indication

For the treatment of hyperuricemia associated with primary or secondary gout. Also indicated for the treatment of primary or secondary uric acid nephropathy, with or without the symptoms of gout, as well as chemotherapy-induced hyperuricemia and recurrent renal calculi.

pharmacology

Allopurinol, a structural analog of the natural purine base hypoxanthine, is used to prevent gout and renal calculi due to either uric acid or calcium oxalate and to treat uric acid nephropathy, hyperuricemia, and some solid tumors.

mechanism of action

Allopurinol and its active metabolite, oxypurinol, inhibits the enzyme xanthine oxidase, blocking the conversion of the oxypurines hypoxanthine and xanthine to uric acid. Elevated concentrations of oxypurine and oxypurine inhibition of xanthine oxidase through negative feedback results in a decrease in the concentrations of uric acid in the serum and urine. Allopurinol also facilitates the incorporation of hypoxanthine and xanthine into DNA and RNA, leading to a feedback inhibition of de novo purin synthesis and a decrease in serum uric acid concentrations as a result of an increase in nucleotide concentration.

toxicity

LD₅₀=214 mg/kg (in mice)

biotransformation

Hepatic

absorption

Approximately 80-90% absorbed from the gastrointestinal tract.

half life

1-3 hours

route of elimination

Approximately 20% of the ingested allopurinol is excreted in the feces.

drug interactions

Acenocoumarol: Allopurinol may increase the anticoagulant effect of acenocoumarol.

Anisindione: Allopurinol may increase the anticoagulant effect of anisindione.

Azathioprine: Allopurinol may increase the effect of thiopurine, azathioprine.

Cyclosporine: Allopurinol increases the effect and toxicity of cyclosporine

Dicumarol: Allopurinol may increase the anticoagulant effect of dicumarol.

Mercaptopurine: Allopurinol may increase the effect of thiopurine, mercaptopurine.

Trandolapril: The ACE inhibitor, Trandolapril, may increase the risk of hypersensitivity reactions to Allopurinol.

Warfarin: Allopurinol may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin times and therapeutic effects of warfarin if allopurinol is initiated, discontinued or dose changed.