Krystexxa

Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of severe refractory chronic gout. The medicinal product should be administered in a healthcare setting and by healthcare professionals prepared to manage anaphylaxis and infusion reactions.

Close monitoring is required during the infusion and for at least 2 hours after the end of the infusion. Availability of resuscitation equipment must be ensured. Delayed-type hypersensitivity reactions have also been reported. Posology The recommended dose is 8 mg pegloticase given as an intravenous infusion every two weeks.

g. Medicinal product no longer authorised 3 Monitoring of serum uric acid level is required prior to each infusion. 4). 4). 4). The duration of treatment should be based upon maintenance of response (serum uric acid levels < 6 mg/dl) and clinical judgment.

2). 2). Paediatric population The safety and efficacy of KRYSTEXXA in children and adolescents aged below 18 years has not been established. No data are available. 9%), is administered as an intravenous infusion over no less than 2 hours, at a flow rate of approximately 2 ml/minute.

6.

5% (8/123) in patients treated with 8 mg every 2 weeks; infusion reactions, which occurred at a frequency of 26% and gout flares, which were more common during the first 3 months of treatment. Tabulated list of adverse reactions The following convention has been used for classification of the adverse reactions reported in the Phase 3 clinical trials (see Table 1 below): very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Medicinal product no longer authorised 6 Table 1. Adverse Reactions System Organ Class Adverse Reaction Metabolism and nutrition disorders Common: Hyperglycaemia Uncommon: Hyperkalaemia Cardiac disorders Uncommon: Exacerbation of congestive heart failure Gastrointestinal disorders Very common: Nausea Common: Vomiting Skin and subcutaneous disorders Very common: Dermatitis, urticaria, pruritus, skin irritation, dry skin Uncommon: Cellulitis Musculoskeletal and connective tissue disorders Very common: Gout flare Common: Joint swelling Blood and lymphatic disorders Not known: Haemolysis General disorders and administration site conditions Very common: Infusion related reaction Common: Anaphylaxis, influenza like illness Description of selected adverse reactions Infusion-related reactions Infusion-related reactions can occur after initiation of any infusion, in spite of patients being pre- medicated with oral antihistamine, intravenous corticosteroid and/or paracetamol, and generally during or within 1 hour after the infusion is completed.

The first infusion reaction usually occurs after the 2nd to 4th infusion. The most common signs and symptoms of local infusion reactions are: erythema, pruritus, and rash. The most common signs and symptoms of systemic infusion reactions are: urticaria, dyspnoea, flushing, hyperhidrosis, chest discomfort or pain, chills, and hypertension.

The benefit/risk balance should be assessed for each individual patient on an on-going basis considering the effect on tophus resolution as well as the risk of infusion reactions, gout flares, and potentially increased cardiac risk.

The long-term risk of prophylactic medications to prevent infusion reactions, such as glucocorticoids, should also be taken into consideration. The data for long-term treatment from controlled clinical studies are limited. This should be considered when the decision is made for a therapy longer than 6 months.

Infusion-related reactions / Anaphylaxis KRYSTEXXA can induce severe allergic responses, including anaphylactic shock with cardiac arrest. Special attention is recommended for patients with pre-existing cardiopulmonary disease. 8). If an infusion reactionMedicinal product no longer authorised 4 occurs during the administration, the infusion may be slowed, or stopped and restarted at a slower rate, at the discretion of the physician.

e. when serum uric acid values were above 6 mg/dl (360 μmol/L). Therefore, monitoring of serum uric acid level is required prior to each infusion. KRYSTEXXA should be discontinued if 2 consecutive levels above 6 mg/dl have been measured.

Since concomitant use of oral urate-lowering therapy may potentially mask the rise of serum uric acid associated with the loss of response, patients taking concomitant oral urate-lowering therapy may be at increased risk of infusion reactions and/or anaphylaxis.

It is therefore recommended to discontinue oral urate-lowering medications before starting treatment and not institute therapy with oral urate- lowering agents while taking KRYSTEXXA. Acute gouty attacks (gout flare) An increase in gout flares is frequently observed upon treatment initiation, probably as a result of mobilization of urate from tissue deposits.

To reduce the likelihood of gout flares after initiation of KRYSTEXXA prophylaxis with colchicine or a non-steroidal anti-inflammatory drug (NSAID) is recommended. It is recommended to start this treatment 1 week before initiation of KRYSTEXXA and continue for at least 6 months, unless medically contraindicated or not tolerated.

1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and other cellular metabolic disorders known to cause haemolysis and methemoglobinemia. , patients of African or Mediterranean ancestry) should be screened for G6PD deficiency before starting KRYSTEXXA.