Gout Treatment / Elevated uric acid levels

allopurinol (Zyloprim ®):

Indications: uric acid stones, tophaceous gout, frequent attacks, >3mg/dl over upper limits of normal uric acid level, underexcretor or overproducer. Doses >300 mg should be given in divided doses.
Allopurinol is used to lower serum and urinary uric acid concentrations in the management of primary and secondary gout. The drug is indicated in patients with frequent disabling attacks of gout. Because therapy with allopurinol is not without some serious risks, the drug is not recommended for the management of asymptomatic hyperuricemia. However, some clinicians have suggested that therapy should be initiated when serum urate concentrations exceed 9 mg/dL because these concentrations are often associated with increased joint changes and renal complications.

Allopurinol may increase the frequency of acute attacks during the first 6-12 months of therapy, even when normal or subnormal serum urate concentrations have been maintained. Therefore, prophylactic doses of colchicine should generally be administered concurrently during the first 3-6 months of allopurinol therapy.

Gout: initially 100mg qd. Increase by 100mg/day q7days, titrate to desired uric acid level (<6 mg/dl). Usual range: (Mild gout): 200-300mg/day. Moderate-severe: 400-600mg/day. (Serum urate concentrations are often reduced more slowly with allopurinol than with uricosuric drugs and minimum concentrations may not be reached for 1-3 weeks. After serum urate concentrations are controlled, it may be possible to reduce dosage; the average adult maintenance dosage is 300 mg daily and the minimum effective dosage is 100-200 mg daily. Allopurinol therapy should be continued indefinitely)

Secondary hyperuricemia associated with chemotherapy:
Oral: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy
I.V.: 200-400 mg/m2/day (maximum: 600 mg/day)
Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.

Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses

Maximum dose/day: 800mg

Renal Dosing:
[>50 ml/min]: No changes
[20-50]: 100-300mg q24h.
[10-20]: 100-200mg q24h.
[<10]: 100mg q24-48h.
[Hemodialysis]: 100mg q24-48h (give dose after dialysis on dialysis days.).

colchicine:

Gouty arthritis:
Prophylaxis of acute attacks: Oral: 0.6 mg twice daily; initial and/or subsequent dosage may be decreased (ie, 0.6 mg once daily) in patients at risk of toxicity or in those who are intolerant (including weakness, loose stools, or diarrhea); range: 0.6 mg every other day to 0.6 mg 3 times/day

Acute attacks:
Oral: Initial: 0.6-1.2 mg, followed by 0.6 every 1-2 hours; some clinicians recommend a maximum of 3 doses; more aggressive approaches have recommended a maximum dose of up to 6 mg. Wait at least 3 days before initiating another course of therapy.
I.V.: Initial: 1-2 mg, then 0.5 mg every 6 hours until response, not to exceed total dose of 4 mg. If pain recurs, it may be necessary to administer additional daily doses. The amount of colchicine administered intravenously in an acute treatment period (generally ~1 week) should not exceed a total dose of 4 mg. Do not administer more colchicine by any route for at least 7 days after a full course of I.V. therapy.

Note (IV): Many experts would avoid use because of potential for serious, life-threatening complications. Should not be administered to patients with renal insufficiency, hepatobiliary obstruction, patients >70 years of age, or recent oral colchicine use. Should be reserved for hospitalized patients who are under the care of a physician experienced in the use of intravenous colchicine.

Surgery: Gouty arthritis, prophylaxis of recurrent attacks: Oral: 0.6 mg/day or every other day; patients who are to undergo surgical procedures may receive 0.6 mg 3 times/day for 3 days before and 3 days after surgery

Primary biliary cirrhosis (unlabeled use): Oral: 0.6 mg twice daily

probenecid (Benemid ®):

Gout: 250 mg orally twice daily x 7 days, then 500mg twice daily.

Rasburicase (Elitek®):

Indicated for the initial management of plasma uric acid levels in pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid.
Recommended dose: 0.15 or 0.20 mg/kg as a single daily dose for 5 days. Because the safety and effectiveness of other schedules have not been established, dosing beyond 5 days or administration of more than one course is not recommended. Chemotherapy should be initiated 4 to 24 hours after the first dose of rasburicase. Rasburicase should be administered as an intravenous infusion over 30 minutes (NEVER as a bolus infusion).

Rasburicase is contraindicated in individuals deficient in glucose-6-phosphate dehydrogenase (G6PD).

sulfinpyrazone (Anturane ®)

Uricosuric agent.
Gout: Initially: 100-200mg orally twice daily with meals. Maintenance: 200mg orally twice daily with meals. Maximum daily dose: 800mg.
Renal Dosing
Do not use if crcl<50 ml/min.

Principles of treatment:

Do not treat asymptomatic hyperuricemia. Also, do not treat hyperuricemia during acute gouty arthritis attack. Treat patients with tophi or polyarticular gout. Probably treat patients with recurrent attacks and serum uric acid >9 mg/dl--Start with low dose and gradually increase (titrate to serum uric acid) over weeks to months. Monitor serum uric acid and aim for uric acid <6.0 mg/dl (or <5.0 with tophi). Use concomitant colchicine prophylaxis until uric acid has been at desired level for some months and no recent gouty attacks have occurred (6-12 months). Use uricosuric drugs (probenecid, sulfinpyrazone) when possible because of low toxicity. Use allopurinol in patients with renal calculi, renal insufficiency, concomitant diuretic therapy, cyclosporine therapy, urate overproduction.

Things to Remember
1. Uric acid may be low, normal, or high during an attack.
2. Low dose colchicine should be started when initiating uric acid lowering drugs.
3. Do not initiate uric acid altering drugs during an acute attack. Wait until attack fully resolved.
4. Indications for Allopurinol use (stated above)
5. Place patient on a low purine diet (seafood, organ meats, spinach, asparagus), alcohol abstinence, weight loss if obese.

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David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.

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