allopurinol
Purinol ◆, Zyloprim

allopurinol sodium
Aloprim

Available forms
Available by prescription only
Injection: 500 mg/30-ml vials
Tablets (scored): 100 mg, 200 mg ◆, 300 mg

Indications and dosages
 Gout, primary or secondary hyperuricemia.  Dosage varies with severity of disease; drug can be given as single dose or divided but should be divided if dose is larger than 300 mg.
Adults: Mild gout, 200 to 300 mg P.O. daily; severe gout with large tophi, 400 to 600 mg P.O. daily. Same dose for maintenance in secondary hyperuricemia.
 Hyperuricemia secondary to malignancies. Children ages 6 to 10: 300 mg P.O. daily (100 mg t.i.d.).
Children younger than age 6: 150 mg P.O. daily (50 mg t.i.d.).
 Prevention of acute gouty attacks. Adults: 100 mg P.O. daily; increase at weekly intervals by 100 mg without exceeding maximum dose (800 mg) until serum uric acid level decreases to 6 mg/dl or less.
 Prevention of uric acid nephropathy during cancer chemotherapy. Adults: 600 to 800 mg P.O. daily for 2 to 3 days in conjunction with high fluid intake. In those who can’t tolerate oral therapy, 200 to 400 mg/m² I.V. daily as a single infusion or in divided infusions at 6-, 8-, or 12-hour intervals. Maximum daily I.V. dose is 600 mg.
Children: 200 mg/m² I.V. daily as a single infusion or in divided infusions at 6-, 8-, or 12-hour intervals.
≡ Dosage adjustment. For I.V. allopurinol sodium in patients with a creatinine clearance of less than 3 ml/minute, give 100 mg daily at extended intervals. For creatinine clearance of 3 to 10 ml/ minute, give 100 mg daily. For 10 to 20 ml/minute, give 200 mg daily.
 Recurrent calcium oxalate calculi. Adults: 200 to 300 mg P.O. daily in single dose or divided doses.
≡ Dosage adjustment. For adults with creatinine clearance up to 9 ml/minute, give 100 mg P.O. q 3 days. For creatinine clearance of 10 to 19 ml/ minute, give 100 mg P.O. every other day. For 20 to 39 ml/minute, give 100 mg P.O. daily. For 40 to 59 ml/minute, give 150 mg P.O. daily. For 60 to 79 ml/ minute, give 200 mg P.O. daily. For 80 ml/minute, give 250 mg P.O. daily.

Pharmacodynamics
Antigout action: Allopurinol inhibits xanthine oxidase, the enzyme catalyzing the conversion of hypoxanthine to xanthine, and the conversion of xanthine to uric acid. By blocking this enzyme, allopurinol and its metabolite, oxypurinol, prevent the conversion of oxypurines (xanthine and hypoxanthine) to uric acid, thus decreasing serum and urine levels of uric acid. Drug has no analgesic, anti-inflammatory, or uricosuric action.

Pharmacokinetics
Absorption: After oral administration, about 80% to 90% of dose is absorbed.
Distribution: Distributed widely throughout the body except in the brain, where drug levels are 50% of those found in the rest of the body. Allopurinol and oxypurinol aren’t bound to plasma proteins.
Metabolism: Metabolized to oxypurinol by xanthine oxidase. Half-life of allopurinol is 1 to 2 hours; half-life of oxypurinol, about 15 hours.
Excretion: 5% to 7% of allopurinol dose is excreted in the urine unchanged within 6 hours of ingestion. Afterward, it’s excreted by the kidneys as oxypurinol, allopurinol, and oxypurinol ribonucleosides. About 70% of the administered daily dose is excreted in the urine as oxypurinol and an additional 2% appears in the feces as unchanged drug within 48 to 72 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with idiopathic hemochromatosis.

Interactions
Drug-drug. Amoxicillin, ampicillin: May increase risk of rash. Monitor patient for this effect.
Azathioprine, mercaptopurine: May increase toxic effects of these drugs, particularly bone marrow depression. Combined use of these drugs requires reduction of initial doses of azathioprine or mercaptopurine to 25% to 33% of the usual dose, with subsequent doses adjusted according to patient response and toxic effects.
Chlorpropamide: Allopurinol or its metabolites may compete with chlorpropamide for renal tubular secretion. Monitor patient for signs of excessive hypoglycemia if used together.
Co-trimoxazole: May cause thrombocytopenia. Monitor CBC with platelets.
Cyclophosphamide: May increase risk of bone marrow depression. Monitor patient for this effect.
Dicumarol: Inhibits hepatic microsomal metabolism of dicumarol, thus increasing half-life of dicumarol. Monitor patient for increased anticoagulant effects.
Theophylline: Theophylline clearance can decrease with large doses (600 mg daily), leading to increased plasma theophylline level. Monitor drug levels.
Thiazide diuretics: May increase risk of allopurinol-induced hypersensitivity reactions in patients with decreased renal function. Use together cautiously.

Adverse reactions
CNS: drowsiness, headache, paresthesia, peripheral neuropathy, neuritis, fever.
CV: hypersensitivity vasculitis, necrotizing angiitis.
EENT: epistaxis.
GI: nausea, vomiting, diarrhea, abdominal pain, gastritis, dyspepsia, taste loss or perversion.
GU: renal failure, uremia.
Hematologic: agranulocytosis, anemia, aplastic anemia, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, ecchymoses.
Hepatic: hepatitis, hepatic necrosis, hepatomegaly, cholestatic jaundice.
Musculoskeletal: arthralgia, myopathy.
Skin: alopecia; rash (usually maculopapular); exfoliative, urticarial, and purpuric lesions; Stevens-Johnson syndrome; erythema multiforme; severe furunculosis of nose; ichthyosis; toxic epidermal necrolysis.
Other: chills.

Effects on lab test results
• May increase alkaline phosphatase, AST, and ALT levels.
• May increase eosinophil count. May decrease hemoglobin and granulocyte and platelet counts. May increase or decrease WBC count.

Overdose and treatment
No information available.

Special considerations
• Gout may be secondary to diseases such as acute or chronic leukemia, polycythemia vera, multiple myeloma, or psoriasis or to administration of chemotherapeutic drug.
• Rash occurs mostly in patients taking diuretics and in those with renal disorders.
• If renal insufficiency occurs during treatment, reduce allopurinol dose.
• Acute gouty attacks may occur in first 6 weeks of therapy; concurrent use of colchicine or another anti-inflammatory may be prescribed prophylactically.
• Monitor patient’s intake and output. Daily urine output of at least 2 L and maintenance of neutral or slightly alkaline urine is desirable.
• Monitor CBC, serum uric acid levels, and hepatic and renal function at start of therapy and periodically thereafter.
• Minimize GI adverse reactions by administering drug with meals or immediately after. Tablets may be crushed and administered with fluid or food.
• Allopurinol may predispose patient to ampicillin-induced rash if taken together.
• Allopurinol-induced rash may occur weeks after discontinuation of drug.
• When allopurinol is added to a therapeutic regimen of colchicine, uricosuric agents, or anti-inflammatories, it may take months to discontinue the latter drugs.
• Allopurinol has been used to reduce hyperuricemia resulting from G6PD deficiency, Lesch-Nyhan syndrome, polycythemia vera, sarcoidosis, and administration of thiazides or ethambutol.
• Preparation of allopurinol sodium includes reconstitution and dilution. Dissolve each 30-ml vial with 25 ml of sterile water for injection. Dilute this solution to a desired concentration (no greater than 6 mg/ml) with normal saline solution or D₅W. Solutions containing sodium bicarbonate shouldn’t be used. Store at 68° to 77° F (20° to 25° C) and use within 10 hours. Don’t use if particulate matter or discoloration is present. Refer to package insert for a full list of drugs with which Aloprim is incompatible in solution.
Breast-feeding patients
• Because oxypurinol and allopurinol appear in breast milk, use allopurinol with extreme caution in breast-feeding women.
Pediatric patients
• Don’t use drug in children except to treat hyperuricemia resulting from malignancies.
Geriatric patients
• Follow dosage recommendations for adults. Watch for renal disorders or impaired renal function and treat according to dosage recommendations for patients with impaired renal function.

Patient education
• Encourage patient to drink 10 to 12 8-oz (240-ml) glasses of water daily while taking drug unless otherwise contraindicated.
• When using drug to treat recurrent calcium oxalate stones, advise patient to reduce dietary intake of animal protein, sodium, refined sugars, vitamin C, oxalate-rich foods, and calcium.
• Advise patient to avoid hazardous activities requiring alertness until CNS response to drug is known because drowsiness may occur.
• Tell patient to report all adverse reactions immediately.
• Advise patient to take a missed dose when it’s remembered unless it’s time for next scheduled dose; he shouldn’t double the dose.
• Tell patient to discontinue drug and call at first sign of rash or other allergic reaction.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use