Lesinurad: a novel therapeutic option in the pharmacotherapy of gout

Authors

  • Damal Kandadai Sriram Department of Endocrinology and Diabetology, Hindu Mission Hospital, West Tambaram, Chennai 600045, Tamilnadu, India
  • Surendran Venkatesan Department of Clinical Research, Hindu Mission Hospital, West Tambaram, Chennai 600045, Tamilnadu, India
  • Melvin George Department of Clinical Research, Hindu Mission Hospital, West Tambaram, Chennai 600045, Tamilnadu, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20164783

Keywords:

Allopurinol, Gout, Hyperuricemia, Lesinurad, Renal function

Abstract

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Current therapies for chronic gout include mainly allopurinol and febuxostat. Inspite of the availability of these medications for several years, a significant number of patients do not have adequate control of uric acid levels resulting in acute gout flares. Lesinurad is the most recent drug molecule approved by US FDA & EMA for the treatment of gout in patients with uncontrolled gout along with allopurinol. Lesinurad prevents reabsorption of uric acid from the renal tubules, resulting in uricosuria. The efficacy of the lesinurad was demonstrated in three randomized phase 3 controlled clinical trials where the drug was primarily evaluated in the setting of background therapy with allopurinol or febuxostat. There is a definite risk of nephrotoxicity with monotherapy and when the drug is used in patients who have inadequate renal function. The drug does appear to be relatively safe, though the inconclusive cardiovascular safety of the drug has prompted the regulatory agency to mandate post marketing trials to evaluate the safety of this molecule. Nevertheless, lesinurad does appear to have a lot of promise as a front line drug molecule in the control of hyperuricemia.

References

Hainer BL, Matheson E, Wilkes RT. Diagnosis, treatment, and prevention of gout. Am Fam Physician. 2014 Dec 15;90(12):831-6.

Singh JA. Emerging therapies for gout. Expert Opin Emerg Drugs. 2012 Dec;17(4):511-8.

Gustafsson D, Unwin R. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013;14:164.

Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004 Mar 11;350(11):1093-103.

Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet Lond Engl. 2004 Apr 17;363(9417):1277-81.

Finch A, Kubler P. The management of gout. Aust Prescr. 2016;39:119-22.

Shen Z, Rowlings C, Kerr B, Hingorani V, Manhard K, Quart B, et al. Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males. Drug Des Devel Ther. 2015;9:3423-34.

Saag KG, Fitz-Patrick D, Kopicko J, Fung M, Bhakta N, Adler S, et al. Lesinurad Combined With Allopurinol: Randomized, Double-Blind, Placebo-Controlled Study in Gout Subjects With Inadequate Response to Standard of Care Allopurinol (A US-based Study). Arthritis Rheumatol. 2016 Aug 26.

Lesinurad in Combination With a Xanthine Oxidase Inhibitor for Treatment of Hyperuricemia Associated With Gout. Briefing Document for the Arthritis Advisory Committee. Available from http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM467951.pdf.

SAT0307 Lesinurad Monotherapy in Gout Patients Intolerant to Xanthine Oxidase Inhibitors (Light) A Randomized, Double-Blind, Placebo-Controlled, 6-Month Phase III Clinical Trial.htm.

Hoy SM. Lesinurad -First global approval. Drugs. 2016;76:509-16.

Fleischmann R, Kerr B, Yeh LT, Suster M, Shen Z, Polvent E, et al. Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia. Rheumatology. 2014 Dec 1;53(12):2167-74.

FDA Approves Zurampic for Patients With Gout [Internet]. Medscape. [cited 2016 May 18]. Available from: http://www.medscape.com/viewarticle/856374

UCM467951.pdf. [cited 2016 May 31]. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM467951.pdf

Downloads

Published

2016-12-24

How to Cite

Sriram, D. K., Venkatesan, S., & George, M. (2016). Lesinurad: a novel therapeutic option in the pharmacotherapy of gout. International Journal of Basic & Clinical Pharmacology, 6(1), 214–216. https://doi.org/10.18203/2319-2003.ijbcp20164783

Issue

Section

New Drug Update