Pegloticase

KRYSTEXXA is a uric acid specific enzyme which is a recombinant uricase and achieves its therapeutic effect by catalyzing the oxidation of uric acid to allantoin, thereby lowering serum uric acid. Allantoin is an inert and water-soluble purine metabolite; it is readily eliminated, primarily by renal excretion.

• KRYSTEXXA ® (pegloticase) is 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.ICD-10: M10.9

• KRYSTEXXA is contraindicated in: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency [see Warnings and Precautions (5.3) ]. Patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components.contraindicated

Recommended Dosage The recommended dosage is KRYSTEXXA 8 mg every two weeks given as an intravenous infusion, co-administered with weekly methotrexate 15 mg orally. KRYSTEXXA alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate. ( 2.2 ) Methotrexate with folic acid or folinic acid supplementation should be initiated at least 4 weeks prior to initiating, and throughout treatment with KRYSTEXXA. ( 2.2 ) Discontinue oral urate-lowering agents before starting KRYSTEXXA. ( 2.1 ) Monitor serum uric acid levels before each infusion. ( 2.1 ) Pre-medicate patients with antihistamines and corticosteroids. ( 2.1 , 5.1 , 5.2 ) Preparation and Administration Do not administer as an intravenous push or bolus. ( 2.1 ) KRYSTEXXA injection is supplied as a Ready-to-Use (with hanger label) single-dose vial or a To-be-Diluted single-dose vial. ( 2.3 ) See full prescribing information for information on preparation and administration for each vial presentation. ( 2.1 , 2.2 , 2.3 ) 2.1 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.

Anaphylaxis : Anaphylaxis may occur with any KRYSTEXXA infusion. Pre-medicate and monitor patients. ( 5.1 ) Infusion Reactions : Infusion reactions occurred in patients treated with KRYSTEXXA. Pre-medicate and monitor patients. ( 5.2 ) G6PD Deficiency Associated Hemolysis and Methemoglobinemia : Screen patients at risk for G6PD deficiency. Do not administer KRYSTEXXA to patients with G6PD deficiency. ( 5.3 ) Gout Flares : Gout flare prophylaxis is recommended for at least the first 6 months of KRYSTEXXA therapy. ( 5.4 ) Congestive Heart Failure : Congestive heart failure exacerbation may occur. Monitor patients closely following infusion. ( 5.5 ) 5.1 Anaphylaxis In a 52-week controlled trial, which evaluated KRYSTEXXA co-administered with methotrexate compared to KRYSTEXXA alone, subjects were pre-treated with standardized infusion reaction prophylaxis and were discontinued from treatment with KRYSTEXXA if serum uric acid levels increased to above 6 mg/dL at 2 consecutive visits after the initiation of KRYSTEXXA therapy to reduce the risk of anaphylaxis. One subject randomized to the group treated with KRYSTEXXA co-administered with methotrexate (1%) experienced anaphylaxis during the first infusion and no subjects experienced anaphylaxis in the group treated with KRYSTEXXA alone [see Adverse Reactions (6.1) , Clinical Studies (14) ] . During pre-marketing clinical trials with KRYSTEXXA alone, KRYSTEXXA was not discontinued following 2 consecutive serum uric acid levels above 6 mg/dL.

The following serious adverse reactions are discussed in greater detail in other sections of the label: Anaphylaxis [see Warnings and Precautions (5.1) ] Infusion Reactions [see Warnings and Precautions (5.2) ] G6PD Deficiency Associated Hemolysis and Methemoglobinemia [see Warnings and Precautions (5.3) ] Gout Flares [see Warnings and Precautions (5.4) ] Congestive Heart Failure [see Warnings and Precautions (5.5) ] Co-administration with methotrexate: The most common adverse reactions (≥ 5% of patients) are gout flares, arthralgia, COVID-19, nausea and fatigue. ( 6.1 ) KRYSTEXXA alone: The most common adverse reactions (≥ 5% of patients) are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug, and may not predict the rates observed in a broader patient population in clinical practice.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of KRYSTEXXA in pregnant women. Based on animal reproduction studies, no structural abnormalities were observed when pegloticase was administered by subcutaneous injection to pregnant rats and rabbits during the 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 the MRHD, respectively [see Data ]. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinical recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In 2 separate embryo-fetal developmental studies, pregnant rats and rabbits received pegloticase during the period of organogenesis at doses up to approximately 50 and 75 times the MRHD, respectively (on a mg/m 2 basis at maternal doses up to 40 and 30 mg/kg twice weekly, in rats and rabbits, respectively). No evidence of structural abnormalities was observed in rats or rabbits.

Metabolism

Pegloticase levels were determined in serum based on measurements of uricase enzyme activity. Following single intravenous infusions of 0.5 mg to 12 mg pegloticase in 23 patients with symptomatic gout, maximum serum concentrations of pegloticase increased in proportion to the dose administered.

No reports of overdosage with KRYSTEXXA 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.

• Sep 14, 2010BLABLA125293Horizon Pharma

1. 1Gout54616%
2. 2Blood Uric Acid Increased38711%
3. 3Infusion Related Reaction36211%
4. 4Therapeutic Response Decreased2407.0%
5. 5Dyspnoea1684.9%
6. 6Drug Ineffective1484.3%
7. 7Urticaria1394.1%
8. 8Nausea1353.9%
9. 9Pruritus1303.8%
10. 10Rash1273.7%
11. 11Off Label Use1223.6%
12. 12Chest Pain1123.3%
13. 13Pain1073.1%
14. 14Dizziness1063.1%
15. 15Anaphylactic Reaction1002.9%

The 10 most recently updated of 23 ClinicalTrials.gov registrations naming Pegloticase as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Double-blind, Randomized Controlled Trial to Investigate the Efficacy, Safety, and Pharmacokinetics of Pegloticase Administration Via Subcutaneous and Intravenous Routes Both With Methotrexate in Participants With Uncontrolled Gout
  Recruiting · Phase 3 · Interventional · 270 enrolled · Amgen
  NCT07388498updated 2026-06-10
• A Phase 4, Open-label Study of KRYSTEXXA® (Pegloticase) Co-administered With Methotrexate (MTX) in Patients With Uncontrolled Gout (FORWARD OL)
  Completed · Phase 4 · Interventional · 54 enrolled · Amgen
  NCT04762498updated 2026-05-19
• Evaluation of Efficacy and Safety of AR882 and XOI Co-administration in Uricase Treatment Failed Patients
  Active not recruiting · Phase 2 · Interventional · 15 enrolled · Arthrosi Therapeutics
  NCT07116746updated 2026-05-15
• Pegloticase for the Reduction of Uric Acid in Patients With Tumor Lysis Syndrome
  Completed · Phase 4 · Interventional · 10 enrolled · M.D. Anderson Cancer Center
  NCT04745910updated 2026-05-06
• A Trial to Investigate the Non-inferiority of Pegloticase Administered Every 4 Weeks (Q4W) With MTX Compared With Every 2 Weeks (Q2W) With MTX in Participants With Uncontrolled Refractory Gout
  Completed · Phase 4 · Interventional · 262 enrolled · Amgen
  NCT06229145updated 2026-04-09
• Recapturing Immune Tolerance to Pegloticase for the Management of Tophaceous Gout
  Completed · Phase 1 · Interventional · 2 enrolled · University of California, Los Angeles
  NCT06186219updated 2025-11-20
• Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate
  Completed · Phase 4 · Interventional · 191 enrolled · Amgen
  NCT04511702updated 2025-10-20
• Pegloticase and Methotrexate Co-administered in Participants With Uncontrolled Gout Who Previously Failed Pegloticase Monotherapy
  Completed · Phase 4 · Interventional · 11 enrolled · Amgen
  NCT04772313updated 2024-06-27
• Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout
  Completed · Phase 4 · Interventional · 152 enrolled · Amgen
  NCT03994731updated 2024-06-26
• Study of Pegloticase (KRYSTEXXA®) Plus Methotrexate in Patients With Uncontrolled Gout
  Completed · Phase 4 · Interventional · 14 enrolled · Amgen
  NCT03635957updated 2024-06-26

CPIC-curated drug–gene pairs for Pegloticase. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• G6PDCPIC AClinPGx 3FDA label: Testing Required
  G6PD

Frequently asked questions

How does Pegloticase work?

KRYSTEXXA is a uric acid specific enzyme which is a recombinant uricase and achieves its therapeutic effect by catalyzing the oxidation of uric acid to allantoin, thereby lowering serum uric acid. Allantoin is an inert and water-soluble purine metabolite; it is readily eliminated, primarily by renal excretion.

What is Pegloticase used for?

According to FDA labeling, Pegloticase carries indications including: KRYSTEXXA ® (pegloticase) is 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pegloticase?

Pegloticase is classified as Other antigout preparations, Uric Acid-specific Enzyme, Enzyme Activators.

What are the brand names for Pegloticase?

Pegloticase is marketed under brand names including Krystexxa.

What are the contraindications for Pegloticase?

Pegloticase labeling lists contraindications including: KRYSTEXXA is contraindicated in: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency [see Warnings and Precautions (5.3) ]. Patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components.. Always consult the full prescribing information and a clinician.