Krystexxa
pegloticase
Medicinal product no longer authorised
pegloticase
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 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
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.
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.
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.
Your doctor will test your blood to measure uric acid levels before each dose to make sure that you should continue receiving KRYSTEXXA.
Medicinal product no longer authorised
KRYSTEXXA has not been studied in children or adolescents under 18 years of age. Therefore, this medicine is not recommended in this age group.
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.
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.
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 4.2 mg sodium per dose which means it is essentially sodium free.
KRYSTEXXA should be given to you by a doctor or nurse experienced in the treatment of severe chronic gout in a healthcare centre.
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.
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.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
Medicinal product no longer authorised
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.
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
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.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
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.
This medicine will be stored in a healthcare facility where it is administered.
Store in a refrigerator (2°C to 8C).
Medicinal product no longer authorised
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.
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.
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.
Crealta Pharmaceuticals Ireland Limited
Commercial House, Millbank Business Park, Lower Lucan Road, Lucan, Co. Dublin Ireland
Magna Drive, Citywest Road Dublin 24
Ireland
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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.
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
Medicinal product no longer authorised
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
Medicinal product no longer authorised
Taking into account the PRAC Assessment Report on the PSUR for pegloticase, the scientific conclusions of CHMP are as follows:
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.
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.