e Reactions (6)]
KRYSTEXXA should be administered in a healthcare setting by healthcare providers prepared to manage infusion reactions. Patients should be pre-treated with antihistamines and corticosteroids. KRYSTEXXA should be infused slowly over no less than 120minutes. In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate.
The risk of infusion reaction 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.
5.3 Gout Flares
Gout flares may occur after initiation of KRYSTEXXA. [see Adverse Reactions (6.1)] An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1week before initiation of KRYSTEXXA therapy and lasting at least 6months, unless medically contraindicated or not tolerated. KRYSTEXXA does not need to be discontinued because of a gout flare. The gout flare should be managed concurrently as appropriate for the individual patient. [see Dosage and Administration (2)]
5.4 Congestive Heart Failure
KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in the clinical trials experienced exacerbation. [see Adverse Reactions (6.1)] Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.
5.5 Re-treatment with KRYSTEXXA
No controlled trial data are available on the safety and efficacy of re-treatment with KRYSTEXXA after stopping treatment for longer than 4 weeks. Due to the immunogenicity of KRYSTEXXA, patients receiving re-treatment may be at increased risk of anaphylaxis and infusion reactions. Therefore, patients receiving re-treatment after a drug-free interval should be monitored carefully. [see Adverse Reactions (6.2)]
6 ADVERSE REACTIONS
The most commonly reported serious adverse reactions from pre-marketing controlled clinical trials were anaphylaxis, which occurred at a frequency of 6.5% in patients treated with KRYSTEXXA 8mg every 2weeks, compared to none with placebo; infusion reactions, which occurred at a frequency of 26% in patients treated with KRYSTEXXA 8mg every 2weeks, compared to 5% treated with placebo; and gout flares, which were more common during the first 3months of treatment with KRYSTEXXA compared with placebo. All patients in pre-marketing controlled clinical trials were pre-treated with an oral antihistamine, intravenous corticosteroid and/or acetaminophen to prevent anaphylaxis and infusion reaction. Patients also received non-steroidal anti-inflammatory drugs or colchicine, or both, for at least 7days as gout flare prophylaxis before beginning KRYSTEXXA treatment. [seeBoxed Warning, Warnings and Precautions (5.1, 5.2, 5.3)]
6.1 Clinical Trials Experience
The data described below reflect exposure to KRYSTEXXA in patients with chronic gout refractory to conventional therapy in two replicate randomized, placebo-controlled, double-blind 6-month clinical trials: 85patients were treated with KRYSTEXXA 8mg every 2weeks; 84patients |
