Allopurinol


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Allopurinol
Allopurinol (Zyloprim)
Allopurinol
(al-oh- PYOUR-ih-nohl)
Pregnancy Category: C Alloprin Aloprim for Injection Apo-Allopurinol Novo-Purol Purinol Zyloprim (Rx)

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.

Drug Interactions: ACE inhibitors / Risk of hypersensitivity reactions Aluminum salts / Effect of allopurinol Ampicillin / Risk of drug-induced skin rashes Anticoagulants, oral / Anticoagulant effect R/T liver breakdown Azathioprine / Azthioprine effect R/T liver breakdown Cyclophosphamide / Risk of bleeding or infection due to drug myelosuppressive effects Iron preparations / Allopurinol hepatic iron concentrations Mercaptopurine / Mercaptopurine effect R/T liver breakdown Theophylline / Allopurinol plasma drug levels possible toxicity Thiazide diuretics / Risk of hypersensitivity reactions to allopurinol Uricosuric agents / Effect of oxipurinol due to rate of excretion

How Supplied: Injection: 500 mg/30mL; Tablet: 100 mg, 300 mg

Dosage
?IV infusion Lower serum uric acid in leukemia, lymphoma, or solid malignancies.
Adults: 200-400 mg/m 2/day, to a maximum of 600 mg/day. Children, initial: 200 mg/m 2/day. Reduce dose in those with impaired renal function as follows: C CR, 10-20 mL/min: 200 mg/day; C CR , 3-10mL/min: 100 mg/day; C CR, less than 30 mL/min: 100 mg/day at extended intervals.
?Tablets Gout/hyperuricemia.
Adults: 200-600 mg/day, depending on severity (minimum effective dose: 100-200 mg/day). Maximum daily dose should not exceed 800 mg.
Prevention of uric acid nephropathy during treatment of neoplasms.
Adults: 600-800 mg/day for 2-3 days (with high fluid intake).
Prophylaxis of acute gout.
Initial: 100 mg/day; increase by 100 mg at weekly intervals until serum uric acid level of 6 mg/100 mL or less is reached.
Hyperuricemia associated with malignancy.
Pediatric, 6-10 years of age: 300 mg/day either as a single dose of 100 mg t.i.d.; under 6 years of age: 150 mg/day in three divided doses.
Recurrent calcium oxalate calculi.
200-300 mg/day in one or more doses (dose may be adjusted according to urinary levels of uric acid).
To ameliorate granulocyte suppressant effect of fluorouracil.
600 mg/day.
Reduce perioperative mortality and postoperative arrhythmias in coronary artery bypass surgery.
300 mg 12 hr and 1 hr before surgery.
Reduce relapse rates of H. pylori-induced duodenal ulcers; treat hematemesis from NSAID-induced erosive gastritis.
50 mg q.i.d.
Alleviate pain due to acute pancreatitis.
50 mg q.i.d.
Treat American cutaneous leishmaniasis and T. cruzi.
20 mg/kg for 15 days.
Treat Chagas' disease.
600-900 mg/day for 60 days.
Alternative to treat epileptic seizures refractory to standard therapy.
300 mg/day, except use 150 mg/day in those less than 20 kg.
?Mouthwash Prevent fluorouracil-induced stomatitis.
20 mg in 3% methylcellulose (1 mg/mL).

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