Package leaflet: Information for the user

Diwleiz, 15 mg, film-coated tablets
Diwleiz, 20 mg, film-coated tablets
Rivaroxaban
Please read all of this leaflet carefully 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, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

What Diwleiz is and what it is used for
What you need to know before taking Diwleiz
How to take Diwleiz
Possible side effects
How to store Diwleiz
Contents of the pack and other information

1. What Diwleiz is and what it is used for

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

prevent blood clots from forming in the brain (stroke) and in other blood vessels in the body, if the patient has an irregular heart rhythm called non-valvular atrial fibrillation.
treat blood clots in the deep 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.

Diwleiz 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 veins or in the blood vessels of the lungs, after at least 5 days of initial treatment with injectable medicines used for treating blood clots.

Diwleiz 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 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. stomach ulcer, trauma 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 if heparin is administered to maintain patency of a catheter in a vein or artery
if the patient has liver disease that leads to an increased risk of bleeding
if the patient is pregnant or breastfeeding. Diwleiz must not be used, and the doctor must be informed if the patient suspects that any of the above conditions apply.

Warnings and precautions
Before starting treatment with Diwleiz, discuss this with your doctor or pharmacist.
When to exercise special caution when using Diwleiz

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
- 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 patency of a catheter in a vein or artery (see section "Diwleiz 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 (backflow of stomach acid 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 eye (retinopathy)
- lung disease in which the bronchi are dilated and filled with pus (bronchiectasis) or previous bleeding from the lungs
in patients with prosthetic heart valves
if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing increased risk of blood clots), the patient should inform the doctor, who will decide whether a change in treatment is necessary
if the patient has abnormal blood pressure or is scheduled for surgery or other treatment aimed at removing a blood clot from the lungs.

If the patient suspects that any of the above conditions apply, the
doctor must be informed before using Diwleiz. The doctor will decide whether to use this medicine and whether the patient requires particularly close monitoring.
If the patient needs to undergo surgery

the doctor's instructions regarding the timing of taking Diwleiz before or after surgery must be strictly followed
if during surgery catheterization or spinal puncture (e.g. for epidural or spinal anaesthesia or pain relief) is planned:
- it is very important to take Diwleiz before and after the puncture or removal of the catheter according to the doctor's instructions
due to the need for special caution, the doctor must be informed immediately if numbness or weakness of the legs, or disturbances in bowel or bladder function occur after the anaesthesia wears off.

Children and adolescents
Diwleiz is not recommended for children weighing less than 30 kg.
There is insufficient data on the use of the medicine in children and adolescents for the indications approved in adults.
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
- oral ketoconazole (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 (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs)).

If the patient suspects that any of the above conditions apply, the
doctor must be informed before using Diwleiz, as the effect of Diwleiz 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 ulcer, preventive treatment for peptic ulcer disease may be prescribed.

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, the
doctor must be informed before using Diwleiz, as the effect of Diwleiz may be reduced. The doctor will decide whether to use Diwleiz and whether the patient requires particularly close monitoring.
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, the doctor must be informed immediately, who will decide on further treatment.
Driving and operating machinery
Diwleiz may cause dizziness (common side effect) or 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.
Diwleiz 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.
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 exactly as your doctor has instructed. If you are unsure,
you should consult your doctor or pharmacist.
Diwleiz 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 discuss alternative ways of taking
Diwleiz with their doctor. The tablet can be crushed and mixed with water or apple puree immediately
before administration. A meal should be taken promptly after this mixture.
If necessary, a crushed Diwleiz tablet may be administered via a gastric tube by a doctor.

How many tablets to take

Adults
- To prevent blood clots in the brain (stroke) and other blood vessels in the body:
  The recommended dose is one Diwleiz 20 mg tablet once daily. If the patient has kidney problems, the dose may be reduced to one Diwleiz 15 mg tablet once daily.
If the patient requires a procedure to open blocked blood vessels in the heart
(called percutaneous coronary intervention – PCI with stent placement), there is limited evidence
supporting dose reduction to one Diwleiz 15 mg tablet once daily (or one Diwleiz 10 mg tablet once
daily in case of impaired kidney function), in combination with an antiplatelet medicine such as
clopidogrel.
- For the 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 Diwleiz 15 mg tablet twice daily for the first 3 weeks.
  For treatment beyond 3 weeks, the recommended dose is one Diwleiz 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 Diwleiz 20 mg tablet once daily, the doctor
  may decide to reduce the dose after 3 weeks of treatment to one Diwleiz 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 Diwleiz 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:
  one Diwleiz 15 mg tablet once daily.
- Recommended dose for children and adolescents with a body weight of 50 kg or more:
  one Diwleiz 20 mg tablet once daily.

Each dose of Diwleiz should be taken with a meal and with a drink (e.g. water or juice).
Tablets should be taken every day at approximately the same time. It may help to set an alarm as a reminder.
Parents or caregivers should observe the child to ensure the full dose has been taken.

The dose of Diwleiz depends on body weight, so it is important to attend scheduled doctor’s appointments,
as dose adjustments may be necessary due to changes in weight.
Never adjust the dose of Diwleiz on your own. If necessary, your doctor will adjust the dose.
Do not split the tablet to achieve partial doses. If a lower dose is required, another formulation
containing rivaroxaban (oral suspension granules) should be used.
For children and adolescents who cannot swallow whole tablets, a rivaroxaban formulation in the form
of granules for oral suspension should be used.
If the oral suspension is not available, the rivaroxaban tablet may be crushed and mixed with water or
apple puree immediately before administration. A meal should be taken promptly after this mixture.
If necessary, a doctor may also administer the crushed tablet via a gastric tube.

If a dose is vomited or spat out

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

Contact your doctor if the patient repeatedly vomits or spits out the dose after taking Diwleiz.

When to take Diwleiz
Tablets should be taken every day until your doctor decides to stop treatment.
It is best to take the tablets at the same time each day, as this makes it easier to remember.
Your doctor will decide how long treatment should continue.
For prevention of blood clots in the brain (stroke) and other blood vessels in the body:
If heart rhythm needs to be restored by a procedure called cardioversion, Diwleiz should be taken
according to the timing advised by your doctor.

Missed dose of Diwleiz

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

Stopping Diwleiz treatment
Do not stop taking Diwleiz without first consulting your doctor, as Diwleiz 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, this medicine can cause adverse reactions, although not everyone will experience them.
As with other medicines with a similar action of reducing blood clot formation, Diwleiz may cause
bleeding, which potentially can 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 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, reduced level of consciousness, and neck stiffness. 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. The doctor may decide that very 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 disorders, and systemic involvement. The frequency of these adverse reactions is very rare (occurring in no more than 1 in 10,000 people).

Signs of severe allergic reactions

swelling of the face, lips, oral cavity, tongue, or throat; difficulty swallowing; 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 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 reactions in adults, children, and adolescents
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
gastrointestinal bleeding (including stomach or intestinal bleeding), genitourinary bleeding (including blood in urine and severe menstrual bleeding), nosebleeds, gum bleeding
bleeding into the eye (including conjunctival hemorrhage)
bleeding into tissues or body cavities (hematoma, bruising)
coughing up blood
bleeding from the skin 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, vomiting, constipation, diarrhea
low blood pressure (symptoms may include dizziness or fainting upon standing)
general decrease in strength and energy (weakness, fatigue), headache, dizziness
skin rash, itching
increased activity of certain liver enzymes, which may be evident 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, 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
dry mouth
urticaria

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

bleeding into muscles
cholestasis (bile stasis), hepatitis, including liver damage
yellowing of the skin and eyes (jaundice)
localized swelling
blood collection (hematoma) in the groin as a complication of cardiac catheterization procedure, when the catheter is inserted into the artery in the leg (pseudoaneurysm)

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

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

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 (anticoagulant-related nephropathy)
increased pressure within 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
In general, adverse reactions observed in children and adolescents treated with Diwleiz were
similar in type to those observed 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 in 10 people)

headache
fever
nosebleeds
vomiting

Common (may occur in no more than 1 in 10 people)

rapid heartbeat
blood tests may show increased levels of bilirubin (a bile pigment)
thrombocytopenia (low platelet count, blood cells that help in blood clotting)
excessive menstrual bleeding

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

blood tests 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 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 reactions can also be reported to the responsible entity.
By reporting adverse reactions, additional information on the safety of the medicine’s use can be
collected.

5. How to store the medicine Diwleiz

Keep this medicine out of the 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.
There are no special storage instructions 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 help protect the environment.

6. Contents of the pack and other information

What Diwleiz contains

The active substance is rivaroxaban. Each tablet contains 15 mg or 20 mg of rivaroxaban.
The other ingredients are:
Tablet core: lactose monohydrate, microcrystalline cellulose (PH 102), sodium croscarmellose, sodium lauryl sulphate, hypromellose 2910, magnesium stearate. See section 2 "Diwleiz contains lactose and sodium".
Tablet coating – 15 mg: hypromellose 2910 (E 464), iron oxide red (E 172), macrogol 4000 (E 1521), titanium dioxide (E 171), iron oxide black (E 172), iron oxide yellow (E 172).
Tablet coating – 20 mg: hypromellose 2910 (E 464), iron oxide red (E 172), titanium dioxide (E 171), macrogol 4000 (E 1521), iron oxide yellow (E 172).

What Diwleiz looks like and contents of the pack
Diwleiz 15 mg coated tablets are brown, round, biconvex, with engraved markings “M” on one side and “R2” on the other.
Available in:
aluminum blisters packed in cardboard boxes containing 14, 28, 56 or 98 coated tablets (with or without calendar blister), or in single-dose perforated blisters packed in cardboard boxes containing 28 x 1 coated tablet.

Diwleiz 20 mg coated tablets are brown, triangular, biconvex, with engraved markings “R” on one side and “20” on the other.
Available in:
aluminum blisters packed in cardboard boxes containing 14, 28, 56 or 98 coated tablets (with or without calendar blister), or in single-dose perforated blisters packed in cardboard boxes containing 28 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, PLA3000
Malta
MSN Labs Europe Limited
KW20A Corradino Park
Paola, PLA 3000
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Germany: Rivaroxaban MSN 15 mg Filmtabletten
ENR: 7008336
Rivaroxaban MSN 20 mg Filmtabletten
ENR: 7008337
Bulgaria: Дивлейз 15 mg филмирани таблетки
Дивлейз 20 mg филмирани таблетки
Czech Republic: Diwleiz
Hungary: Diwleiz 15 mg filmtabletta
Diwleiz 20 mg filmtabletta
Poland: Diwleiz
Romania: Diwleiz 15 mg comprimate filmate
Diwleiz 20 mg comprimate filmate
Slovakia: Diwleiz 15 mg
Diwleiz 20 mg