f anaphylaxis and infusion reactions. Administer KRYSTEXXA in a healthcare setting and by healthcare providers prepared to manage anaphylaxis and infusion reactions, and observe patients for an appropriate period of time after administration. [see Warnings and Precautions (5.1, 5.2)]
If an infusion reaction occurs during the administration of KRYSTEXXA, the infusion may be slowed, or stopped and restarted at a slower rate, at the discretion of the physician. Since infusion reactions can occur after completion of infusion, observation of patients for approximately an hour post-infusion should be considered. [see Warnings and Precautions (5.2), Adverse Reactions (6.1)]
3 DOSAGE
KRYSTEXXA is a clear, colorless, sterile 8mg/mL solution of pegloticase in a 2mL single-use vial, expressed as amounts of uricase protein. KRYSTEXXA must be diluted prior to use.
4 CONTRAINDICATIONS
Glucose-6-phosphate dehydrogenase (G6PD) deficiency: KRYSTEXXA is contraindicated in patients with G6PD deficiency due to the risk of hemolysis and methemoglobinemia. It is recommended that patients at higher risk for G6PD deficiency (e.g.,patients of African or Mediterranean ancestry) be screened for G6PD deficiency before starting KRYSTEXXA.
5 WARNINGS AND PRECAUTIONS
5.1 Anaphylaxis
During pre-marketing controlled clinical trials, anaphylaxis was reported with a frequency of 6.5% of patients treated with KRYSTEXXA every 2weeks, compared to none with placebo. Manifestations included wheezing, peri-oral or lingual edema, or hemodynamic instability, with or without rash or urticaria. Cases occurred in patients being pre-treated with one or more doses of an oral antihistamine, an intravenous corticosteroid and/or acetaminophen. This pre-treatment may have blunted or obscured symptoms or signs of anaphylaxis and therefore the reported frequency may be an underestimate. [See Adverse Reactions (6)]
KRYSTEXXA should be administered in a healthcare setting by healthcare providers prepared to manage anaphylaxis. Patients should be pre-treated with antihistamines and corticosteroids. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2hours of the infusion. However, delayed type hypersensitivity reactions have also been reported. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA. Patients should be informed of the symptoms and signs of anaphylaxis and instructed to seek immediate medical care should anaphylaxis occur after discharge from the healthcare setting.
The risk of anaphylaxis is higher in patients whose uric acid level increases to above 6mg/dL, particularly when 2consecutive levels above 6mg/dL are observed. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6mg/dL.
5.2 Infusion Reactions
During pre-marketing controlled clinical trials, infusion reactions were reported in 26% of patients treated with KRYSTEXXA 8mg every 2weeks, and 41% of patients treated with KRYSTEXXA 8mg every 4weeks, compared to 5% of patients treated with placebo. These infusion reactions occurred in patients being pre-treated with an oral antihistamine, intravenous corticosteroid and/or acetaminophen. This pre-treatment may have blunted or obscured symptoms or signs of infusion reactions and therefore the reported frequency may be an underestimate. [See Advers |
