Usual Adult Dose for Gout

8 mg via IV infusion every 2 weeks

Comment:

• Must be given via IV infusion (over no less than 120 minutes); do not administer IV push or bolus.
• Premedications (e.g., antihistamines, corticosteroids) are recommended to minimize the risk of anaphylaxis and infusion reactions.
• This drug is not recommended for the treatment of asymptomatic hyperuricemia.
• The optimal duration of treatment has not been established.

Use: For the treatment of chronic gout in patients who are refractory to conventional therapy (e.g., patients who have failed to normalize serum uric acid and whose signs/symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated)

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Data not available

Dose Adjustments

To Decrease Risk of Anaphylaxis and Infusion Reactions:

• Premedicate with antihistamines and corticosteroids
• Discontinue oral urate lowering medications and do not institute these agents during treatment
• Monitor serum uric acid levels prior to each infusion; consider discontinuing treatment if levels are greater than 6 mg/dL, especially if 2 consecutive levels exceed 6 mg/dL
• If an infusion reaction occurs during administration, infusion may be slowed or stopped and restarted at a slower rate as appropriate
• The safety and efficacy of retreatment with this drug after stopping treatment for more than 4 weeks is unknown. If this drug is restarted after a drug-free interval, patients may be at an increased risk of anaphylaxis and infusion reactions and should be monitored carefully.

Precautions

US BOXED WARNINGS: ANAPHYLAXIS AND INFUSION REACTIONS:

• Anaphylaxis and infusion reactions have been reported to occur during and after administration of this drug.
• 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.
• This drug should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.
• Patients should be premedicated with antihistamines and corticosteroids.
• Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration.
• 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.

GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA:

• Screen patients at risk for G6PD deficiency prior to starting this drug.
• Hemolysis and methemoglobinemia have been reported with this drug in patients with G6PD deficiency.
• Do not administer this drug to patients with G6PD deficiency.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer in a healthcare setting by healthcare providers equipped to manage anaphylaxis and infusion reactions
• Premedicate with antihistamines and corticosteroids
• Administer as IV infusion over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump; do not give as an IV push or bolus
• If an infusion reaction occurs, the infusion should be slowed or stopped and restarted at a slower rate.

Reconstitution/preparation techniques:

• Withdraw 1 mL (8 mg) of pegloticase (uricase protein) from vial and inject into 250 mL bag of NS or 0.45% NS
• Invert infusion bag gently to ensure thorough mixing; do not shake

Storage requirements:
Prior to dilution: Store in carton, protect from light, keep under refrigeration (2C to 8C [36F to 46F]) at all times; do not shake or freeze.

• Following dilution in infusion bag: Stable for 4 hours at 2C to 8C (36F to 46F) and at room temperature 20C to 25C (68F to 77F); however, if storage is necessary, preferred storage is refrigeration; protect from light; use within 4 hours of dilution
• Allow diluted solutions to reach room temperature prior to administration; do not subject vial or diluted solution to artificial heating (e.g. hot water, microwave)

IV compatibility:

• Do not mix or dilute with other drugs

General:

• Patients should receive gout flare prophylaxis starting at least 1 week before initiating therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.
• The risk of anaphylaxis and infusion reactions is higher in patients who have lost therapeutic response, therefore, monitor serum uric acid levels prior to each infusion and consider discontinuing treatment if levels are greater than 6 mg/dL, especially if 2 consecutive levels exceed 6 mg/dL.
• Prior to initiating therapy, patients should discontinue oral urate-lowering medications and not restart on these agents while receiving this drug as these agents may blunt the rise of serum uric acid levels.

Monitoring:

• Screen for G6PD deficiency before starting therapy
• Monitor serum uric acid levels prior to each infusion
• Monitor for anaphylaxis and infusion reactions

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Inform patients of the risk of serious hypersensitivity reactions and infusion reactions and explain to patients the importance of adhering to their treatment plan to help prevent or lessen the severity of these reactions.
• Patients should be aware of the most common signs and symptoms of hypersensitivity and infusion reactions and should be instructed to report these symptoms promptly should they occur during or after an infusion.
• Patients should be told to immediately seek medical treatment if hypersensitivity reactions occur after an infusion.
• Patients should understand that gout flares may increase when starting therapy and they should not stop this medication if they experience a flare.