Prophylaxis during Anti-Hyperuricemic Therapy

• The increase in uric acid excretion early in the course of treatment with uricosuric agents can promote urinary stone or gravel formation.
• urate-lowering disrupts the physical state and/or surface chemical composition of preformed crystal deposits and thus makes the component crystals interactive with local cells competent
• The risk of precipitating urinary stone formation and acute gouty arthritis can be minimized by starting with low doses of antihyperuricemic therapy and by hydration (2 or more L of fluid daily). 
• Alkalinization of the urine is, in most patients, unnecessary

Colchicine

(1) Dosing

• 0.6 mg orally once or twice daily for patients with normal renal function.
• Many patients, particularly older individuals, develop loose or diarrheal stools that preclude use of the recommended colchicine dose.
• Satisfactory prophylaxis in such patients is often attained with the lower colchicine doses of 0.6 mg once daily or even every other day.
• reduced to 0.6 mg per day in patients with a creatinine clearance of 35 to 49 mL/min and to 0.6 mg every two to three days in patients with a creatinine clearance of 10 to 34 mL/min.
• not be used in patients with a creatinine clearance <10 mL/min or in patients undergoing dialysis for end stage renal disease.

(2) Duration

• generally given as short-term therapy (ie, for periods not exceeding six months’ duration)

(3) Concerns

• neuromyopathy is a potential complication of chronic therapy, particularly in patients with a reduced creatinine clearance.
• It should be suspected in patients who complain of paresthesias, numbness, and/or weakness.
• Most cases occur in patients treated with daily low dose colchicine for months to years.
• Patients taking HMG-CoA reductase inhibitors (statins) may be at increased risk for colchicine-induced myopathy

 NSAID

(1) Dosing

• Indomethacin (25 mg twice daily) appears to be effective for prophylaxis in patients who do not tolerate low dose colchicine, although the data are very limited
• NSAIDs other than indomethacin may also be effective and may be associated with a lower frequency of side effects.

(2) Duration

• Because of potential toxicity, the continued use of colchicine or NSAIDs is not recommended after persistent normouricemia has been achieved with antihyperuricemic drugs.
• In patients without evident tophi, prophylaxis can often be safely discontinued six months after normal serum urate values have been obtained.

(3) Concerns

• Gastrointestinal toxicity is a potential complication of all NSAIDs, and these agents should not be used in patients with moderate or more severe renal impairment

 Reference:

1. www.uptodate.com