Hyperuricemia Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Pharmacotherapy for hyperuricemia is based on whether patients are overproducers or undersecretors. Allopurinol continues to be the mainstay for the treatment of patients who are overproducers, although the drug febuxostat is being investigated as a possible replacement for allopurinol. Febuxostat is a nonpurine selective xanthine oxidase inhibitor for the treatment of gout.^[6]

A 52-week randomized study published in 2005 evaluated over 700 patients with gout and serum uric acid levels of at least 8 mg/dL. More than 50% of patients taking 80 mg/d of febuxostat achieved a serum uric acid level of less than 6 mg/dL at the last 3 monthly measurements, according to the study. This was in comparison to 62% of patients who reached this primary endpoint with 120 mg/d of febuxostat and 21% of patients who achieved this target with 300 mg/d of allopurinol.

However, follow-up comments by the author acknowledged that discontinuation of the drug occurred 2 times as often in the low-dose febuxostat group and 3 times as often in the high-dose febuxostat group, as it did in the allopurinol group. Moreover, the occurrence of 4 deaths in the febuxostat groups, as compared with none in the allopurinol group, is a concern, and therefore, febuxostat needs further study.^{[6, 7, 8]} Febuxostat was approved by the US Food and Drug Administration (FDA) in February 2009 for long-term treatment of hyperuricemia in gout.

Rasburicase is another medication that was introduced to control hyperuricemia. It is a recombinant urate oxidase that is indicated for preventing complications of hyperuricemia during the tumor lysis syndrome. Since losartan has been found to have an uricosuric property, it may be worthwhile to use it in hypertensive patients with hyperuricemia that lack any contraindication to angiotensin receptor blockers. Other uricosuric drugs used in underexcretors are mentioned below.

Class Summary

Management of pain and inflammation in gout. Have analgesic, anti-inflammatory, and antipyretic properties. Inhibit the enzyme cyclooxygenase, thus inhibiting biosynthesis of prostaglandins and thromboxanes from arachidonic acid.

Indomethacin (Indochron E-R, Indocin)

Rapidly absorbed. Metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.

Discontinue 3-4 d following symptom resolution.

Class Summary

Prevent gouty arthritis attacks and nephropathy. Used to treat hyperuricemia secondary to diuretics or antineoplastics. Prevent recurrent uric acid nephrolithiasis.

Allopurinol (Zyloprim)

Inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine. Reduces synthesis of uric acid without disrupting biosynthesis of vital purines.

Febuxostat (Uloric)

Xanthine oxidase inhibitor. Prevents uric acid production and lowers elevated serum uric acid levels. Indicated for long-term management of hyperuricemia associated with gout.

Class Summary

Competitively inhibit reabsorption of uric acid in proximal renal tubule. This promotes excretion of uric acid and lowers serum uric acid levels.

Probenecid (Benemid)

Used to treat and prevent hyperuricemia associated with gout and gouty arthritis.

Class Summary

Treatment of gouty arthritis attacks and prevention of their recurrence. Used in management of familial Mediterranean fever.

Colchicine

Reduces formation of uric acid crystals in affected joint, thereby reducing amount of acute inflammation and pain; also decreases uric acid levels in blood. Can be used in combination with probenecid on long-term to prevent gout or can be used alone to treat pain and inflammation of acute gout attacks. Discontinue when pain of gout attack begins to subside, when maximum dose is reached, or when GI symptoms (eg, nausea, vomiting, diarrhea) indicate cellular poisoning. Decreases leukocyte motility and phagocytosis in inflammatory responses.

Class Summary

Decrease solubility of uric acid. Adequate hydration recommended to maintain high urine output.

Acetazolamide (Diamox, Diamox sequels)

Used to further enhance uric acid elimination.

Class Summary

Have both anti-inflammatory (glucocorticoid) and salt retaining (mineralocorticoid) properties. Glucocorticoids have profound and varied metabolic effects and modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Orasone, Meticorten)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dexamethasone (Decadron, AK-Dex, Alba-Dex)

Decreases inflammation by suppressing migration of PMN leukocytes and reducing capillary permeability.

Class Summary

These agents facilitate conversion of urate to a more soluble product, allantoin.

Pegloticase (Krystexxa)

Pegylated uric acid–specific enzyme, which is a polyethylene glycol conjugate of recombinant uricase. Achieves its therapeutic effect by catalyzing oxidation of uric acid to allantoin, thereby lowering serum uric acid levels. Indicated for gout in adults refractory to conventional therapy (ie, serum uric acid levels have failed to normalize and signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at maximum appropriate dose or xanthine oxidase inhibitors are contraindicated).

Rasburicase (Elitek)

A recombinant form (derived from Saccharomyces cerevisiae -synthesized, Aspergillus flavus) of the enzyme urate oxidase, which oxidizes uric acid to allantoin. Indicated for treatment and prophylaxis of severe hyperuricemia associated with the treatment of malignancy. Hyperuricemia causes a precipitant in the kidneys, which leads to acute renal failure. Unlike uric acid, allantoin is soluble and easily excreted by the kidneys. Elimination half-life is 18 h.

Class Summary

These agents are used to raise the pH in the urine.

Potassium citrate (Citra K, Polycitra K)

Pleasant-tasting oral systemic alkalizer containing potassium citrate and citric acid in a sugar-free base.

Each unit dose packet contains potassium citrate monohydrate 3300 mg and citric acid monohydrate 1002 mg. Each unit dose packet, when reconstituted, supplies the same amount of active ingredients as is contained in 15 mL (1 tablespoonful) Polycitra-K oral solution and provides 30 mEq potassium ion and is equivalent to 30 mEq bicarbonate.

Absorbed and metabolized to potassium bicarbonate, thus acting as a systemic alkalizer. Effects are essentially those of chlorides before absorption and those of bicarbonates subsequently. Oxidation is virtually complete so that < 5% of the potassium citrate is excreted in the urine unchanged.

Highly concentrated and, when administered after meals and before bedtime, allows one to maintain an alkaline urinary pH at all times, usually without necessity of 2 am dose. Alkalinizes urine without producing systemic alkalosis in recommended dosage.