Pegloticase (Krystexxa)

Pegloticase is a pegylated enzyme containing a recombinant form of mammalian uricase enzyme derived from a genetically modified strain of E. coli. Pegloticase lowers uric acid by promoting the oxidation of uric acid to allantoin, which is then renally excreted. Pegloticase was initially approved in the U.S. in 2010.

Resources from Manufacturer

Krystexxa Connexxions Patient Support Program
Patient Medication Guide
Full Prescribing Information

Rheumatologic Indications and Dosing

Pegloticase is indicated for 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 (allopurinol, febuxostat) at the maximum medically appropriate dose or for whom these drugs are contraindicated.
  • Pegloticase is not recommended for the treatment of asymptomatic hyperuricemia.

Dosing

  • The recommended dose and regimen of pegloticase for adult patients is 8 mg (uricase protein) given as an intravenous infusion every two weeks.
  • The optimal treatment duration with pegloticase has not been established.

Contraindications

Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) should be screened before starting pegloticase.

Warnings and Precautions

  1. Anaphylaxis. During pre-marketing controlled clinical trials, anaphylaxis was reported with a frequency of 6.5% of patients treated with pegloticase every 2 weeks, compared to none with placebo.
    • Manifestations included wheezing, peri-oral or lingual edema, or hemodynamic instability, with or without rash or urticaria. Cases occurred in patients being pre-treated with one or more doses of an oral antihistamine, an intravenous corticosteroid and/or acetaminophen. This pre-treatment may have blunted or obscured symptoms or signs of anaphylaxis and therefore the reported frequency may be an underestimate.
    • Pegloticase should be administered in a healthcare setting by healthcare providers prepared to manage anaphylactic and infusion reactions. Patients should be pre-treated with antihistamines and corticosteroids. Pegloticase 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.
  2. Infusion Reactions. During pre-marketing controlled clinical trials, infusion reactions were reported in 26% of patients treated with pegloticase 8 mg every 2 weeks, and 41% of patients treated with pegloticase 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.
    • 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.
  3. Concomitant use of oral urate-lowering therapy. Because of the possibility that concomitant use of oral urate-lowering therapy and pegloticase may potentially blunt the rise of serum uric acid levels, it is recommended that before starting pegloticase patients discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while taking pegloticase.
  4. Gout Flares. Prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of pegloticase therapy and lasting at least 6 months, unless medically contraindicated or not tolerated. Pegloticase does not need to be discontinued because of a gout flare. The gout flare should be managed concurrently as appropriate for the individual patient.
  5. Congestive Heart Failure. Pegloticase has not been formally studied in patients with congestive heart failure, but some patients in the clinical trials experienced exacerbation. Exercise caution when using pegloticase in patients who have congestive heart failure and monitor patients closely following infusion.
  6. Re-treatment with pegloticase. No controlled trial data are available on the safety and efficacy of re-treatment with pegloticase after stopping treatment for longer than 4 weeks. Due to the immunogenicity of pegloticase, patients receiving re-treatment may be at increased risk of anaphylaxis and infusion reactions.

Adverse Reactions

Common side effects may include gout flares (77%), infusion reactions (26%), anti-pegloticase antibodies (92%), nausea, confusion, ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis, vomiting.

Pre-infusion Checklist

  1. Before starting pegloticase patients should discontinue oral urate-lowering medications and not institute therapy with oral urate-lowering agents while on pegloticase therapy.
  2. 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.
  3. Patients should receive pre-infusion medications (e.g. Antihistamines, corticosteroids), to minimize the risk of anaphylaxis and infusion reactions.

Medication Preparation

  1. Pegloticase 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.
  2. Pegloticase is a clear, colorless, sterile 8 mg/ml solution of pegloticase in a 2 ml single-use vial, expressed as amounts of uricase protein. Pegloticase must be diluted prior to use.
  3. Visually inspect pegloticase for particulate matter and discoloration before administration, whenever solution and container permit. Do not use vials if either is present.
  4. Use appropriate aseptic technique. Withdraw 1 ml of pegloticase 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.
  5. Invert the infusion bag containing the dilute pegloticase solution a number of times to ensure thorough mixing. Do not shake.
  6. Pegloticase diluted in infusion bags is stable for 4 hours at 2º to 8ºC (36º to 46ºF) and at room temperature (20º to 25ºC, 68º to 77ºF). However it is recommended that diluted solutions be stored under refrigeration, not frozen, protected from light, and used within 4 hours of dilution.
  7. Before administration, allow the diluted solution of pegloticase to reach room temperature. Pegloticase in a vial or in an intravenous infusion fluid should never be subjected to artificial heating (e.g., hot water, microwave).

Medication Administration and Monitoring

The pegloticase admixture should only be administered by intravenous infusion over no less than 120 minutes via gravity feed, syringe-type pump, or infusion pump. Do not administer as an intravenous push or bolus.

Managing Infusion Reactions

If an infusion reaction occurs during the administration of pegloticase, the infusion may be slowed, or stopped and restarted at a slower rate, at the discretion of the attending health care professional. Since infusion reactions can occur after completion of infusion, observation of patients for approximately an hour post-infusion should be considered.

Additional Information

  • Pregnancy Category C: A complete evaluation of the reproductive and developmental toxicity of pegloticase has not been completed. It is not known whether pegloticase can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.
  • Nursing Mothers: It is not known whether this drug is excreted in human milk.
  • Pediatric Use: The safety and effectiveness of pegloticase in pediatric patients less than 18 years of age have not been established.
  • Geriatric Use: Of the total number of patients treated with pegloticase 8 mg every 2 weeks in the controlled studies, 34% (29 of 85) were 65 years of age and older and 12% (10 of 85) were 75 years of age and older. No overall differences in safety or effectiveness were observed between older and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dose adjustment is needed for patients 65 years of age and older.
  • Renal Impairment: No dose adjustment is required for patients with renal impairment.
  • Over Dosage: No reports of over dosage with pegloticase have been reported. The maximum dose that has been administered as a single intravenous dose is 12 mg as uricase protein. Patients suspected of receiving an overdose should be monitored, and general supportive measures should be initiated as no specific antidote has been identified.

Updated March 2018 - ARHP Practice Committee

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The information contained in this biologic reference guide is offered solely for purposes of providing health care professionals with a quick and initial reference. Before prescribing or administering any drug contained in this biologic reference guide, health professionals should read the manufacturer’s complete prescribing information in order to be informed of the various clinical considerations to be taken into account. The American College of Rheumatology is providing this information as a benefit and service in furtherance of its educational mission. By providing this information, ACR is not endorsing or recommending any of the listed companies or any of their drugs or other products. The information contained in the biologic reference guides reflect the conclusions of the individual companies and not those of the ACR which specifically disclaims any responsibility or liability for the use of such information and/or for the performance of any of the drugs listed in this biologic reference guide.