KRYSTEXXA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KRYSTEXXA (KRYSTEXXA).
KRYSTEXXA (pegloticase) is a recombinant uricase enzyme conjugated to polyethylene glycol (PEG) that catalyzes the oxidation of uric acid to allantoin, thereby lowering serum uric acid levels. Allantoin is a more water-soluble metabolite that is readily excreted by the kidneys.
| Metabolism | Pegloticase is a PEGylated uricase; it is not metabolized by cytochrome P450 enzymes. The drug is degraded via proteolysis into small peptides and amino acids. |
| Excretion | Renal: negligible (<1% unchanged); metabolism via proteolysis to small peptides and amino acids; no biliary/fecal elimination quantified. |
| Half-life | Terminal half-life: 10–15 days in patients with chronic gout; prolonged due to immunogenicity and target-mediated drug disposition. |
| Protein binding | Not applicable (pegylated recombinant uricase; no significant binding to plasma proteins). |
| Volume of Distribution | Vd ~3–4 L (restricted to intravascular space; no extensive tissue distribution). |
| Bioavailability | IV only; 100% bioavailability by intravenous route. |
| Onset of Action | IV: Clinical response (serum urate reduction) observed within 24–48 hours after first infusion. |
| Duration of Action | Serum urate suppression persists for 2–4 weeks post-infusion; repeated dosing every 2 weeks required for sustained effect. |
8 mg intravenously every 2 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended for renal impairment, but caution in severe renal impairment (GFR <30 mL/min) due to limited data. |
| Liver impairment | No dose adjustment recommended for hepatic impairment; limited data in Child-Pugh class C. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; limited data in patients >65 years, but no age-related differences observed in clinical studies. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KRYSTEXXA (KRYSTEXXA).
| Breastfeeding | No human data on pegloticase excretion in breast milk. Due to high molecular weight, excretion is likely low, but unknown. M/P ratio not determined. Caution advised, weigh benefits against potential infant exposure. |
| Teratogenic Risk | Pregnancy Category C. No adequate studies in pregnant women. In animal studies, pegloticase caused embryotoxicity and skeletal abnormalities at doses 2-4 times the human dose. Risk cannot be ruled out; use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Anaphylaxis and infusion reactions have been reported. KRYSTEXXA should be administered in a healthcare setting prepared to manage anaphylaxis. Patients should be premedicated with antihistamines and corticosteroids. Discontinue infusion if anaphylaxis occurs.
| Serious Effects |
["Glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolysis and methemoglobinemia"]
| Precautions | ["Anaphylaxis and infusion reactions: Risk is highest in patients with loss of urate-lowering efficacy. Premedicate and monitor closely.","Congestive heart failure exacerbation: Use caution in patients with CHF.","Gout flare: May increase after initiation; treat prophylactically."] |
Loading safety data…
| Monitor for infusion reactions, anaphylaxis, and gout flares. In pregnancy, monitor fetal growth and well-being via ultrasound if exposure occurs. Assess maternal blood pressure and renal function. |
| Fertility Effects | Animal studies show no effect on male or female fertility at clinically relevant doses. No human data available. Potential impact on reproduction is not established. |