Nonsteroidal Anti-inflammatory Drugs
NSAIDs are the drugs of choice in most patients with acute gout who do not have underlying health problems. However, aspirin should not be used because it can alter uric acid levels and potentially prolong and intensify an acute attack.
Avoid NSAIDs in patients who have a history of peptic ulcer disease or GI bleeding, patients with renal insufficiency, patients with abnormal hepatic function, patients taking warfarin (selective COX-2 inhibitors can be used but used cautiously), and patients in the intensive care unit who are predisposed to gastritis. In patients with diabetes and those who are receiving concomitant angiotensin-converting enzyme (ACE) inhibitors.
NSAIDs are prescribed at full dosage for 2-5 days to control the acute attack, and the dose is reduced to approximately one half to one fourth of that amount once the acute attack is controlled. Taper the dose down over approximately 2 weeks. But the consistent low-dose of NSAIDs used for 6-24 months may help to prevent the occurring of acute gout attack during the chronic lowering uric acid treatment.
Gout symptoms should be absent for at least 2 days before the NSAID is discontinued.
Although colchicine was once the treatment of choice for acute gout, it is now a second-line approach because of its narrow therapeutic window and risk of toxicity.
Colchicine therapy must be initiated within 24 hours of onset of the acute attack to be effective. Dosing recommendation for colchicine in acute gout therapy have been modified in recent years because of an increased awareness of its toxicities. The most recent recommendations have been trending toward lowered daily and cumulative doses. The favored regimen is low-dose colchicine 1.8 mg total over 1 hour (1.2 mg PO initially then 0.6 mg q1hr, total not to exceed 1.8 mg over 1 hour-period).
Colchicine should not be used if the glomerular filtration rate (GFR) is less than 10 mL/min, and the dose should be decreased by at least half if the GFR is less than 50 mL/min. Colchicine should also be avoided in patients with hepatic dysfunction, biliary obstruction, or an inability to tolerate diarrhea.
For prophylaxis the dose of colchicine is 0.6 mg bid or lower. In patients with renal insufficiency, this dose may need to be decreased to daily or overy-other-day administration. Even in prophylactic dose, colchicines can cause marrow toxicity and neuromyopathy in the setting of renal insufficiency. Long-term use of colchicine can lead to a muscle weakness associated with elevated levels of creatine kinase due to a drug-induced neuromyopathy, particularly in patients with renal insufficiency.
Corticosteroids can be given to patients with gout who cannot use NSAIDs or coclchicine, but adrenocorticotropic hormone (ACTH) would be preferred. Steroids can be given orally, intravenously, intramuscularly, intra-articularly, or indirectly via ACTH.
ACTH 40 IU can be given to induce corticosteroid production by the patient’s own adrenal glands. Such a regimen dose not depend on the patient to properly taper prednisone. Using parenteral corticosteroids confers no advantage unless the patient cannot take oral medications.
Intra-articular, long-acting (depot) corticosteroids are particularly useful in patients with a monoarticular flare to help reduce the systemic effects of oral steroids.
Allopurinol blocks xanthine oxidase and thus reduces the generation of uric acid. Therefore, it should be used in patients who overproduce uric acid. It is the most effective urate-lowering agent. However, alcohol can interfere with effectiveness of allopurinol.
Approximately 3-10% of patients taking allopurinol develop dyspepsia, headache, diarrhea, and/or pruritic maculopapular rash. Less frequently, patients taking allopurinol can develop allopurinol hypersensitivity, which carries a mortality rate of 20-30%. Features of allopurinol hypersensitivity include fever, toxic epidermal necrolysis, bone marrow suppression, eosinophilia, leukocytosis, renal failure, hepatic failure, and vasculitis. Corticosteroids are often used to treat allopurinol hypersensitivity.
Allopurinol hypersensitivity is more likely to occur in patients with renal insufficiency, patients who are taking a diuretic, and patients begun on 300 mg of allopurinol. Although allopurinol hypersensitivity is more common (although still rare) in patients with renal insufficiency, this effect dose not appear to be dose-related. Thus, a slow and careful titration of allopurinol dosing sufficient to achieve uric acid levels of less than 6 mg/dL is also recommended in these patients.
Allopurinol is also associated with the drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. DRESS syndrome affects the liver, kidney, and skin. It is a delayed-hypersensitivity response occurring 6-8 weeks after beginning allopurinol. The underlying mechanism is thought to be a cell-mediated immunity to allopurinol and its metabolites. Although occurrence is 0.4%, the rate of organ failure and death is high. Treatment is with intravenous N-acetyl cysteine and steroids. Allopurinol should be discontinued in patients who develop a rash.
In most patients, start at 100 mg per day (50 mg in patients with renal insufficiency) and adjust the dose monthly according to the uric acid level until the goal of a uric acid level of 6 mg/dL or less is achieved.
While adjusting the dosage of allopurinol in patients who are being treated with colchicine and/or anti-inflammatory agents, it is wise to continue the latter therapy until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months.
Update from Medscape Reference at http://emedicine.medscape.com/article/329958-medication#6 on Sep 6th 2013.
Pegloticase is a pegylated uric acid–specific enzyme that is a polyethylene glycol conjugate of recombinant uricase. It achieves its therapeutic effect by catalyzing oxidation of uric acid to allantoin, thereby lowering serum uric acid levels. Pegloticase is indicated for gout in adults refractory to conventional therapy (ie, when serum uric acid levels have not normalized and either signs and symptoms are inadequately controlled with xanthine oxidase inhibitors or uricosurics at maximum appropriate doses or xanthine oxidase inhibitors are contraindicated).
The dosage is 8 mg IV every 2 weeks. Complications include anaphylaxis, infusion reactions, flare of gout attacks in 63-86% of patients and nephrolithiasis in 13-14%, along with arthralgias, nausea, dyspepsia, muscle spasms, pyrexia, back pain, diarrhea, and rash.[134, 135] Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a contraindication.