pegloticase (Rx)

>10%

Gout flares (77%)

Infusion reactions (26%)

Nausea (12%)

Urticaria (10.6%)

1-10%

Chest discomfort (9.5%)

Chest pain (9.5%)

Erythema (9.5%)

Pruritus (9.5%)

Nasopharyngitis (7%)

Anaphylaxis (5%)

Postmarketing Reports

Hemolysis and methemoglobinemia in patients with G6PD deficiency

Congestive heart failure

Asthenia

Malaise

Peripheral swelling

Contraindications

History of serious hypersensitivity, including anaphylaxis, to pegloticase or its components

G6PD-deficiency (increased risk of hemolysis and methemoglobinemia)

Cautions

Life threatening hemolytic reactions and methemoglobinemia reported with G6PD deficiency; screen patients at risk for G6PD deficiency before initiating (eg, patients of African, Mediterranean [including Southern European and Middle Eastern], and Southern Asian ancestry); do not administer to patients with G6PD deficiency

Gout flares may occur after initiating owing to changing serum uric acid levels resulting in mobilization of urate from tissue deposits; gout flare prophylaxis with an NSAID or colchicine is recommended starting at least 1 week before starting and during pegloticase treatment and for at least 6 months, unless medically contraindicated or not tolerated

Exacerbation of pre-existing CHF reported; exercise caution when using this drug in patients who have congestive heart failure and monitor patients closely following infusion

No controlled trial data are available regarding safety and efficacy of retreatment with pegloticase after stopping treatment for >4 weeks; owing to immunogenicity of pegloticase, patients receiving retreatment may be at increased risk of anaphylaxis and infusion reactions

Anaphylaxis

• Anaphylaxis reported; pretreat with antihistamines and corticosteroids before each infusion; risk increased with uric acid level >6 mg/dL (especially when 2 consecutive level >6 mg/dL observed); monitor serum uric acid levels prior to infusions and discontinue treatment if levels increase to above 6 mg/dL
• Therapy 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 2 hr of the infusion; however, delayed-type hypersensitivity reactions have also been reported
• Patients should be closely monitored for appropriate period of time for anaphylaxis after administration of the drug; 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

Infusion reactions

• Infusion reactions may occur; manifestations include urticaria, dyspnea, chest discomfort, chest pain, erythema, and pruritus (symptoms overlap with anaphylaxis); risk of infusion reactions increased with uric acid level >6 mg/dL; monitor serum uric acid levels prior to infusions and discontinue treatment if levels increase to above 6 mg/dL
• Because of the possibility that concomitant use of oral urate-lowering therapy and this medication may potentially blunt the rise of serum uric acid levels, it is recommended that before starting therapy patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while taking this medication

Pregnancy

There are no adequate and well-controlled studies in pregnant women

Animal data

• No structural abnormalities were observed on animal reproduction studies, when pegloticase administered by subcutaneous injection to pregnant rats and rabbits during period of organogenesis at doses up to 50 and 75 times, respectively, the maximum recommended human dose (MRHD); decreases in mean fetal and pup body weights were observed at approximately 50 and 75 times MRHD, respectively

Lactation

Not known whether drug is excreted in human milk; drug should not be used when breastfeeding unless clear benefit to mother can overcome unknown risk to newborn/infant.

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant, pegylated uric acid specific enzyme; achieves its therapeutic effect by catalyzing oxidation of uric acid to allantoin, thereby lowering serum uric acid levels

Pharmacokinetics

Onset of action: 24 hr

Duration: 12.5 days

Half-life: 14 days

IV Compatibilities

Solution: 0.9% NaCl, 0.45% NaCl

IV Preparation

IV infusion

• Withdraw 1 mL from vial (discard any unused portion) and add to a single 250 mL bag of 0.9% or 0.45% NaCl
• Invert infusion bag a number of times to ensure thorough mixing
• DO NOT SHAKE
• Stable for 4 hr at room temperature (20-25ºC [68-77ºF]); however, recommended to store refrigerated and use within 4 hr

IV Administration

Do NOT administer as IV push or bolus

Premedicate with antihistamines and corticosteroids

Administer IV infusion over at least 2 hr via gravity feed or volumetric infusion pump

If an infusion reaction occurs, may slow, or stop and restart infusion at slower rate, at the discretion of the physician

Infusion reactions can occur after completion; observe patient ~1 hr post-infusion

Storage

Protect from light

Do not shake

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF) in original carton

Admixture

• Recommended to refrigerate at 2-8ºC (36-46ºF)
• May store at room temperature (20-25ºC [68-77ºF])
• Use within 4 hr