment, the recommended dose is one Rivanoptim 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 Rivanoptim 20 mg tablet once daily, the doctor may decide to reduce the dose after 3 weeks of treatment to one Rivanoptim 15 mg tablet once daily, if the risk of bleeding is greater than the risk of forming further blood clots.

Children and adolescents
The dose of Rivanoptim depends on body weight and will be calculated by the doctor.

• Recommended dose for children and adolescents with a body weight of 30 kg to less than 50 kg is one tablet of Rivanoptim 15 mg once daily.
• Recommended dose for children and adolescents with a body weight of 50 kg or more is one tablet of Rivanoptim 20 mg once daily.

Each dose of Rivanoptim should be taken with a meal and with a drink (e.g. water or juice). Tablets should be taken daily at approximately the same time. Consider setting an alarm as a reminder. For parents or caregivers: observe the child to ensure the full dose has been taken.

The dose of Rivanoptim depends on body weight, so it is important to attend scheduled doctor’s appointments, as dose adjustments may be needed due to changes in weight. Never adjust the dose independently. If necessary, the doctor will adjust the dose.
Do not split tablets to achieve partial doses. If a lower dose is required, other pharmaceutical forms such as granules for oral suspension may be more appropriate. For children and adolescents who cannot swallow whole tablets, rivaroxaban in the form of granules for oral suspension should be used.
If the oral suspension is not available, the Rivanoptim 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, a doctor may also administer crushed Rivanoptim tablets through a gastric tube.

If a dose is vomited or spit out

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

Contact your doctor if there are repeated episodes of vomiting or spitting out the dose after taking Rivanoptim.

When to take Rivanoptim
Tablets 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 heart rhythm needs to be restored by a procedure called cardioversion, Rivanoptim should be taken as directed by the doctor.

Missed dose of Rivanoptim

• Adults, children and adolescents: If the patient takes one 20 mg tablet or one 15 mg tablet 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 15 mg tablet twice daily and a dose is missed, 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, resume taking one 15 mg tablet twice daily.

Taking more than the recommended dose of Rivanoptim
If a patient has taken too many Rivanoptim tablets, contact a doctor immediately. Taking too high a dose of Rivanoptim increases the risk of bleeding.

Stopping Rivanoptim
Do not stop taking Rivanoptim without first consulting your doctor, as Rivanoptim 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 any medicine, Rivanoptim may cause adverse reactions, although not everyone experiences them.
Like other medicines with a similar mechanism of action that reduce blood clot formation, Rivanoptim may cause bleeding, which potentially could be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). Signs of bleeding are not always obvious or visible.
Immediately inform a doctor if the patient or the patient's child experiences any of the following adverse reactions:
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. A serious, sudden 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. The doctor may decide that close monitoring of the patient or a change in treatment is necessary.

Signs of severe skin reactions:

• Extensive, acute skin rash, blistering, or mucosal lesions, 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 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, 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 in adults, children, and adolescents:
Common (may occur in 1 out of 10 people)

• Decrease 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 severe menstrual bleeding), nosebleeds, bleeding from gums
• Bleeding into the eye (including bleeding from the conjunctiva)
• 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, vomiting, constipation, diarrhea
• Low blood pressure (symptoms may include dizziness or fainting upon standing)
• General lack of strength and energy (weakness, fatigue), headache, dizziness
• Rash, itching of the skin
• Increased activity of certain liver enzymes, which may be seen in blood test results.

Uncommon (may occur in 1 out of 100 people)

• Bleeding into the brain or within the skull (see signs of bleeding above)

• Bleeding into joints causing pain and swelling

• Thrombocytopenia (low platelet count, blood 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

• Dryness in the mouth

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

• Bleeding into muscles

• Cholestasis (bile stasis), hepatitis including liver cell damage

• Yellowing of the skin and eyes (jaundice)

• Localized swelling

• Blood collection (hematoma) in the groin as a complication of cardiac catheterization when the catheter is inserted into an artery in the leg (pseudoaneurysm).

Very rare (may occur in 1 out of 10,000 people)

• Accumulation of eosinophils, a type of white granulocytic blood cells, causing lung inflammation (eosinophilic pneumonia).

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

• Kidney failure following severe bleeding
• Bleeding in the kidneys, sometimes with blood in urine, leading to impaired kidney function (anticoagulant-related nephropathy)
• Increased pressure in the muscles of arms and legs following bleeding, which may lead to pain, swelling, altered sensation, numbness, or paralysis (compartment syndrome following bleeding).

Adverse reactions in children and adolescents
Generally, adverse reactions observed in children and adolescents treated with Rivanoptim were similar in type to those observed in adults and were mainly 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 bile pigment)
• Thrombocytopenia (low platelet count, blood cells that help in blood 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 bile pigment).

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform a doctor or pharmacist. 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, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Rivanoptim

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and on each blister or bottle: EXP. The expiry date refers to the last day of the stated month.
Tablets 15 mg in blisters: Do not store above 30°C.
Tablets 15 mg in containers and tablets 20 mg in blisters and in containers: This medicine does not require any special storage conditions.
Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Rivanoptim contains

• The active substance is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.
• The other ingredients are:
  Tablet core: monohydrate lactose, powdered cellulose, crospovidone type A, crospovidone type B, copovidone, sodium lauryl sulfate, colloidal anhydrous silica, magnesium stearate. See section 2, "Rivanoptim contains lactose and sodium".
  Tablet coating: polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc, iron oxide red (E 172).

What Rivanoptim looks like and contents of the pack

Rivanoptim 15 mg coated tablets are red, round, biconvex (7 mm in diameter), with the imprint 'C03' on one side. The tablets are contained in:

• Blister packs in cardboard boxes containing 14, 28, 42 or 100 coated tablets, or
• Bottles containing 100 coated tablets.

Rivanoptim 20 mg coated tablets are dark red, round, biconvex (8 mm in diameter), with the imprint 'C04' on one side. The tablets are contained in:

• Blister packs in cardboard boxes containing 14, 28 or 100 coated tablets, or
• Bottles containing 100 coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Synoptis Pharma Sp. z o.o.
ul. Krakowiaków 65
02-255 Warsaw
Tel. 607 696 231
e-mail: [email protected]

Manufacturer
Coripharma ehf.
Reykjavikurvegur 78-80
220 Hafnarfjörður
Iceland
Email: [email protected]
Tel: +354 4206700

This medicinal product is authorised in the member states of the European Economic Area under the following names:
Iceland: Rivaroxaban Coripharma
Poland: Rivanoptim