Pegloticase

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Pegloticase
Names
Trade namesKrystexxa, Puricase
Clinical data
Drug classUrate oxidase[1]
Main usesGout[1]
Side effectsWorsening gout, pain at the site of injection, nausea, bruising, constipation, anaphylaxis[1]
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
use
Intravenous
Typical dose8 mg[1]
External links
AHFS/Drugs.comMonograph
US NLMPegloticase
MedlinePlusa611015
Legal
License data
Legal status
Pharmacokinetics
BioavailabilityN/A
Elimination half-life10–12 days
Chemical and physical data
FormulaC1549H2430N408O448S8 (peptide monomer)
Molar mass497 kg/mol (polymer-modified tetramer) g·mol−1
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Pegloticase, sold under the brand name Krystexxa, is a medication used to treat chronic gout.[1] It is a third line treatment in those in whom other treatments are not tolerated.[2] It is given by injection into a vein.[1]

Common side effects include worsening gout, pain at the site of injection, nausea, bruising, constipation, and anaphylaxis.[1] Other side effects may include worsening heart failure.[1] It should not be used in people with G6PD deficiency.[1] It is a manufactured form of the enzyme urate oxidase (uricase).[1]

Pegloticase was approved for medical use in the United States in 2010.[1] It was approved in 2013 in Europe but this was withdrawn in 2016.[3] In the United States it costs about 26,000 USD per dose.[4]

Medical uses

It is an option for the 3% of people with gout who are intolerant to other medications.[5] Pegloticase is given as an intravenous infusion every two weeks,[5] and has been found to reduce uric acid levels in this population.[6] 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.[7] About 40% of people develop resistance to the medication over time.[2]

Dosage

It is used at a dose of 8 mg every two to four weeks.[1]

Side effects

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.[8]

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.[9]

Chemistry

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).[10]

History

It was developed by Savient Pharmaceuticals.[10][11]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 "Pegloticase Monograph for Professionals". Drugs.com. Retrieved 27 October 2021.
  2. 2.0 2.1 Dalbeth, N; Merriman, TR; Stamp, LK (22 October 2016). "Gout". Lancet. 388 (10055): 2039–2052. doi:10.1016/s0140-6736(16)00346-9. PMID 27112094. S2CID 208790780.
  3. "Krystexxa Withdrawal of the marketing authorisation in the European Union" (PDF). Retrieved 25 March 2017.
  4. "Krystexxa Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 27 October 2021.
  5. 5.0 5.1 "FDA approves new drug for gout". FDA. September 14, 2010.
  6. Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vázquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW, Hamburger SA, Becker MA (Aug 17, 2011). "Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials". JAMA: The Journal of the American Medical Association. 306 (7): 711–20. doi:10.1001/jama.2011.1169. PMID 21846852.
  7. Sriranganathan, Melonie K.; Vinik, Ophir; Pardo Pardo, Jordi; Bombardier, Claire; Edwards, Christopher J. (2021-08-11). "Interventions for tophi in gout". The Cochrane Database of Systematic Reviews. 8: CD010069. doi:10.1002/14651858.CD010069.pub3. ISSN 1469-493X. PMC 8406833. PMID 34379791.
  8. Abraham J. Domb, Neeraj Kumar (2 August 2011). Biodegradable Polymers in Clinical Use and Clinical Development. John Wiley & Sons. ISBN 9781118015803.
  9. Biggers, K; Scheinfeldt, N (2008). "Pegloticase, a polyethylene glycol conjugate of uricase for the potential intravenous treatment of gout". Current Opinion in Investigational Drugs. 9 (4): 422–429. PMID 18393109.
  10. 10.0 10.1 "Statement on a nonproprietary name adopted by the USAN Council" (PDF).
  11. "Savient Pharmaceuticals: Uricase". Archived from the original on 2006-07-10. Retrieved 2009-03-29.

External links

Identifiers: