Urate Lowering Therapies

Uricosuric Agents (e.g. probenecid) Allopurinol

Indication/Use

  • Urate lowering
  • Hyperuricemia, not indicated for patients with gout who overproduce uric acid
  • Used in patients with intolerance to or contraindication for allopurinol
  • Reduces the production of uric acid by blocking xanthine oxidase
  • Urate lowering

Advantages

  • Treat most common etiology-uric acid under-excretion
  • Generic
  • Once-a-day dosing
  • Effective for both uric acid over-producers and underexcretors
  • Generic

Limitations

  • Rebound gout flares
  • Risk of nephrolithiasis and urolithiasis
  • Ineffective in renal insufficiency (<60 ml/min)
  • Poorly tolerated flushing,rash, GI intolerance, urate stone formation
  • Multiple daily dosing
  • Drug interactions (salicylates, NSAIDs, penicillin, warfarin, sulfonylureas, insulin, methotrexate)
  • Rebound gout flares
  • Non-selective enzyme inhibition
  • Intolerance in 10-15% of patients
  • Potentially fatal hypersensitivity syndrome
  • Dosing by renal function
  • Common AEs include rash and GI intolerance
  • Drug interactions (azathioprine, warfarin, ampicillin, thiazide diuretics, chlorpropamide, cyclosporine, uricosuric agents)

References: Becker & Ruoff 2010, Zhang et al. 2010 (Eular Part II); Schumacher & Chen 2008