EVRENZO 20 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Evrenzo20mg film-coated tablets

Evrenzo50mg film-coated tablets

Evrenzo70mg film-coated tablets

Evrenzo100mg film-coated tablets

Evrenzo150mg film-coated tablets

roxadustat

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start 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, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Evrenzo and what is it used for

What is Evrenzo

Evrenzo is a medicine that increases the number of red blood cells and the level of haemoglobin in the blood. The active substance it contains is roxadustat.

What Evrenzo is used for

Evrenzo is used to treat symptomatic anaemia that occurs in adult patients with chronic kidney disease. Anaemia occurs when you have too few red blood cells and your haemoglobin level is too low. As a result, your body may not get enough oxygen. Anaemia can cause symptoms such as tiredness, weakness or shortness of breath.

How Evrenzo works

Roxadustat, the active substance in Evrenzo, increases the level of HIF, a substance in the body that increases the production of red blood cells when oxygen levels are low. By increasing the level of HIF, this medicine increases the production of red blood cells and haemoglobin levels (the protein that carries oxygen in red blood cells). This improves the supply of oxygen to all parts of the body and may reduce the symptoms of anaemia.

2. What you need to know before you take Evrenzo

Do not take Evrenzo

• If you are allergic to peanut or soya, do not use this medicine. Evrenzo contains soya lecithin.
• If you are allergic to roxadustat or any of the other ingredients of this medicine (listed in section 6).
• If you are pregnant for more than 6 months, (it is also better to avoid this medicine in the early stages of pregnancy; see the section on pregnancy).
• If you are breast-feeding.

Warnings and precautions

Talk to your doctor or pharmacist before starting Evrenzo:

• If you have epilepsy or have ever had seizures or fits.
• If you have signs or symptoms of an infection, such as fever, sweats or chills, sore throat, runny nose, shortness of breath, feeling weak or faint, confusion, cough, vomiting, diarrhoea or stomach pain, burning sensation when urinating, redness or pain of the skin or body sores.
• If you have a liver disorder.

Chronic kidney disease and anaemia may increase the risk of cardiovascular events and death. It is important to treat your anaemia. Your doctor will monitor your haemoglobin and determine your treatment schedule, as treatment for anaemia and switching between anaemia treatments may also have a negative impact on your cardiovascular health.

Talk to your doctor or pharmacist immediately:

• If you get blood clots:

1. In the veins of the legs (deep vein thrombosis or DVT), whose signs may include pain or swelling of the legs and cramps or a feeling of warmth in the affected leg.
2. In the lungs (pulmonary embolism or PE), whose signs may include sudden shortness of breath, chest pain (usually worse when breathing), feeling anxious, dizzy, faint or passing out, fast heart rate or cough (sometimes with blood).
3. In your access for haemodialysis (vascular access thrombosis or VAT) that stops the vascular access from working; the signs of this may include swelling, redness, hardening or thickening of the skin around the access, oozing from the access site or absence of the feeling of vibration ("thrill") over the access area.

• If you experience a seizure or possible warning signs of a seizure, such as headache, irritability, fear, confusion or unusual sensations.
• If you have signs or symptoms of an infection, such as fever, sweats or chills, sore throat, runny nose, shortness of breath, feeling weak or faint, confusion, cough, vomiting, diarrhoea or stomach pain, burning sensation when urinating, redness or pain of the skin or body sores.
• If you have signs and symptoms of a stroke (cerebrovascular accident), which include sudden weakness or numbness of the face, arm or leg, especially on one side of the body, sudden confusion, trouble speaking or understanding, sudden trouble seeing with one or both eyes, severe headache, loss of consciousness or fainting, seizure (fits), loss of coordination, loss of balance.

Misuse of the medicine can cause an increase in blood cells and, as a consequence, thicken the blood. This can cause potentially life-threatening problems related to the heart or blood vessels.

Children and adolescents

Do not give Evrenzo to children and adolescents under 18 years of age as there is not enough information available 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 way these medicines work or these medicines may affect the way Evrenzo works.

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

• Medicines to reduce phosphate levels in the blood (called phosphate binders) or other medicines or supplements that contain calcium, iron, magnesium or aluminium (called multivalent cations), such as sevelamer carbonate or calcium acetate. You should take Evrenzo at least 1 hour after taking these medicines or supplements. Otherwise, your body may not absorb roxadustat properly.
• A medicine for the treatment of 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 normally take any of these medicines, your doctor may change your treatment and prescribe another one that you should take during the time you are taking Evrenzo.

Pregnancy, breast-feeding and fertility

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor.

Evrenzo may harm your baby. Evrenzo is not recommended during the first 6 months of pregnancy and should not be taken during the last 3 months of pregnancy. Women who take Evrenzo and may become pregnant should use an effective contraceptive method during treatment with Evrenzo and for at least one week after the last dose of Evrenzo. If you use a hormonal contraceptive method, you should also use a barrier method, such as a condom or diaphragm.

If you are being treated with Evrenzo, do not breast-feed your child. It is not known if Evrenzo passes into breast milk; if it does, it could harm your baby.

Driving and using machines

This medicine may affect your ability to drive or use machines. You may experience a seizure; it is one of the possible side effects (see section 4).

Evrenzo contains lactose, soya lecithin and red iron oxide Allura AC lacquer

Evrenzo contains sugar (lactose), traces of peanut and soya (soya lecithin) and an azo colouring (red iron oxide Allura AC lacquer). If your doctor has told you that you have an intolerance to some sugars or that you are allergic to peanut, soya or azo colourings, consult your doctor before taking this medicine.

3. How to take Evrenzo

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

Your doctor will tell you the dose of Evrenzo to take.

Additionally, your doctor will measure your haemoglobin levels periodically and, if necessary, increase or decrease your dose.

Evrenzo is taken orally in the form of tablets.

Taking Evrenzo

• Take your dose of Evrenzo three times a week, unless your doctor has told you otherwise.
• Never take Evrenzo on consecutive days.
• Take Evrenzo on the same three days of each week.
• Evrenzo can be taken with or without food.
• Swallow the tablets whole.
• Do not chew, crush or break the tablets.

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

Dosing schedule

Three times a week dosing schedule

Evrenzo is presented in a blister pack that contains medicine for 4 weeks (12 tablets) divided into 4 rows. Each row contains the medicine for 1 week (3 tablets). Make sure to take the tablets from the same row each week.

Your dose may range from 20 mg three times a week to a maximum of 400 mg three times a week.

Different dosing frequencies

In exceptional cases (depending on your haemoglobin levels), your doctor may decide to reduce your dose of Evrenzo to 20 mg twice or once a week. In this case, your doctor will tell you which day or days of the week you should take the dose.

If the dose requires more than1tablet

In most cases, you will have 1 blister pack per month. If your dose requires more than 1 blister pack, you should take 1 tablet from each blister pack on each day you have a scheduled dose. Your doctor will tell you how many tablets to take and when to take them.

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

If you take more Evrenzo than you should

If you take more tablets than you should 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 forgotten doses.
• If it is more than 24 hours (1 day) before your next scheduled dose, take the missed dose as soon as possible and your next dose on the day it is scheduled.
• If it is less than 24 hours (1 day) before your next scheduled dose: skip the missed dose and take your next dose on the day it is scheduled.

If you stop taking Evrenzo

Do not stop taking this medicine unless your doctor has told you to.

If you have any further questions on the use of this medicine, ask 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 may be serious. Contact your doctor immediately if you experience any of the following:

• Blood clot in the veins of the legs (deep vein thrombosis or DVT) (may affect up to 1 in 10 people).
• Blood clot in the lungs (pulmonary embolism) (may affect up to 1 in 100 people).
• Blood clot in the access for haemodialysis (vascular access thrombosis or VAT) that causes the vascular access to become blocked or stop working if you are using a fistula or graft for access for dialysis (may affect more than 1 in 10 people).
• Unexplained bruising or rash of small red spots on the skin (called petechiae), prolonged bleeding from cuts in the skin, bleeding from the gums or nose, blood in the urine or stools, bleeding in the white of the eyes (low platelet count in the blood, thrombocytopenia) (may affect 1 in 10 people).
• Seizures and warning signs of seizures (convulsions or fits) (may affect up to 1 in 10 people).
• Sepsis, a severe and potentially life-threatening infection (may affect up to 1 in 10 people).
• Redness and peeling of the skin over a large area of the body, which may cause itching or pain (exfoliative dermatitis) (frequency cannot be estimated from the available data).

Other possible side effects

Very common (may affect more than1in10people)

• Increased potassium level
• High blood pressure (hypertension)
• Feeling sick (nausea)
• Diarrhoea
• Swelling due to fluid retention in the limbs (peripheral oedema)

Common (may affect up to1in10people)

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

Uncommon (may affect up to1in100people)

• Increased bilirubin level in the blood

Frequency not known (cannot be estimated from the available data)

• Decreased thyroid function
• Increased copper level in the blood

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Evrenzo

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the blister after EXP. The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Package Contents and Additional Information

Composition of Evrenzo

Evrenzo 20 mg:

• The active ingredient is roxadustat. Each tablet contains 20 mg of roxadustat.

Evrenzo 50 mg:

• The active ingredient is roxadustat. Each tablet contains 50 mg of roxadustat.

Evrenzo 70 mg:

• The active ingredient is roxadustat. Each tablet contains 70 mg of roxadustat.

Evrenzo 100 mg:

• The active ingredient is roxadustat. Each tablet contains 100 mg of roxadustat.

Evrenzo 150 mg:

• The active ingredient is roxadustat. Each tablet contains 150 mg of roxadustat.

The other ingredients are:

• Core of the tablet: lactose monohydrate, microcrystalline cellulose (E460), sodium croscarmellose (E468), povidone (E1201), magnesium stearate (E470b).

• Coating: polyvinyl alcohol (E1203), talc (E553b), macrogol (E1521), red aluminum lake Allura AC (E129), titanium dioxide (E171), soy lecithin (E322).

Appearance of the Product and Package Contents

Evrenzo 20 mg are film-coated, oval tablets, red in color and with the number "20" in low relief on one of their faces.

Evrenzo 50 mg are film-coated, oval tablets, red in color and with the number "50" in low relief on one of their faces.

Evrenzo 70 mg are film-coated, round tablets, red in color and with the number "70" in low relief on one of their faces.

Evrenzo 100 mg are film-coated, oval tablets, red in color and with the number "100" in low relief on one of their faces.

Evrenzo 150 mg are film-coated, almond-shaped tablets, red in color and with the number "150" in low relief on one of their faces.

Evrenzo is available in packages containing 12 × 1 film-coated tablets and 36 × 1 film-coated tablets in PVC/aluminum blisters with pre-cut doses.

Only some package sizes may be marketed.

Marketing Authorization Holder

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

Netherlands

Manufacturer

Delpharm Meppel B.V.

Hogemaat 2

7942 JG Meppel

Netherlands

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:MM/AAAA

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.