Diwleiz

Package leaflet: Information for the user

Diwleiz, 2.5 mg, coated tablets
Rivaroxabanum
Please read this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist immediately. See section 4.

Table of contents

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

1. What Diwleiz is and what it is used for

The patient has been prescribed Diwleiz because:

• they 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. Diwleiz reduces, in adults, the risk of further heart attacks or the risk of death due to heart- or blood vessel-related disease. Diwleiz will not be given to the patient as the only treatment. The doctor will also prescribe:
  • acetylsalicylic acid, or
  • acetylsalicylic acid and clopidogrel or ticlopidine.

or

• they are at high risk of blood clots due to coronary artery disease or peripheral arterial disease causing symptoms. Diwleiz reduces, in adults, the risk of blood clots (atherosclerotic thrombotic events). Diwleiz will not be given to the patient as the only treatment. The doctor will also prescribe acetylsalicylic acid. In some cases, if the patient is receiving Diwleiz after a procedure to unblock a narrowed or blocked artery in the lower limb to restore blood flow, the doctor may additionally prescribe clopidogrel for a short period alongside acetylsalicylic acid.

Diwleiz 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 to form blood clots.

2. Information before using Diwleiz

When not to use Diwleiz

• 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. gastric ulcer, trauma or bleeding into the brain, recent surgery on the brain or eyes)
• if the patient is taking other medicines that prevent blood clotting (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 has previously experienced bleeding or a blood clot in the brain (stroke)
• if the patient has been diagnosed with coronary artery disease or peripheral arterial disease and has previously had bleeding in the brain (hemorrhagic stroke), blockage of small arteries supplying blood to tissues in deep brain structures (sinus thrombosis), or if the patient has had a blood clot in the brain (ischemic, non-sinus stroke) within the last month
• 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 Diwleiz and inform your doctor if the patient suspects that any of the above circumstances apply.
Warnings and precautions
Before starting treatment with Diwleiz, discuss this with your doctor or pharmacist.
Diwleiz should not be used in combination with anticoagulant medicines other than acetylsalicylic acid, clopidogrel or ticlopidine, such as prasugrel or ticagrelor.
When to exercise special caution with Diwleiz

• if the patient has an increased risk of bleeding, such as in the following conditions:
• moderate or severe kidney disease, as kidney function may affect the amount of medicine acting in the patient's body
• if the patient is taking other medicines that prevent blood clotting (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 (see section "Diwleiz with other medicines")
• coagulation disorders
• very high blood pressure that does not decrease despite medication
• diseases of the stomach or intestines that may cause bleeding, e.g. inflammation of the intestines and stomach or esophagus (throat and esophagus), e.g. due to gastroesophageal reflux disease (backflow of stomach acid into the esophagus), or tumors located in the stomach, intestines, genital or urinary system
• blood vessel disease of the posterior part of the eyeball (retinopathy)
• lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous lung bleeding
• if the patient is over 75 years old
• if the patient weighs less than 60 kg
• if the patient has coronary artery disease with severe symptomatic heart failure
• in patients with prosthetic heart valves
• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing an increased risk of clot formation), the patient should inform the doctor, who will decide whether a change in treatment is necessary.

If the patient suspects that any of the above conditions apply, the patient should inform the
doctor before using Diwleiz. The doctor will decide whether to use this medicine and whether the
patient should be placed under particularly close observation.
If the patient needs to undergo surgery

• it is essential to strictly follow the doctor's instructions regarding taking Diwleiz at a specific time before or after surgery.
• If during a surgical procedure a lumbar puncture or placement of a spinal catheter is planned for the patient (e.g. for epidural or intrathecal anesthesia or for pain relief):
• it is very important to take Diwleiz before and after the puncture or removal of the catheter, 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 anesthesia ends.

Children and adolescents
Diwleiz 2.5 mg tablets are not recommended for patients under 18 years of age. There is
insufficient data on the use of the medicine in children and adolescents.
Diwleiz 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 - a condition 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 medicines used to treat depression (selective serotonin reuptake inhibitors (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)).

If any of the above situations apply to the patient, tell the
doctor before using Diwleiz, as the effect of Diwleiz may be enhanced. The doctor will decide whether to use this medicine and whether the patient should be placed under particularly close observation.
If the doctor considers that the patient has an increased risk of developing stomach or intestinal ulcers, preventive treatment may be initiated.

• If the patient is taking
• certain medicines used to treat epilepsy (phenytoin, carbamazepine, phenobarbital)
• St. John's wort ( Hypericum perforatum ), a herbal medicine used for depression
• rifampicin, which belongs to the group of antibiotics. If any of the above situations apply to the patient, tell the doctor before using Diwleiz, as the effect of Diwleiz may be reduced. The doctor will decide whether to use Diwleiz and whether the patient should be placed under particularly close observation.

Pregnancy and breastfeeding
Do not use Diwleiz 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 Diwleiz. If the patient becomes pregnant while taking this medicine, she should inform the doctor immediately, who will decide on further treatment.
Driving and operating machinery
Diwleiz may cause dizziness (common side effects) or 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.
Diwleiz contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should contact the doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Diwleiz

This medicine should always be taken as directed by the doctor. In case of doubt, consult the doctor or pharmacist.
How many tablets to take
The recommended dose is one 2.5 mg tablet twice daily. Diwleiz should be taken at approximately the same time each day (for example, one tablet in the morning and one in the evening). This medicine may be taken with or without food.
If the patient has difficulty swallowing the whole tablet, discuss alternative ways of taking Diwleiz with the doctor. The tablet may be crushed and mixed with water or apple puree immediately before administration. If necessary, the doctor may administer crushed Diwleiz tablets via a gastric tube.
Diwleiz will not be given to the patient as the only medication.
The doctor will also advise the patient to take acetylsalicylic acid.
If the patient is receiving Diwleiz following an acute coronary syndrome, the doctor may also prescribe clopidogrel or ticlopidine.
If the patient is receiving Diwleiz after a revascularization procedure of a narrowed or blocked artery in the lower limb to restore blood flow, the doctor may additionally prescribe clopidogrel for a short period alongside acetylsalicylic acid.
The doctor will inform the patient of the exact dosage (usually 75–100 mg acetylsalicylic acid daily, 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 Diwleiz
Treatment with Diwleiz after 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 Diwleiz 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 Diwleiz
If the patient has taken more than the recommended dose of Diwleiz, contact the doctor immediately. Taking too high a dose of Diwleiz increases the risk of bleeding.
Missed dose of Diwleiz
Do not take a double dose to make up for a missed dose. If a dose has been missed, the patient should take the next dose at the scheduled time.
Stopping Diwleiz
Diwleiz should be taken regularly and for the duration recommended by the doctor.
Do not stop taking Diwleiz without first consulting the doctor. Stopping this medicine may increase the risk of another heart attack, stroke, or death due to heart or blood vessel disease.
If there are any further doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse effects

Like any medicine, Diwleiz may cause adverse effects, although not everyone experiences them.
Like other medicines with a similar blood-thinning effect, Diwleiz 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 immediately inform your doctor if any of the following adverse effects occur:

• 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 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. 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., in the mouth or eyes (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• drug reaction causing rash, fever, internal organ inflammation, hematological disorders, and systemic illness (DRESS syndrome). The frequency of these adverse effects is very rare (occurring in no more than 1 in 10,000 people).
• Signs of severe allergic reactions
• swelling of the face, lips, mouth, oral cavity, tongue, or throat; difficulty swallowing; hives 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 no more than 1 in 10,000 people) and uncommon (angioedema and allergic edema; may occur in no more than 1 in 100 people).

General list of possible adverse effects
Common (may occur in no more than 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
• 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 white part of the eye)
• bleeding into tissues or body cavities (hematoma, bruising)
• coughing up blood
• bleeding from the skin or under the skin
• 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, diarrhea
• low blood pressure (symptoms may include dizziness or fainting upon standing)
• general decrease in strength and energy (weakness, fatigue), headache, dizziness
• rash, itchy skin
• increased activity of certain liver enzymes, which may be seen in blood test results

Uncommon (may occur in no more than 1 in 100 people)

• bleeding into the brain or inside the skull (see above, signs of bleeding)
• 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
• hives

Rare (may occur in no more than 1 in 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 no more than 1 in 10,000 people):

• accumulation of eosinophils, a type of granular white 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 cause pain, swelling, altered sensation, numbness, or paralysis (compartment syndrome following bleeding).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects 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 effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Diwleiz

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on each blister or bottle 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 the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Diwleiz contains

• The active substance is rivaroxaban. Each tablet contains 2.5 mg of rivaroxaban.

• Other components are:
  Tablet core: Lactose monohydrate, microcrystalline cellulose (PH 102), sodium croscarmellose, sodium lauryl sulfate, hypromellose 2910, magnesium stearate. See section 2 "Diwleiz contains lactose and sodium".

  Tablet coating: Hypromellose 2910 (E 464), titanium dioxide (E 171), macrogol 4000 (E 1521), iron oxide yellow (E 172).

What Diwleiz looks like and contents of the pack
Diwleiz 2.5 mg coated tablets are yellow, round, biconvex, with an embossed marking "M" on one side and "R" on the other side.

Available in:

• Blister packs contained in cardboard boxes of 28, 56, 98 or 196 coated tablets (with or without calendar blister), or
• Perforated single-dose blisters packed in cardboard boxes containing 56 x 1 coated tablet.

Not all pack sizes may be marketed.

Marketing Authorisation Holder:
MSN Labs Europe Limited
KW20A Corradino Park
Paola, PLA 3000
Malta
Tel.: (+48) 699 711 147

Manufacturer/Importer:
Pharmadox Healthcare Limited
KW20A Kordin Industrial Estate
Paola, PLA 3000
Malta
MSN Labs Europe Limited
KW20A Corradino Park
Paola, PLA 3000
Malta

This medicinal product is authorised in the European Economic Area under the following names:
Germany: Rivaroxaban MSN 2.5 mg Filmtabletten
ENR: 7008334
Bulgaria: Дивлейз 2,5 mg филмирани таблетки
Czech Republic: Diwleiz
Hungary: Diwleiz 2.5 mg filmtabletta
Poland: Diwleiz
Romania: Diwleiz 2.5 mg comprimate filmate
Slovakia: Diwleiz 2.5 mg