EVRENZO 20 mg Film-Coated Tablets

Содержание инструкции

1. 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
   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. How to store Evrenzo
   6. Package contents and other information

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

Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you start to take 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 pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell 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 you take 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 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.
It contains the active substance roxadustat.

What is Evrenzo 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 an excessively low level of haemoglobin. As a result, the body may not
receive enough oxygen. Anaemia can cause symptoms such as fatigue,
weakness or shortness of breath.

How Evrenzo works
Roxadustat, the active substance of Evrenzo, works by increasing the level of hypoxia-inducible factor, a substance present in the body that increases the production of red blood cells when
oxygen levels are low. By increasing the levels of this factor, the medicine increases the
production of red blood cells and haemoglobin levels (the protein that carries oxygen, contained in
red blood cells). This increases the oxygen supply to 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 peanuts or soy, do not use this medicine. Evrenzo contains soy lecithin
• if you are allergic to roxadustat or 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 at the beginning of pregnancy - see the section on pregnancy)
• if you are breastfeeding.

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

• if you suffer from epilepsy or if you have had seizures or convulsive attacks in the past
• 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 pain, burning sensation when urinating, red or sore skin or sores on the body
• if you suffer from a liver disease.

Chronic kidney disease and anaemia can increase the risk of cardiovascular events and death.
Managing anaemia is important. Your doctor will monitor your haemoglobin and will also take into account your
treatment regimen because treatment for anaemia and switching between different anaemia treatments may also have a negative impact on cardiovascular health.
Contact your doctor or pharmacist immediately:

• if you develop blood clots:
• 1. in the veins of the legs (deep vein thrombosis, DVT), whose symptoms 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), whose symptoms may include sudden shortness of breath, chest pain (usually worse when breathing), feeling anxious, dizziness, lightheadedness or fainting, palpitations, cough (sometimes with blood);
• 3. in the access of haemodialysis (vascular access thrombosis, VAT) which prevents the vascular access from working; symptoms may include swelling, redness, hardening or thickening of the skin around the access, leakage at the access site, loss of sensation of vibration (“thrill”) in the access area;
• if you have a convulsive crisis (seizure or attack) or possible warning signs of a convulsive crisis, such as headache, irritability, fear, confusion or unusual sensations;
• if you show signs and symptoms of an infection, which include fever, sweating or chills, sore throat, runny nose, shortness of breath, feeling weak or fainting, confusion, cough, vomiting, diarrhoea or stomach pain, burning sensation when urinating, red or sore skin or sores on the body.
• if you show signs and symptoms of a stroke (cerebrovascular accident), which include sudden weakness or numbness of the face, arms or legs, especially on one side of the body, sudden confusion, difficulty speaking or understanding, sudden difficulty in vision in one or both eyes, severe headache, loss of consciousness or fainting, seizures (fits), loss of coordination, loss of balance.

Inappropriate use may lead to an increase in blood cells and consequently
thicken the blood. This can cause potentially life-threatening problems with the heart or blood vessels.

Children and adolescents
Do not give Evrenzo to children and adolescents under 18 years of age because there is not enough
information available about 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 can affect the action of these medicines or these
medicines can affect the action of Evrenzo.
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 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 absorbed correctly by the body
• a medicine 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.

If you normally take any of these medicines, your doctor may change them and prescribe
a different medicine to use during treatment with Evrenzo.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, talk to your doctor.
Evrenzo may have harmful effects on the foetus. Evrenzo is not recommended in the first 6 months of
pregnancy and must not be taken in the last 3 months of pregnancy. Women who are able to become
pregnant while taking Evrenzo must use effective contraception during
treatment with Evrenzo and for at least one week after the last dose of Evrenzo. If you use
hormonal contraception, you should also use a barrier method, such as a condom or diaphragm.
Do not breastfeed while you are 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 can impair your ability to drive or operate machinery. As a side
effect, seizures (fits) may occur (see section 4).

Evrenzo contains lactose, soy lecithin and aluminium lake red allura AC
Evrenzo contains sugar (lactose), traces of peanuts and soy (soy lecithin) and an azo dye
(aluminium lake red allura AC). If you have been told by your doctor that you have an intolerance to some
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 following exactly the instructions of your doctor or pharmacist. If you
have any doubts, ask your doctor or pharmacist.
Your doctor will tell you which dose of Evrenzo to take.
Your doctor will regularly check your haemoglobin levels and will increase or decrease the dose based on those
levels.
Evrenzo is taken by mouth in the form of tablets.

How to take Evrenzo

• Take the dose of Evrenzo three times a week unless otherwise indicated by your doctor
• Never take Evrenzo on consecutive days
• Take Evrenzo on the same three days each week
• Evrenzo can 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 lower phosphate levels in the blood
(called phosphate binders) or other medicines or supplements containing calcium, iron, magnesium or
aluminium (called multivalent cations).

Dosing schedule

Dosing schedule 3 times a week
Evrenzo is supplied in a blister pack containing medicine for 4 weeks (12 tablets), divided into 4 rows.
Each row contains 1 week of medicine (3 tablets). Make sure to take the tablets from the
same row for each week.
The dose is between 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 or once a week. In this case, your doctor will tell you on which days of the
week you should take the dose.

Need for more than 1 tablet to compensate for a dose
In most cases, you will have 1 blister pack per month. If the dose requires more than 1 blister pack, you will
need to take one tablet from each blister pack per day of administration. Your doctor will explain when
and how many tablets to take.
Your doctor will monitor your haemoglobin level and may temporarily suspend treatment
if your haemoglobin level becomes too high. Do not start treatment again until
your doctor tells you to. Your doctor will tell you which 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 or a higher dose than you should, seek immediate medical attention.

If you forget to take Evrenzo

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

If you stop taking Evrenzo
Do not stop taking this medicine unless your doctor has told you to do so.
If you have any doubts about 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 everyone will experience them.

Some possible side effects may be serious. Seek immediate medical attention
if you experience any of the following effects:

• blood clot in the veins of the legs (deep vein thrombosis, 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 hemodialysis access (vascular access thrombosis, VAT) causing closure of the vascular access or interruption of its function if you are using a fistula or graft for dialysis access (may affect more than 1 in 10 people)
• stroke (cerebrovascular accident) (may affect up to 1 in 100 people)
• low levels of platelets in the blood (thrombocytopenia) (may affect up to 1 in 10 people) which may appear as unexplained bruising or as a rash with small red spots (called petechiae), prolonged bleeding from skin cuts, bleeding from the gums or nose, blood in the urine or stool, bleeding in the whites of the eyes
• seizures and warning signs of seizures (convulsions or fits) (may affect up to 1 in 10 people)
• sepsis, a serious infection or, in rare cases, life-threatening (may affect 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 estimated based on available data).

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

• increased amount of potassium
• high blood pressure (hypertension)
• nausea
• diarrhea
• swelling due to fluid retention in the limbs (peripheral edema)

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

• difficulty sleeping (insomnia)
• headache
• vomiting
• constipation
• low levels of platelets in the blood (thrombocytopenia).

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

• increased amount of bilirubin in the blood

Not known (frequency cannot be estimated based on available data):

• decreased thyroid function
• increased blood copper

Reporting of side effects
If you get 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 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 which is stated on the box and blister after
Expiry Date/EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine in 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 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:

• tablet core: lactose monohydrate, microcrystalline cellulose (E460), sodium croscarmellose (E468), povidone (E1201), magnesium stearate (E470b)
• film coating: polyvinyl alcohol (E1203), talc (E553b), macrogol (E1521), allura red AC aluminium lake (E129), titanium dioxide (E171), lecithin (soy) (E322)

Description of Evrenzo and package contents
Evrenzo 20 mg tablets are oval, red film-coated tablets, with “20” inscribed
on one side.
Evrenzo 50 mg tablets are oval, red film-coated tablets, with “50” inscribed
on one side.
Evrenzo 70 mg tablets are round, red film-coated tablets, with “70” inscribed
on one side.
Evrenzo 100 mg tablets are oval, red film-coated tablets, with “100” inscribed
on one side.
Evrenzo 150 mg tablets are almond-shaped, red film-coated tablets, with “150” inscribed
on one side.
Evrenzo is available in blister packs with divisible unit doses in PVC/aluminium, in packs of 12 x 1
film-coated tablets and 36 x 1 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation 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 medicine, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Astellas Pharma B.V. Branch
Tél/Tel: +32 (0)2 5580710

Lietuva
Astellas Pharma d.o.o.
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
Astellas Pharma s.r.o.
Tel: +420 221 401 500

Magyarország
Astellas Pharma Kft.
Tel.: +36 1 577 8200

Danmark
Astellas Pharma a/s
Tlf: +45 43 430355

Malta
Astellas Pharmaceuticals AEBE
Tel: +30 210 8189900

Deutschland
Astellas Pharma GmbH
Tel.: +49 (0)89 454401

Nederland
Astellas Pharma B.V.
Tel: +31 (0)71 5455745

Eesti
Astellas Pharma d.o.o.
Tel: +372 6 056 014

Norge
Astellas Pharma
Tlf: +47 66 76 46 00

Ελλάδα
Astellas Pharmaceuticals AEBE
Τηλ: +30 210 8189900

Österreich
Astellas Pharma Ges.m.b.H.
Tel.: +43 (0)1 8772668

España
Astellas Pharma S.A.
Tel: +34 91 4952700

Polska
Astellas Pharma Sp.z.o.o.
Tel.: +48 225451 111

France
Astellas Pharma S.A.S.
Tél: +33 (0)1 55917500

Portugal
Astellas Farma, Lda.
Tel: +351 21 4401300

Hrvatska
Astellas d.o.o.
Tel: +385 1670 0102

România
S.C. Astellas Pharma SRL
Tel: +40 (0)21 361 04 95

Ireland
Astellas Pharma Co. Ltd.
Tel: +353 (0)1 4671555

Slovenija
Astellas Pharma d.o.o.
Tel: +386 14011400

Ísland
Vistor hf
Sími: +354 535 7000

Slovenská republika
Astellas Pharma s.r.o.
Tel: +421 2 4444 2157

Italia
Astellas Pharma S.p.A.
Tel: +39 (0)2 921381

Suomi/Finland
Astellas Pharma
Puh/Tel: +358 (0)9 85606000

Κύπρος
Ελλάδα
Astellas Pharmaceuticals AEBE
Τηλ: +30 210 8189900

Sverige
Astellas Pharma AB
Tel: +46 (0)40-650 15 00

United Kingdom(Northern Ireland)
Astellas Pharma Co., Limited
Tel: +353 (0)1 4671555
Free call from Northern Ireland: 0800 783 5018

Other sources of information
More detailed information on this medicine is available on the European Medicines Agency website, https://www.ema.europa.eu.

Latvija
Astellas Pharma d.o.o.
Tel: +371 67 619365

APPENDIX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR VARIATION OF THE(S) MARKETING AUTHORISATION(S)
Scientific conclusions
Considering the evaluation by the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Report (PSUR) for roxadustat, the PRAC’s scientific conclusions are as follows:
In light of the available data on ischemic cerebrovascular events from clinical studies, the literature, spontaneous reports including in some cases a close temporal association, a de-challenge and a positive re-challenge and in light of a plausible mechanism of action, the PRAC considers that a causal relationship between roxadustat and stroke is at least a reasonable possibility. The PRAC concluded that the product information for roxadustat-containing medicinal products should be amended accordingly. Furthermore, based on concerns raised by the marketing authorisation holder, relating to the fact that the symptoms listed in section 4 may affect up to 1 in 10 people, the PRAC concluded that the product information for roxadustat-containing medicinal products should be amended to avoid this misinterpretation.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products
(CHMP) agrees with the overall conclusions and with the justification of the recommendation.

Justification for variation of the marketing authorisation(s)
Based on the scientific conclusions on roxadustat, the CHMP considers that the benefit/risk balance of the medicinal product(s) containing roxadustat remains unchanged subject to the proposed changes to the product information.
The CHMP recommends the variation of the marketing authorisation(s).