|Trade names||Krystexxa, Puricase|
|Drug class||Urate oxidase|
|Side effects||Worsening gout, pain at the site of injection, nausea, bruising, constipation, anaphylaxis|
|Typical dose||8 mg|
|Elimination half-life||10–12 days|
|Chemical and physical data|
|Formula||C1549H2430N408O448S8 (peptide monomer)|
|Molar mass||497 kg/mol (polymer-modified tetramer) g·mol−1|
Pegloticase, sold under the brand name Krystexxa, is a medication used to treat chronic gout. It is a third line treatment in those in whom other treatments are not tolerated. It is given by injection into a vein.
Common side effects include worsening gout, pain at the site of injection, nausea, bruising, constipation, and anaphylaxis. Other side effects may include worsening heart failure. It should not be used in people with G6PD deficiency. It is a manufactured form of the enzyme urate oxidase (uricase).
Pegloticase was approved for medical use in the United States in 2010. It was approved in 2013 in Europe but this was withdrawn in 2016. In the United States it costs about 26,000 USD per dose.
It is an option for the 3% of people with gout who are intolerant to other medications. Pegloticase is given as an intravenous infusion every two weeks, and has been found to reduce uric acid levels in this population. There is moderate quality evidence that It is useful for tophi but has a high rate of side effects and withdrawals due to adverse events. About 40% of people develop resistance to the medication over time.
It is used at a dose of 8 mg every two to four weeks.
In individuals with glucose-6-phosphate dehydrogenase deficiency, pegloticase may precipitate a severe, life-threatening hemolysis with methemoglobinemia; it is therefore contraindicated in such individuals. Pegloticase may also show immunogenicity.
Mechanism of action
Pegloticase is a recombinant porcine-like uricase. Similarly to rasburicase, it metabolises uric acid to allantoin. This reduces the risk of precipitates, since allantoin is five to ten times more soluble than uric acid.
In contrast to rasburicase, pegloticase is pegylated to increase its elimination half-life from about eight hours to ten or twelve days, and to decrease the immunogenicity of the foreign uricase protein. This modification allows for a dosing interval of two to four weeks, increasing its suitability for long-term treatment.
Pegloticase is a tetrameric protein composed of four identical chains of about 300 amino acids each. Approximately nine of the 30 lysine residues in each chain are pegylated. These PEG chains consist of about 225 ethylene glycol units each (10 kg/mol PEG).
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