Recombinant Uricase — Urate-Lowering Biologic Pregnancy: There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies no structural abnormalities were observed in rats and rabbits dosed during organogenesis at up to 50 and 75 times the maximum recommended human dose, but decreases in mean fetal and pup body weights were observed at those exposures.

Pegloticase (Recombinant PEGylated Uricase — Refractory Gout)

Brand names: Krystexxa

Pegloticase is a specialist intravenous recombinant PEGylated uricase used in the treatment of severe, debilitating chronic refractory gout in adults whose disease has not responded to conventional urate-lowering therapy.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 8 mg

Route: Intravenous infusion over a period of no less than 120 minutes. Do NOT administer as an intravenous push or bolus. Ready-to-Use vial 8 mg/50 mL (0.16 mg/mL) is infused using an infusion pump; the To-be-Diluted vial 8 mg/mL requires 1 mL to be withdrawn and injected into a single 250 mL bag of 0.9% or 0.45% sodium chloride injection (gravity feed, syringe-type pump or infusion pump may be used). Do not mix or dilute with other drugs. Flush the line with sodium chloride after the Ready-to-Use vial to ensure the full dose is delivered.

Frequency: Every two weeks

Co-administered with weekly oral methotrexate 15 mg together with folic acid or folinic acid supplementation; pegloticase alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate. If co-administering, start weekly methotrexate and folic/folinic acid supplementation at least 4 weeks before initiating pegloticase and continue throughout treatment. BEFORE STARTING: discontinue oral urate-lowering medications and do not institute oral urate-lowering therapy while the patient is on pegloticase. MONITORING: measure serum uric acid before each infusion and discontinue treatment if levels increase above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed — the risk of infusion reactions including anaphylaxis is higher in patients who have lost therapeutic response. INFUSION REACTION PRECAUTIONS: administer in a healthcare setting by providers prepared to manage infusion reactions including anaphylaxis; pre-medicate with antihistamines and corticosteroids; if an infusion reaction occurs the infusion may be slowed, or stopped and restarted at a slower rate, at the physician's discretion; because reactions can occur after completion, observation for approximately an hour post-infusion should be considered. GOUT FLARES: flare prophylaxis is recommended for at least the first 6 months of therapy. The optimal treatment duration has not been established. ELDERLY: no dose adjustment is needed for patients 65 years of age and older. PAEDIATRIC: safety and effectiveness in patients under 18 years of age have not been established — no paediatric dose is stated in the source. SOURCE: no UK SPC (eMC) record was present in this bundle — the dose above is from the US prescribing information for KRYSTEXXA (Horizon Therapeutics USA, label date 2026-07-09, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57c98104-8dbe-4e55-9cb6-7b101706b053) and must be verified against UK labelling before publication.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Glucose-6-phosphate dehydrogenase (G6PD) deficiency — screen patients at risk before treatment
History of serious hypersensitivity reactions, including anaphylaxis, to pegloticase or any of its components

Side effects

Gout flares (most common with both regimens)
Infusion reactions and anaphylaxis (anaphylaxis may occur with any infusion)
Nausea and vomiting; arthralgia and fatigue (most common when co-administered with methotrexate, together with COVID-19)
Contusion or ecchymosis, nasopharyngitis, constipation and chest pain (most common when given alone)
G6PD deficiency-associated haemolysis and methaemoglobinaemia; congestive heart failure exacerbation may occur — monitor patients closely following infusion

Interactions

Methotrexate — co-administration of oral methotrexate 15 mg weekly with pegloticase may increase pegloticase concentration compared with pegloticase alone (this combination is the labelled regimen)
Other PEGylated products — anti-pegloticase antibodies appear to bind the PEG portion of the drug, so there may be potential for binding with other PEGylated products; the impact of anti-PEG antibodies on responses to other PEG-containing therapeutics is unknown

Clinical monograph

How it works

It is a pegylated recombinant uricase enzyme that catalyses the oxidation of uric acid to allantoin, a more soluble and readily excreted compound, thereby rapidly lowering serum urate.

Prescribing in practice

Anaphylaxis and infusion reactions can occur, so it must be given under specialist supervision with premedication and resuscitation facilities, and discontinued if serum urate rises persistently as this signals loss of response and increased reaction risk.
It is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficiency owing to the risk of haemolysis and methaemoglobinaemia, so screen high-risk patients beforehand.
Gout flares are common when treatment begins, so anti-inflammatory flare prophylaxis is recommended.

Monitoring

Monitor serum urate before each infusion to detect loss of response and observe closely for infusion and hypersensitivity reactions.

Counselling the patient

You may experience a gout flare early in treatment; this does not mean the medicine is not working.
Report any rash, swelling, chest tightness or breathlessness during or after the infusion immediately.

Evidence & guidelines

Use is supported by the Summary of Product Characteristics and randomised controlled trials in chronic refractory gout.

Reference: Sundy et al. NEJM 2011 (CRYSTAL trial); Botson et al. ACR 2023 (MIRROR trial); FDA Krystexxa PI; BSR Gout Guidelines 2022; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways