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 (by the colorimetric method) because these concentrations are often associated with increased joint changes and renal complications. Allopurinol is used for the management of gout when uricosurics cannot be used because of adverse effects, allergy, or inadequate response; when there are visible tophi or radiographic evidence of uric acid deposits and stones; or when serum urate concentrations are greater than 8.5-9 mg/dL and a family history of tophi and low urate excretion exists. Allopurinol also is used for the management of primary or secondary gouty nephropathy with or without secondary oliguria. The goal of therapy is to lower serum urate concentration to about 6 mg/dL. Allopurinol will often promote resolution of tophi and uric acid crystals by decreasing serum urate concentrations.
Since allopurinol has no analgesic or anti-inflammatory activity, it is of no value in the treatment of acute gout attacks and will prolong and exacerbate inflammation during the acute phase. 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. Acute attacks may occur in spite of such therapy, but usually become less severe and are of briefer duration after several months of allopurinol therapy. During these acute attacks, allopurinol should be continued without changing dosage and full therapeutic doses of colchicine or other anti-inflammatory agents should be administered.
In early uncomplicated gout, either allopurinol or a uricosuric agent may be used. Since uricosuric agents tend to increase urinary uric acid concentrations and the risk of stone formation, allopurinol is preferred in patients with urinary uric acid excretion of greater than 900 mg daily or with gouty nephropathy, urinary tract stones or obstruction, or azotemia. The activity of allopurinol and uricosurics is additive and, when administered concomitantly, smaller doses of each drug can be used. Combined use of the two types of drugs is especially effective in the presence of tophaceous deposits.
Allopurinol and allopurinol sodium are used for the management of patients with leukemia, lymphoma, and solid tumor malignancies who are undergoing chemotherapy expected to result in tumor lysis and subsequent elevations of serum and urinary uric acid concentrations. For patients unable to tolerate oral therapy, allopurinol sodium for injection may be used. Allopurinol is especially useful in preventing hyperuricemia and uric acid nephropathy resulting from tissue breakdown after cancer chemotherapy or radiation therapy. Allopurinol therapy should be discontinued when the potential for hyperuricemia is no longer present.
In one compassionate treatment program in patients undergoing chemotherapy for the management of malignancies, administration of IV allopurinol sodium was shown to reduce serum uric acid concentrations in 93% of patients with hyperuricemia (68% of whom achieved normal serum urate concentrations) and to maintain normal serum uric acid concentrations in 97% of those patients in whom the drug was initiated while having normal serum urate concentrations. However, because of study design, clinical outcome associated with IV allopurinol sodium therapy could not be assessed.
Results of a randomized, open-labeled comparative study in pediatric patients 4 months to 17 years of age with leukemia or lymphoma and a high risk for developing tumor lysis suggest that oral allopurinol may be slower and less effective in decreasing plasma uric acid concentrations than IV rasburicase. (See Uses: Chemotherapy-induced Hyperuricemia, in Rasburicase 44:00.) At the time of this study, IV allopurinol was unavailable. However, the different routes of administration for the drugs (i.e., oral versus IV) are not believed to account for the differences that were observed. Further study is needed to determine whether the more rapid control and reduction of plasma uric acid concentrations that is achieved with rasburicase therapy than is achieved with allopurinol therapy also will result in substantial decreases in metabolic complications and morbidity associated with tumor lysis syndrome, or the need for additional renal support (dialysis or hemofiltration).
Recurrent Renal Calculi
Allopurinol is used in the management of recurrent calcium oxalate renal calculi in males whose urinary urate excretion exceeds 800 mg daily and in females whose urinary urate excretion exceeds 750 mg daily. Therapy with the drug has reduced the rate of calculus events (passage of a new calculus or radiographic evidence of a new or enlarged calculus) and has prolonged the time to recurrence in patients with hyperuricosuria and normocalciuria and a history of recurrent calcium oxalate renal calculi. The use of allopurinol for this disorder must be carefully evaluated initially and reevaluated periodically to determine that therapy with the drug is beneficial and outweighs the risks. Clinical experience suggests that patients with recurrent calcium oxalate renal calculi may also benefit from dietary changes such as reductions in animal protein, sodium, refined sugars, oxalate-rich foods, and excessive calcium intake, as well as increases in oral fluids and dietary fiber. Allopurinol is also used for the prevention of uric acid renal calculi in patients with a history of recurrent stone formation.
Allopurinol has been used to reduce hyperuricemia secondary to glucose-6-phosphate dehydrogenase deficiency, Lesch-Nyhan syndrome, polycythemia vera, sarcoidosis, and secondary to the administration of thiazides or ethambutol.