Pegloticase

KRYSTEXXA ® (pegloticase) is indicated, for the treatment of chronic gout in adult patients refractory to conventional therapy. Gout refractory to conventional therapy occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated. KRYSTEXXA ® (pegloticase) is a PEGylated uric acid specific enzyme indicated for the treatment of chronic gout in adult patients refractory to conventional therapy. Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.

KRYSTEXXA is a uric acid specific enzyme which is a recombinant uricase and achieves its therapeutic effect by catalyzing the oxidation of uric acid to allantoin, thereby lowering serum uric acid. Allantoin is an inert and water-soluble purine metabolite, it is readily eliminated, primarily by renal excretion.

Recommended Dosage The recommended dosage is KRYSTEXXA 8 mg every two weeks given as an intravenous infusion, co-administered with weekly methotrexate 15 mg orally. KRYSTEXXA alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate. Methotrexate with folic acid or folinic acid supplementation should be initiated at least 4 weeks prior to initiating, and throughout treatment with KRYSTEXXA. Discontinue oral urate-lowering agents before starting KRYSTEXXA. Monitor serum uric acid levels before each infusion. Pre-medicate patients with antihistamines and corticosteroids. Preparation and Administration Do not administer as an intravenous push or bolus. KRYSTEXXA injection is supplied as a Ready-to-Use (with hanger label) single-dose vial or a To-be-Diluted single-dose vial.

KRYSTEXXA is contraindicated in: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Boxed warning (anaphylaxis and infusion reactions, g6pd deficiency associated hemolysis and methemoglobinemia): Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA. Anaphylaxis may occur with any infusion, and generally manifests within 2 hours of the infusion. However, delayed hypersensitivity reactions have also been reported. Anaphylaxis: Anaphylaxis may occur with any KRYSTEXXA infusion. Pre-medicate and monitor patients. Infusion Reactions: Infusion reactions occurred in patients treated with KRYSTEXXA. G6PD Deficiency Associated Hemolysis and Methemoglobinemia: Screen patients at risk for G6PD deficiency. Do not administer KRYSTEXXA to patients with G6PD deficiency. Gout Flares: Gout flare prophylaxis is recommended for at least the first 6 months of KRYSTEXXA therapy.

The following serious adverse reactions are discussed in greater detail in other sections of the label: Anaphylaxis Infusion Reactions G6PD Deficiency Associated Hemolysis and Methemoglobinemia Gout Flares Congestive Heart Failure Co-administration with methotrexate: The most common adverse reactions (≥ 5% of patients) are gout flares, arthralgia, COVID-19, nausea and fatigue. KRYSTEXXA alone: The most common adverse reactions (≥ 5% of patients) are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.

Methotrexate KRYSTEXXA 8 mg every 2 weeks has been studied in patients with chronic gout refractory to conventional therapy taking concomitant oral methotrexate 15 mg weekly. Co-administration of methotrexate with KRYSTEXXA may increase pegloticase concentration compared to KRYSTEXXA alone.

Before the preparation for use, KRYSTEXXA must be stored in the carton and maintained at all times under refrigeration between 2°C to 8°C (36°F to 46°F). Do not shake or freeze. Protect from light.