ing treatment if levels increase to above 6 mg/dL. Because of the possibility that concomitant use of oral urate-lowering therapy and Krystexxa may potentially blunt the rise of serum uric acid levels, it is recommended that before starting Krystexxa patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while taking Krystexxa.
Infusion Reactions
During pre-marketing controlled clinical trials, infusion reactions were reported in 26% of patients treated with Krystexxa 8 mg every 2 weeks, and 41% of patients treated with Krystexxa 8 mg every 4 weeks, 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 Adverse 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 120 minutes. 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 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL. Because of the possibility that concomitant use of oral urate-lowering therapy and Krystexxa may potentially blunt the rise of serum uric acid levels, it is recommended that before starting Krystexxa patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while taking Krystexxa.
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 1 week before initiation of Krystexxa therapy and lasting at least 6 months, 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)]
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.
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 A |
