Pegloticase

Renal Impairment No dose adjustment is required for patients with renal impairment. In a 52-week, randomized, double-blind trial which evaluated KRYSTEXXA co-administered with methotrexate compared to KRYSTEXXA alone, 85% of patients had chronic kidney disease based on estimated glomerular filtration rate (eGFR) of ≥ 40 to < 90 mL/min/1.73m 2 at baseline.

In the pre-marketing 24-week controlled clinical trials with KRYSTEXXA alone, a total of 32% (27 of 85) of subjects treated with KRYSTEXXA 8 mg every 2 weeks had a creatinine clearance of ≤ 62.5 mL/min. No overall differences in efficacy were observed.

Important Administration Instructions Precautions Prior to Treatment It is recommended that before starting KRYSTEXXA patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while patients are on KRYSTEXXA therapy. Monitoring Therapy: The risk of infusion reactions, including anaphylaxis, is higher in patients who have lost therapeutic response.

Monitor serum uric acid levels prior to each infusion and discontinue treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed [see Warnings and Precautions (5.1 , 5.2) ]. Infusion Reaction Precautions KRYSTEXXA should be administered in a healthcare setting by healthcare providers prepared to manage infusion reactions, including anaphylaxis.

Observe patients for an appropriate period of time after administration [see Warnings and Precautions (5.1 , 5.2) ]. Patients should receive pre-infusion medications (e.g., antihistamines, corticosteroids), to minimize the risk of infusion reactions, including anaphylaxis. 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 , Adverse Reactions ]. Administration Precautions Do not administer KRYSTEXXA as an intravenous push or bolus. KRYSTEXXA should only be administered by intravenous infusion.

An infusion pump may be used for the Ready-to-Use vial. Gravity feed, syringe-type pump, or infusion pump may be used for the To-Be-Diluted vial [see Dosage and Administration ] .

Recommended Dosage and Administration The recommended dosage is KRYSTEXXA 8 mg given as an intravenous infusion every two weeks, co-administered with weekly oral methotrexate 15 mg and folic acid or folinic acid supplementation. KRYSTEXXA alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate.

If co-administering with methotrexate, start weekly methotrexate and folic acid or folinic acid supplementation at least 4 weeks prior to initiating, and throughout treatment with KRYSTEXXA [see Clinical Studies ] . Refer to the Full Prescribing Information for methotrexate. The optimal treatment duration with KRYSTEXXA has not been established.

Preparation and Administration Instructions KRYSTEXXA injection is supplied as either a Ready-to-Use single-dose vial (with hanger label) or a To-be-Diluted single-dose vial. Ready-to-Use KRYSTEXXA 8 mg/50 mL (0.16 mg/mL) single-dose vial (with hanger label) Step 1: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use vial if either is present. Step 2: Allow the Ready-to-Use vial to reach room temperature at 20°C to 25°C (68°F to 77°F). KRYSTEXXA in a vial should never be subjected to artificial heating (e.g., hot water, microwave). Unopened vial may be stored for up to 4 hours at room temperature. Step 3: Use appropriate aseptic technique.

Insert a vented intravenous set through the septum of the vial. Once the stopper is punctured, use immediately. Step 4: To administer, invert and hang the vial utilizing the built-in hanger label affixed to the bottom of the vial. Step 5: Administer as an intravenous infusion over a period of no less than 120 minutes using an infusion pump.

After the entire contents of the vial have been administered, flush the injection line with Sodium Chloride Injection to ensure delivery of the required dose. To-be-Diluted KRYSTEXXA 8 mg/mL single-dose vial Step 1: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use vial if either is present. Step 2: Use appropriate aseptic technique. Withdraw 1 mL of KRYSTEXXA (To-be-Diluted) from the vial into a sterile syringe. Discard any unused portion of product remaining in the 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. Step 3: Gently invert the infusion bag containing the dilute KRYSTEXXA solution a number of times to ensure thorough mixing. Do not shake. Step 4: 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).

KRYSTEXXA diluted in infusion bags is stable for 4 hours at 2°C to 8°C (36°F to 46°F) and at room temperature at 20°C to 25°C (68°F 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 ].

Step 5: Administer as an intravenous infusion over 120 minutes using gravity feed, syringe-type pump, or infusion pump.