KRYSTEXXA™ (pegloticase)

KRYSTEXXA is intended for intravenous infusion.

KRYSTEXXA is a sterile, clear, colorless solution containing 8 mg/mL pegloticase in phosphate-buffered saline.

KRYSTEXXA (pegloticase) concentrations are expressed as concentrations of uricase protein. Each mL of KRYSTEXXA contains 8 mg of uricase protein (conjugated to 24 mg of 10 kDa mPEG), 2.18 mg Disodium Hydrogen Phosphate Dihydrate (Na2HPO4•2H2O), 8.77 mg Sodium Chloride (NaCl), 0.43 mg Sodium Dihydrogen Phosphate Dihydrate (NaH2PO4•2H2O), and Water for Injection to deliver 8 mg of pegloticase (as uricase protein).

KRYSTEXXA™ (pegloticase) is a PEGylated uric acid specific enzyme 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.

Important Limitations of Use:
KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.

• Anaphylaxis: Anaphylaxis occurred in patients treated with KRYSTEXXA. Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. However, delayed-type hypersensitivity reactions have also been reported. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis. Patients should be pre-medicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA.
• Infusion Reactions: Infusion reactions occurred in patients treated with KRYSTEXXA. KRYSTEXXA should be administered in a healthcare setting and by healthcare providers prepared to manage infusion reactions. Patients should be pre-medicated with antihistamines and corticosteroids. Monitor patients closely for signs and symptoms of infusion reactions. In the event of an infusion reaction, the infusion should be slowed, or stopped and restarted at a slower rate. If a severe infusion reaction occurs, discontinue infusion and institute treatment as needed. The risk of an infusion reaction is higher in patients who have lost therapeutic response.
• Gout Flares: An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including treatment with KRYSTEXXA. If a gout flare occurs during treatment, KRYSTEXXA need not be discontinued. Gout flare prophylaxis (i.e., non-steroidal anti-inflammatory drugs [NSAID] or colchicine upon initiation of treatment) is recommended for at least the first 6 months of therapy unless medically contraindicated or not tolerated.
• Congestive Heart Failure: KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.

The most common adverse reactions (occurring in at least 5% of KRYSTEXXA-treated patients) are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.

To report SUSPECTED ADVERSE REACTIONS, contact Savient Pharmaceuticals, Inc. at 1-888-579-7839 (1-888-KRYSTEXXA) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Dosage
The recommended dose and regimen of KRYSTEXXA for adult patients is 8 mg (uricase protein) given as an intravenous infusion every two weeks.

The optimal treatment duration with KRYSTEXXA has not been established.

Preparation
Visually inspect KRYSTEXXA for particulate matter and discoloration before administration, whenever solution and container permit. Do not use vials if either is present.

Use appropriate aseptic technique. Withdraw 1 mL of KRYSTEXXA from the vial into a sterile syringe. Discard any unused portion of product remaining in the 2 mL vial. Inject into a single 250 mL bag of 0.9% Sodium Chloride Injection, USP or 0.45% Sodium Chloride Injection, USP for intravenous infusion. Do not mix or dilute with other drugs.

Invert the infusion bag containing the dilute KRYSTEXXA solution a number of times to ensure thorough mixing. Do not shake.

KRYSTEXXA diluted in infusion bags is stable for 4 hours at 2° to 8°C (36° to 46°F) and at room temperature (20° to 25°C, 68° to 77°F). However it is recommended that diluted solutions be stored under refrigeration, not frozen, protected from light, and used within 4 hours of dilution. [see How Supplied/Storage and Handling]

Before administration, allow the diluted solution of KRYSTEXXA to reach room temperature. KRYSTEXXA in a vial or in an intravenous infusion fluid should never be subjected to artificial heating (e.g., hot water, microwave).

Administration
Do not administer as an intravenous push or bolus.

Monitoring Therapy: The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response. Monitor serum uric acid levels prior to infusions and consider discontinuing treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.

The KRYSTEXXA admixture should only be administered by intravenous infusion over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump.

Patients should receive pre-infusion medications (e.g. antihistamines, corticosteroids), to minimize the risk of 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.

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.

How Supplied

KRYSTEXXA is supplied as a clear, colorless, sterile solution in phosphate buffered saline intended for intravenous infusion after dilution. KRYSTEXXA is supplied in a single-use 2 mL glass vial with a Teflon® coated (latex-free) rubber injection stopper to deliver KRYSTEXXA as 8 mg of uricase protein in 1 mL volume.

Storage and Handling

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

Do not use beyond the expiration date stamped.

NDC# 54396-801-01

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Code #: 1801
Issued September 2010
Last Modified: September 2010
©2010 Savient Pharmaceuticals, Inc.