Evrenzo

Package leaflet: Information for the patient

Evrenzo 20 mg film-coated tablets, 50 mg film-coated tablets, 70 mg film-coated tablets, 100 mg film-coated tablets, 150 mg film-coated tablets

roxadustat
Please read this leaflet carefully before you start taking this medicine, as it contains
important information for you.

• 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 only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4. Contents of this leaflet
  1. What Evrenzo is and what it is used for
  2. What you need to know before taking Evrenzo
  3. How to take Evrenzo
  4. Possible side effects
  5. How to store Evrenzo
  6. Contents of the pack and other information

1. What Evrenzo is and what it is used for

What Evrenzo is
Evrenzo is a medicine that increases the number of red blood cells and the level of haemoglobin in the blood.
It contains the active substance roxadustat.
What Evrenzo is used for
Evrenzo is used to treat adults with symptomatic anaemia that develops in patients with chronic kidney disease. Anaemia is a condition characterised by an insufficient number of red blood cells and excessively low haemoglobin levels. As a result, the body may not receive enough oxygen. Anaemia can cause symptoms such as tiredness, weakness, or shortness of breath.
How Evrenzo works
Roxadustat works by increasing the level of hypoxia-inducible factor, a substance in the body that enhances red blood cell production when oxygen levels are low. By increasing the levels of this factor, the medicine boosts red blood cell and haemoglobin production (the protein that carries oxygen and is contained in red blood cells). This improves oxygen delivery to the body and may reduce the symptoms of anaemia.

2. What you should know before taking Evrenzo

Do not take Evrenzo

• if you are allergic to peanuts or soy.
• if you are allergic to roxadustat or to any of the other ingredients of this medicine (listed in section 6).
• if you are more than 6 months pregnant (it is also advisable to avoid this medicine during the first 6 months; see the section on pregnancy).
• if you are breastfeeding.

Warnings and precautions
Talk to your doctor or pharmacist before taking Evrenzo:

• if you have epilepsy or have previously had seizures or convulsive attacks
• if you show signs and symptoms of an infection, which may include fever, sweating or chills, sore throat, runny nose, shortness of breath, feeling weak, confusion, cough, vomiting, diarrhoea or stomach ache, burning sensation when urinating, red or painful skin, or sores on the body
• if you have a liver disease.

Chronic kidney disease and anaemia may increase the risk of cardiovascular events and death.
Managing anaemia is important. Your doctor will monitor your haemoglobin and will also consider your treatment regimen, as anaemia treatment and switching between different anaemia treatments may also negatively impact cardiovascular health.

Contact your doctor or pharmacist immediately:

• if you develop blood clots:
  1. in the leg veins (deep vein thrombosis, DVT), symptoms of which may include pain and/or swelling in the legs, cramps or a feeling of warmth in the affected leg;
  2. in the lungs (pulmonary embolism, PE), symptoms of which may include sudden shortness of breath, chest pain (typically worse when breathing), feeling anxious, dizziness, mild confusion or fainting, palpitations, cough (sometimes with blood);
  3. in the haemodialysis access (vascular access thrombosis, VAT), which prevent the vascular access from functioning; symptoms may include swelling, redness, hardening or thickening of the skin around the access site, discharge from the access site, or absence of vibration ("thrill") at the access site;
• if you have a seizure (convulsion or fit) or possible warning signs of a seizure, such as headache, irritability, fear, confusion, or unusual sensations;
• if you show signs and symptoms of an infection, including fever, sweating or chills, sore throat, runny nose, shortness of breath, feeling weak or faint, confusion, cough, vomiting, diarrhoea or stomach ache, burning sensation when urinating, red or painful skin, or sores on the body;
• if you show signs and symptoms of stroke (cerebrovascular accident), including sudden weakness or numbness of the face, arms, or legs, especially on one side of the body, sudden confusion, difficulty speaking or understanding speech, sudden vision problems in one or both eyes, severe headache, loss of consciousness or fainting, seizures (epileptic fits), loss of coordination, or loss of balance.

Inappropriate use may lead to an increase in blood cells and consequently thicken the blood. This may cause potentially fatal problems to the heart or blood vessels.

Children and adolescents
Do not give Evrenzo to children or adolescents under 18 years of age, as there is insufficient information on its use in this age group.

Other medicines and Evrenzo
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Evrenzo may affect the action of these medicines, or these medicines may affect the action of Evrenzo.

In particular, inform your doctor or pharmacist if you are taking or have taken any of the following medicines:

• medicines to reduce phosphate levels in the blood (called phosphate binders) or other medicines or supplements containing calcium, iron, magnesium, or aluminium (called multivalent cations), such as sevelamer carbonate or calcium acetate. You must take Evrenzo at least 1 hour after these medicines or supplements. Otherwise, roxadustat will not be properly absorbed by your body.
• a medicine used to treat gout, called probenecid.
• medicines used to lower cholesterol, such as simvastatin, atorvastatin, or rosuvastatin (also called "statins") or gemfibrozil.
• other medicines used to treat anaemia, such as erythropoiesis-stimulating agents (ESAs).

If you regularly take any of these medicines, your doctor may switch you to a different medicine to use during treatment with Evrenzo.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, talk to your doctor.
Evrenzo may have harmful effects on the foetus. Evrenzo is not recommended during the first 6 months of pregnancy and must not be taken during the last 3 months of pregnancy. Women of childbearing potential who are taking Evrenzo should use an effective method of contraception during treatment with Evrenzo and for at least one week after the last dose of Evrenzo. If you use a hormonal contraceptive, you should also use a barrier method, such as a condom or diaphragm.
Do not breastfeed while being treated with Evrenzo. It is not known whether Evrenzo passes into breast milk and could harm the baby.

Driving and using machines
This medicine may affect your ability to drive or operate machinery. Seizures may occur as a side effect (see section 4).

Evrenzo contains lactose, soy lecithin and Allura Red AC aluminium lake
Evrenzo contains sugar (lactose), traces of peanuts and soy (soy lecithin), and an azo dye (Allura Red AC aluminium lake). If your doctor has informed you of an intolerance to certain sugars or if you are allergic to peanuts, soy, or azo dyes, talk to your doctor before taking this medicine.

3. How to take Evrenzo

Take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.
Your doctor will tell you what dose of Evrenzo to take.
Your doctor will regularly monitor your haemoglobin levels and will increase or decrease the dose based on these levels.
Evrenzo is taken by mouth as tablets.

How to take Evrenzo

• Take your dose of Evrenzo three times a week unless otherwise instructed by your doctor.
• Never take Evrenzo on consecutive days.
• Take Evrenzo on the same three days each week.
• Evrenzo may be taken with food or between meals.
• Swallow the tablets whole.
• Do not chew, break, or crush the tablets.

Take Evrenzo at least 1 hour after taking medicines that reduce phosphate levels in the blood (called phosphate binders) or other medicines or supplements containing calcium, iron, magnesium, or aluminium (called multivalent cations).

Dosing schedule
Weekly dosing schedule, 3 times a week
Evrenzo is supplied in a blister pack containing 4 weeks' supply of medicine (12 tablets), divided into 4 rows. Each row contains 1 week of medicine (3 tablets). Make sure to take tablets from the same row each week.
The dose ranges from 20 mg three times a week up to a maximum of 400 mg three times a week.

Different dosing frequencies
In exceptional cases (based on haemoglobin levels), your doctor may decide to reduce the dose of Evrenzo to 20 mg twice weekly or once weekly. In such cases, your doctor will tell you on which days of the week you should take the dose.

Need for more than 1 tablet to achieve a dose
In most cases, you will receive 1 blister pack per month. If your dose requires more than 1 blister pack, you will need to take one tablet from each blister pack on each dosing day. Your doctor will explain when and how many tablets to take.

Your doctor will monitor your haemoglobin levels and may temporarily stop treatment if your haemoglobin level becomes too high. Do not restart treatment until your doctor tells you to do so. Your doctor will tell you what dose of Evrenzo to take and when to restart treatment.

If you take more Evrenzo than you should
If you take more tablets or a higher dose than you should, contact your doctor immediately.

If you forget to take Evrenzo

• Never take a double dose to make up for a forgotten dose.
• If more than 24 hours (1 day) remain before your next scheduled dose, take the missed dose as soon as possible, then take your next dose on the next scheduled day.
• If less than 24 hours (1 day) remain before your next scheduled dose, do not take the missed dose; take your next dose on the next scheduled day.

If you stop taking Evrenzo
Do not stop taking this medicine unless your doctor tells you to do so.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some possible side effects could be serious. Immediately contact your doctor if you experience any of the following:

• Blood clot in the leg veins (deep vein thrombosis, DVT) (common – may occur in up to 1 in 10 people).
• Blood clot in the lungs (pulmonary embolism) (uncommon – may occur in up to 1 in 100 people).
• Blood clot in the dialysis access (vascular access thrombosis, VAT), causing closure or interruption of function of the vascular access if you are using a
  fistula or graft for dialysis access (very common – may occur in more than 1 in 10 people).
• Stroke (cerebrovascular accident) (uncommon – may occur in up to 1 in 100 people).
• Low platelet count in the blood (thrombocytopenia) (common – may occur in up to 1 in 10 people), which may present as unexplained bruising or a skin rash with small red spots (called petechiae), prolonged bleeding from skin cuts, bleeding from gums or nose, blood in urine or stools, or bleeding in the whites of the eyes.
• Seizures and warning signs of seizures (seizures or fits) (common – may occur in up to 1 in 10 people).
• Sepsis, a serious infection or, in rare cases, life-threatening (common – may occur in up to 1 in 10 people).
• Redness and peeling of the skin over a large area of the body, which may be itchy or painful (exfoliative dermatitis) (frequency cannot be determined from available data).

Other possible side effects
Very common (may occur in more than 1 in 10 people):

• Increased potassium levels
• High blood pressure (hypertension)
• Nausea
• Diarrhoea
• Swelling due to fluid retention in limbs (peripheral oedema)

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

• Difficulty sleeping (insomnia)
• Headache
• Vomiting
• Constipation
• Low platelet count in the blood (thrombocytopenia)

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

• Increased bilirubin levels in the blood

Not known (frequency cannot be determined from available data):

• Decreased thyroid function
• Increased blood copper levels

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Evrenzo

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 blister after
Exp./EXP. The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Evrenzo contains
Evrenzo 20 mg:

• The active substance is roxadustat. Each film-coated tablet contains 20 mg of roxadustat.

Evrenzo 50 mg:

• The active substance is roxadustat. Each film-coated tablet contains 50 mg of roxadustat.

Evrenzo 70 mg:

• The active substance is roxadustat. Each film-coated tablet contains 70 mg of roxadustat.

Evrenzo 100 mg:

• The active substance is roxadustat. Each film-coated tablet contains 100 mg of roxadustat.

Evrenzo 150 mg:

• The active substance is roxadustat. Each film-coated tablet contains 150 mg of roxadustat.
  The other components are:
• tablet core: lactose monohydrate, microcrystalline cellulose (E460), croscarmellose sodium (E468), povidone (E1201), magnesium stearate (E470b).
• film coating: polyvinyl alcohol (E1203), talc (E553b), macrogol (E1521), aluminium lake of red allura AC (E129), titanium dioxide (E171), lecithin (soy) (E322).

See section 2 “Evrenzo contains lactose, soy lecithin and aluminium lake of red allura AC”.
Description of the appearance of Evrenzo and contents of the pack
Evrenzo 20 mg tablets are red, oval, film-coated tablets, with “20” engraved on one side.
Evrenzo 50 mg tablets are red, oval, film-coated tablets, with “50” engraved on one side.
Evrenzo 70 mg tablets are red, round, film-coated tablets, with “70” engraved on one side.
Evrenzo 100 mg tablets are red, oval, film-coated tablets, with “100” engraved on one side.
Evrenzo 150 mg tablets are red, almond-shaped, film-coated tablets, with “150” engraved on one side.
Evrenzo is available in unit-dose divisible blisters made of PVC/aluminium, in packs containing 12 x 1 film-coated tablets (tablets) and 36 x 1 film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorization Holder
Astellas Pharma Europe B.V.
Sylviusweg 62
2333 BE Leiden
The Netherlands
Manufacturer
Delpharm Meppel B.V.
Hogemaat 2
7942 JG Meppel
The Netherlands
For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:
België/Belgique/Belgien Lietuva
Astellas Pharma B.V. Branch Astellas Pharma d.o.o.
Tél/Tel: +32 (0)2 5580710 Tel.: +370 37 408 681
България
Астелас Фарма ЕООД
Teл.: +359 2 862 53 72
Luxembourg/Luxemburg
Astellas Pharma B.V. Branch
Belgique/Belgien
Tél/Tel: +32 (0)2 5580710
Česká republika Magyarország
Astellas Pharma s.r.o. Astellas Pharma Kft.
Tel: +420 221 401 500 Tel.: +36 1 577 8200
Danmark Malta
Astellas Pharma a/s Astellas Pharmaceuticals AEBE
Tlf.: +45 43 430355 Tel: +30 210 8189900
Deutschland Nederland
Astellas Pharma GmbH Astellas Pharma B.V.
Tel.: +49 (0)89 454401 Tel: +31 (0)71 5455745
Eesti Norge
Astellas Pharma d.o.o. Astellas Pharma
Tel: +372 6 056 014 Tlf: +47 66 76 46 00
Ελλάδα Österreich
Astellas Pharmaceuticals AEBE Astellas Pharma Ges.m.b.H.
Τηλ: +30 210 8189900 Tel.: +43 (0)1 8772668
España Polska
Astellas Pharma S.A. Astellas Pharma Sp.z.o.o.
Tel: +34 91 4952700 Tel.: +48 225451 111
France Portugal
Astellas Pharma S.A.S. Astellas Farma, Lda.
Tél: +33 (0)1 55917500 Tel: +351 21 4401300
Hrvatska România
Astellas d.o.o. S.C. Astellas Pharma SRL
Tel: +385 1670 0102 Tel: +40 (0)21 361 04 95
Ireland Slovenija
Astellas Pharma Co. Ltd. Astellas Pharma d.o.o.
Tel: +353 (0)1 4671555 Tel: +386 14011400
Ísland Slovenská republika
Vistor Astellas Pharma s.r.o.
Sími: +354 535 7000 Tel: +421 2 4444 2157
Italia Suomi/Finland
Astellas Pharma S.p.A. Astellas Pharma
Tel: +39 (0)2 921381 Puh/Tel: +358 (0)9 85606000
Κύπρος Sverige
Ελλάδα Astellas Pharma AB
Astellas Pharmaceuticals AEBE Tel: +46 (0)40-650 15 00
Τηλ: +30 210 8189900
Latvija
Astellas Pharma d.o.o.
Tel: +371 67 619365
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.