Krystexxa

Informazzjoni prinċipali

  • Isem kummerċjali:
  • Krystexxa
  • Dominju tal-mediċina:
  • Bnedmin
  • Tip ta 'mediċina:
  • Droga allopatika

Dokumenti

Lokalizzazzjoni

  • Disponibbli fi:
  • Krystexxa
    Unjoni Ewropea
  • Lingwa:
  • Ingliż

Informazzjoni terapewtika

  • Grupp terapewtiku:
  • ANTIGOUT PREPARATIONS
  • Żona terapewtika:
  • Gout
  • Indikazzjonijiet terapewtiċi:
  • Krystexxa is indicated for the treatment of severe debilitating chronic tophaceous gout in adult patients who may also have erosive joint involvement and who have failed to normalize serum uric acid with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these medicines are contraindicated.
  • Sommarju tal-prodott:
  • Revision: 3

Status

  • Sors:
  • EMA - European Medicines Agency
  • L-istatus ta 'awtorizzazzjoni:
  • Withdrawn
  • Numru ta 'awtorizzazzjoni:
  • EMEA/H/C/002208
  • Data ta 'l-awtorizzazzjoni:
  • 07-01-2013
  • Kodiċi EMEA:
  • EMEA/H/C/002208
  • L-aħħar aġġornament:
  • 31-03-2019

Rapport ta 'Valutazzjoni Pubblika

7 Westferry Circus

Canary Wharf

London E14 4HB

United Kingdom

Telephone

+44 (0)20 7418 8400

Facsimile

+44 (0)20 7418 8416

E-mail

info@ema.europa.eu

Website

www.ema.europa.eu

An agency of the European Union

© European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged.

EMA/684724/2012

EMEA/H/C/002208

EPAR summary for the public

Krystexxa

pegloticase

This is a summary of the European public assessment report (EPAR) for Krystexxa. It explains how the

Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in

favour of granting a marketing authorisation and its recommendations on the conditions of use for

Krystexxa.

What is Krystexxa?

Krystexxa is a medicine containing the active substance pegloticase. It is available as a concentrate

that is made up into a solution for infusion (drip) into a vein.

What is Krystexxa used for?

Krystexxa is used to treat adult patients with severe chronic (long-term) tophaceous gout. This is

where high levels of the substance uric acid develop in the blood and then crystallise in joints and

tissues, forming tophi (stones) that cause pain and joint damage. Krystexxa is only used in patients

who cannot control their uric acid levels even at maximum doses of conventional medicines called

xanthine oxidase inhibitors, or who are unable to use such medicines.

The medicine can only be obtained with a prescription.

How is Krystexxa used?

Treatment with Krystexxa should be given under the supervision of a doctor who has experience in the

treatment of severe chronic gout, in a setting where facilities for resuscitation are available.

Krystexxa is given as an infusion into a vein every two weeks, at a recommended dose of 8 mg. The

infusion is given slowly over at least 2 hours. All patients are monitored for any reactions during the

infusion and for at least one hour afterwards. To reduce the risk of these reactions, patients are given

other medicines before treatment with Krystexxa.

Medicinal product no longer authorised

Reactions are more common in patients who develop antibodies (proteins produced by the immune

system, the body’s natural defences) that reduce the effect of the treatment. Levels of uric acid are

therefore measured before each infusion and the doctor should only continue Krystexxa treatment as

long as the patient continues to benefit with uric acid levels in the blood lowered below a threshold of 6

mg/dl. Patients should not take other medicines that lower uric acid levels during Krystexxa treatment,

so that the effect of Krystexxa can be clearly judged.

For further information on the use of Krystexxa see the package leaflet.

How does Krystexxa work?

The active substance in Krystexxa, pegloticase, contains an enzyme called uricase. Uricase breaks

down uric acid into another substance, allantoin, which can be passed out of the body in the urine. This

lowers the levels of uric acid in the blood. Once levels of uric acid are below 6 mg/dl, this allows

crystals in the joints to dissolve, slowly shrinking the tophi.

The uricase in Krystexxa is produced by a method known as ‘recombinant DNA technology’: it is made

by a bacterium that has received a gene (DNA), which makes it able to produce uricase. In Krystexxa,

uricase has been attached to a chemical, polyethylene glycol (PEG), which decreases the rate at which

uricase is removed from the body, allowing its action to last longer.

How has Krystexxa been studied?

The effects of Krystexxa were first tested in experimental models before being studied in humans.

Krystexxa was studied in two main studies involving 225 patients with severe tophaceous gout in

whom allopurinol, a xanthine oxidase inhibitor, had previously failed to control their uric acid levels or

could not be used due to side effects. Krystexxa, given at a dose of 8 mg every two or four weeks, was

compared with placebo (a dummy treatment), over a period of six months. The main measure of

effectiveness was the number of patients who showed a persistent response to the treatment, defined

as uric acid level in the blood below 6 mg/dl for at least 80% of the time during both the third and

sixth months of the study.

What benefit has Krystexxa shown during the studies?

Krystexxa was shown to be more effective than placebo in reducing uric acid levels. Although uric acid

levels were quickly lowered by Krystexxa, its effect was reduced within a few weeks in more than half

the patients. Overall, 42% of patients (36 out of 85) given the medicine every two weeks showed a

persistent response; the figure for those given Krystexxa every four weeks was 35% (29 out of 84).

Placebo was not effective in any of the patients. Krystexxa given every two weeks resulted in fewer

reactions to the infusion than when it was given every four weeks.

What is the risk associated with Krystexxa?

The most common serious side effects with Krystexxa are anaphylaxis (a severe allergic reaction),

seen in about 7 patients in 100, infusion reactions (including flushing, skin rashes, itching, sweating,

chest pain, difficulty in breathing, chills, and raised blood pressure), seen in about 26 patients in 100,

and gout flares (worsening of gout symptoms) which were more common in the first 3 months of

treatment.

For the full list of side effects reported with Krystexxa, see the package leaflet.

Krystexxa

EMA/684724/2012

Page 2/3

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Krystexxa

EMA/684724/2012

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Krystexxa must not be used in people who are hypersensitive (allergic) to pegloticase or any of the

other ingredients, and in people with a rare blood disorder called glucose 6-phosphate dehydrogenase

(G6PD) deficiency (favism) or similar disorders.

Why has Krystexxa been approved?

The CHMP concluded that Krystexxa was highly effective in reducing uric acid levels. Although there

may be serious side effects (such as infusion reactions and gout flares) these were considered

manageable. For severely affected patients who cannot be treated effectively with conventional

methods, the Committee considered that Krystexxa addressed an unmet need, since no alternative

treatments are available. The CHMP therefore decided that Krystexxa’s benefits are greater than its

risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe use of Krystexxa?

The company that makes Krystexxa will carry out a study of the long-term safety of the medicine,

including its safety and effectiveness in patients who stop treatment and later restart it.

Other information about Krystexxa

The European Commission granted a marketing authorisation valid throughout the European Union for

Krystexxa on 8 January 2013.

The full EPAR for Krystexxa can be found on the Agency’s website: ema.europa.eu/Find

medicine/Human medicines/European public assessment reports. For more information about

treatment with Krystexxa, read the package leaflet (also part of the EPAR) or contact your doctor or

pharmacist.

This summary was last updated in 01-2013.

Medicinal product no longer authorised

Fuljett ta 'Informazzjoni għall-Pazjent: prodott - kompożizzjoni, indikazzjonijiet, effetti sekondarji, dożaġġ, interazzjonijiet, reazzjonijiet avversi, tqala, treddigħ

B. PACKAGE LEAFLET

Medicinal product no longer authorised

Package Leaflet: Information for the user

KRYSTEXXA 8 mg concentrate for solution for infusion

pegloticase

Read all of this leaflet carefully before you start using 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, pharmacist or nurse.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet.

What is in this leaflet

What KRYSTEXXA is and what it is used for

What you need to know before you receive KRYSTEXXA

How to use KRYSTEXXA

Possible side effects

How to store KRYSTEXXA

Contents of the pack and other information

1.

What KRYSTEXXA is and what it is used for

KRYSTEXXA contains the active substance pegloticase. Pegloticase belongs to the class anti-gout

medicines.

Pegloticase is used to treat severe long-term gout in adult patients who also have one or more painful

deposits of uric acid crystals under the skin that cause difficulty in carrying out daily activities and

who do not respond or cannot take other anti-gout medicines.

How KRYSTEXXA works

People with gout have too much uric acid in their body. Uric acid deposits as crystals in joints,

kidneys, and other organs which may cause profound pain, redness and swelling (inflammation).

KRYSTEXXA contains an enzyme called uricase that transforms the uric acid into a substance called

allantoin, which can be removed easily in the urine.

2.

What you need to know before you receive KRYSTEXXA

Do not use KRYSTEXXA

If you are allergic to pegloticase, or other uricases or any of the other ingredients of this

medicine (listed in section 6).

If you have a rare blood problem called glucose 6-phosphate dehydrogenase (G6PD) deficiency

or favism. Your doctor may test you for G6PD before you start KRYSTEXXA.

Warnings and precautions

Talk to your doctor or nurse before using KRYSTEXXA:

if you are currently taking other medicines to lower your uric acid level

if you have been told you have heart failure

if you have ever been told you have an enzyme deficiency that causes anaemia

if you weigh over 100 kg

if you have been treated with KRYSTEXXA before

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Monitoring during treatment

Your doctor will test your blood to measure uric acid levels before each dose to make sure that you

should continue receiving KRYSTEXXA.

Children and adolescents

KRYSTEXXA has not been studied in children or adolescents under 18 years of age. Therefore, this

medicine is not recommended in this age group.

Other medicines and KRYSTEXXA

Tell your doctor if you are taking, have recently taken or might take any other medicines. It is

especially important to tell your doctor if you are currently taking other urate-lowering medicines

(such as allopurinol or Febuxostat) or medicines containing polyethylene glycol (PEG) (such as

pegylated interferon or Doxorubicin). These medicines may put you at higher risk of infusion reaction.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor for advice before taking this medicine

.

Do not use KRYSTEXXA if you are pregnant or

breast-feeding, since it is not known how it will affect you or your baby.

Driving and using machines

KRYSTEXXA has little or no effect on your ability to drive. If you do not feel well, experience

symptoms such as dizziness or headache, or are tired after receiving KRYSTEXXA, you should not

drive or operate any machines.

KRYSTEXXA contains sodium

KRYSTEXXA contains 4.2 mg sodium per dose which means it is essentially sodium free.

3.

How to use KRYSTEXXA

KRYSTEXXA should be given to you by a doctor or nurse experienced in the treatment of severe

chronic gout in a healthcare centre.

How much KRYSTEXXA is given

The recommended dose of KRYSTEXXA is 8 mg. This dose is not adjusted for weight, age or kidney

disease.

Before you start treatment with KRYSTEXXA, your doctor may recommend that you take other

medicines (such as an antihistamine, paracetamol and a corticosteroid) to help reduce the risk that you

will get infusion-related reactions due to this treatment. Take these medicines as directed by your

doctor.

How KRYSTEXXA is administered

KRYSTEXXA is injected slowly into a vein (i.v. infusion) and your treatment will take about 2 hours

or sometimes longer. If you have a reaction during the infusion, your doctor may stop or adjust the

treatment. Your doctor may also ask you to wait after your treatment to be sure that you do not have

an infusion-related reaction.

You will receive KRYSTEXXA every 2 weeks.

If you stop taking KRYSTEXXA, and then are treated again, you may be at increased risk of infusion

reactions, including severe acute allergic reactions (anaphylaxis) so your doctor will monitor you

carefully when you restart treatment.

Your doctor will also test your blood to measure uric acid before your next dose to make sure that you

should continue receiving KRYSTEXXA.

Medicinal product no longer authorised

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The most

commonly reported serious side effects are: severe acute allergic reactions (

common

), infusion

reactions (

very common

), and gout flares (

very common

KRYSTEXXA will be administered by a doctor or nurse who will monitor you for side effects while

you receive KRYSTEXXA and for some time afterwards.

Severe allergic reactions (

common

) include fainting, sudden drop in blood pressure, and cardiac

arrest. Allergic reactions usually happen within 2 hours of the infusion, but may also happen at a later

time.

If you suddenly notice:

a swelling of the throat, tongue or other part of your body

tightness of the throat, hoarse voice or trouble swallowing

a shortness of breath, wheezing or breathing problems

a rash, itching or hives

tell your doctor or nurse IMMEDIATELY, since any of these may be signs of a serious allergic

reaction.

The most common signs and symptoms of local infusion reactions were: redness at the injection site,

itching, and rash. The most common signs and symptoms of generalised infusion reactions were:

hives, shortness of breath, redness in the face, sweating, chest discomfort or pain, chills, and high

blood pressure.

Allergic reactions may be more likely to occur in patients who weigh more than 100 kg.

An increase in gout flares is frequently observed when starting KRYSTEXXA. Your doctor may

prescribe medicines to reduce the likelihood of gout flares after starting KRYSTEXXA.

KRYSTEXXA does not need to be discontinued because of a gout flare.

Very common side effects

(may affect more than 1 in 10 people): hives, skin rash, itchy, dry or

irritated skin, nausea

Common side effects

(may affect up to 1 in 10 people): high blood sugar levels, vomiting, joint

swelling, flu-like symptoms

Uncommon side effects:

(may affect up to 1 in 100 people): worsening of a type of heart disease

called congestive heart failure, skin infection, elevated potassium levels in the blood

Frequency not known

(cannot be estimated from available data): destruction of red blood cells

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet.

5.

How to store KRYSTEXXA

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 label and the carton after EXP.

The expiry date refers to the last day of that month.

Medicinal product no longer authorised

This medicine will be stored in a healthcare facility where it is administered.

Store in a refrigerator (2°C to 8

Keep the vial in the outer carton in order to protect from light.

From a bacteriological point of view, the product should be used immediately. If the diluted solution is

not used immediately it can be stored refrigerated (2°C to 8°C). The solution should be used within 4

hours of dilution.

Do not use this medicine if you notice any particles or discolouration in the diluted solution.

6.

Contents of the pack and other information

What KRYSTEXXA contains

The active substance is pegloticase. Each vial contains 8 mg of pegloticase (8 mg/ml

concentrate).

The other ingredients are disodium hydrogen phosphate dihydrate, sodium dihydrogen

phosphate dihydrate, sodium chloride and water for injections.

What KRYSTEXXA looks like and contents of the pack

KRYSTEXXA 8 mg concentrate for solution for infusion is supplied in 2 ml glass vials containing

1 ml concentrate. KRYSTEXXA is a clear to slightly opalescent colourless solution.

Pack size of 1 vial.

Marketing Authorisation Holder

Crealta Pharmaceuticals Ireland Limited

Commercial House, Millbank Business Park, Lower Lucan Road, Lucan, Co. Dublin

Ireland

Manufacturer

United Drug, plc

United Drug House

Magna Business Park

Magna Drive, Citywest Road

Dublin 24

Ireland

This leaflet was last revised in {MM/YYYY}

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu.

------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

KRYSTEXXA must be prepared as follows:

Instructions for preparation of the solution for infusion:

KRYSTEXXA

vial should be visually inspected for particles and discolouration prior to dilution

and administration. Only solutions which are clear to slightly opalescent, colourless and free of

visible particles should be used.

Medicinal product no longer authorised

Appropriate aseptic technique should be used when preparing the infusion. The vial should not

be shaken.

1 ml of KRYSTEXXA should be withdrawn from the vial into a sterile syringe.

1 ml of KRYSTEXXA should be injected into a single 250 ml bag of sodium chloride

4.5 mg/ml (0.45%) or 9 mg/ml (0.9%) solution for injection or infusion.

The infusion bag containing the diluted KRYSTEXXA solution should be inverted a number of

times gently to ensure thorough mixing. The infusion bag containing diluted KRYSTEXXA

should not be shaken.

Before administration, the diluted solution of KRYSTEXXA should be allowed to reach room

temperature. KRYSTEXXA in a vial or in an intravenous infusion fluid must never be subjected

to artificial heating (e.g., hot water, microwave).

Any unused medicinal product or waste material must be disposed of in accordance with local

requirements.

Medicinal product no longer authorised

Annex IV

Scientific conclusions and grounds recommending the variation to the terms of the Marketing

Authorisation

Medicinal product no longer authorised

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR for pegloticase, the scientific

conclusions of CHMP are as follows:

Scientific conclusions and grounds for variation to the terms of the marketing authorisations

Reports of infusion related reactions or anaphylaxis coincident with

concomitant use of oral urate

lowering agents were submitted in this Periodic Safety Update Report, where infusion reactions in 28

cases and 9 cases with anaphylactic reactions were reported. As the development of these adverse

events may have been prevented in at least some of these cases if the patients would not have been

treated with concomitant urate lowering substances, an amendment of the summary of product

characteristics focusing on the importance of stopping treatment with uric acid lowering agents with

regard to masking the results of serum uric acid values (and therefore increasing the risk for infusion

reactions and anaphylactic reactions) should be implemented. The revised order of the two

corresponding paragraphs is to emphasize the correlation between concomitant medication with urate

lowering products and serum uric acid measurement. In addition, a further amendment regarding the

extension of the time of observation following the end of infusion from 1 hour to 2 hours as a

precautionary measure has been included along with a statement that delayed-type hypersensitivity

reactions have also been reported.

Therefore, in view of available data regarding anaphylaxis and infusion reactions, the

Pharmacovigilance Risk Assessment Committee considered that changes to the product information

were warranted.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds recommending the variation to the terms of the Marketing Authorisation

On the basis of the scientific conclusions for pegloticase the CHMP is of the opinion that the

benefit-risk balance of the medicinal product containing pegloticase is favourable subject to the

proposed changes to the product information

The CHMP recommends that the terms of the Marketing Authorisation(s) should be varied.

Medicinal product no longer authorised