Classification: Antigout agent
Action/Kinetics: Allopurinol and its major metabolite, oxipurinol, are potent inhibitors of xanthine oxidase, an enzyme involved in the synthesis of uric acid, without disrupting the biosynthesis of essential purine. This results in decreased levels of uric acid. The drug also increases reutilization of xanthine and hypoxanthine for synthesis of nucleotide and nucleic acid synthesis by acting on the enzyme hypoxanthine-guanine phosphoribosyltransferase. The resultant increases in nucleotides cause a negative feedback to inhibit synthesis of purines and a decrease in uric acid levels. Peak plasma levels, after PO: 1.5 hr for allopurinol and 4.5 hr for oxipurinol. Onset, after PO: 2-3 days. t½, after PO; (allopurinol); 1-3 hr; t 1/2 (oxipurinol): 12-30 hr. Peak serum levels after PO, allopurinol: 2-3 mcg/mL; oxipurinol: 5-6.5 mcg/mL (up to 50 mcg/mL in clients with impaired renal function). Maximum therapeutic effect, after PO: 1-3 weeks. Well absorbed from GI tract, metabolized in liver, excreted in urine and feces (20%).
Uses: IV: Leukemia, lymphoma, and solid tumor malignancies receiving cancer chemotherapy and which cause elevations of serum and urinary uric acid levels and who cannot tolerate PO therapy. PO: Primary or secondary gout (acute attacks, tophi, joint destruction, nephropathy, uric acid lithiasis). Clients with leukemia, lymphoma, or other malignancies in whom drug therapy causes elevations of serum and urinary uric acid. Recurrent calcium oxalate calculi where daily uric acid excretion exceeds 800 mg/day in males and 750 mg/day in females. Investigational: Mixed with methylcellulose as a mouthwash to prevent stomatitis following fluorouracil administration. Reduce the granulocyte suppressant effect of fluorouracil. Prevent ischemic reperfusion tissue damage. Reduce the incidence of perioperative mortality and postoperative arrhythmias in coronary artery bypass surgery. Reduce the rates of Helicobacter pylori-induced duodenal ulcers and treatment of hematemesis from NSAID-induced erosive esophagitis. Alleviate pain due to acute pancreatitis. Treatment of American cutaneous leishmaniasis and against Trypanosoma cruzi. Treat Chagas' disease. As an alternative in epileptic seizures refractory to standard therapy.
Contraindications: Hypersensitivity to drug. Clients with idiopathic hemochromatosis or relatives of clients suffering from this condition. Children except as an adjunct in treatment of neoplastic disease. Severe skin reactions on previous exposure. To treat asymptomatic hyperuricemia.
Special Concerns: Use with caution during lactation and in clients with liver or renal disease. In children use has been limited to rare inborn errors of purine metabolism or hyperuricemia as a result of malignancy or cancer therapy.
Side Effects: Dermatologic (most frequent): Pruritic maculopapular skin rash (may be accompanied by fever and malaise). Vesicular bullous dermatitis, eczematoid dermatitis, pruritus, urticaria, onycholysis, purpura, lichen planus, Stevens-Johnson syndrome, toxic epidermal necrolysis. Skin rash has been accompanied by hypertension and cataract development. Allergy: Fever, chills, leukopenia, eosinophilia, arthralgia, skin rash, pruritus, N&V, nephritis. GI: N&V, diarrhea, gastritis, dyspepsia, abdominal pain (intermittent). Hematologic: Leukopenia, eosinophilia, thrombocytopenia, leukocytosis. Hepatic: Hepatomegaly, cholestatic jaundice, hepatic necrosis granulomatous hepatitis. Neurologic: Headache, peripheral neuropathy, paresthesia, somnolence, neuritis. CV: Necrotizing angiitis, hypersensitivity vasculitis. Miscellaneous: Ecchymosis, epistaxis, taste loss, arthralgia, acute attacks of gout, fever, myopathy, renal failure, uremia, alopecia.
Laboratory Test Alterations: ALT, AST, alkaline phosphatase. Serum cholesterol. Serum glucose levels.
How Supplied: Injection: 500 mg/30mL; Tablet: 100 mg, 300 mg