Pronunciation:

(al oh PURE i nole)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Oral: Prevention of attack of gouty arthritis and nephropathy; treatment of secondary hyperuricemia which may occur during treatment of tumors or leukemia; prevention of recurrent calcium oxalate calculi

I.V.: Treatment of elevated serum and urinary uric acid levels when oral therapy is not tolerated in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer chemotherapy

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

>1%:

Dermatologic: Rash (1.5%)

Gastrointestinal: Nausea (1.3%), vomiting (1.2%)

Renal: Renal failure/impairment (1.2%)

<1%: Hypersensitivity syndrome, increased alkaline phosphatase or hepatic transaminases, granulomatous hepatitis, dyspepsia, pancreatitis, gynecomastia, agranulocytosis, aplastic anemia, acute tubular necrosis, interstitial nephritis, nephrolithiasis, vasculitis, toxic epidermal necrolysis, exfoliative dermatitis, Stevens-Johnson syndrome, granuloma annulare, toxic pustuloderma, peripheral neuropathy, neuritis, paresthesia, bronchospasm, cataracts, macular retinitis, angioedema, epistaxis

Overdosage/Toxicology:

Drug Interactions:

Ampicillin, amoxicillin: Incidence of rash may be increased.

Anticoagulants: Allopurinol may prolong the half-life of anticoagulants, effect seen with dicumarol; monitor.

ACE inhibitors: Captopril may increase risk of hypersensitivity.

Azathioprine: Metabolism inhibited by allopurinol; reduce azathioprine dose by ¹/3 or ¹/4.

Chlorpropamide: Half-life of chlorpropamide may be increased.

Cyclosporine: Allopurinol may increase cyclosporine serum levels.

Mercaptopurine: Metabolism inhibited by allopurinol; reduce mercaptopurine dose by ¹/3 or ¹/4.

Thiazide diuretics: Toxicity and risk of hypersensitivity may be increased.

Theophylline: Half-life of theophylline may be increased.

Vidarabine: Neurotoxicity may be enhanced.

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may decrease effectiveness).

Iron supplements: Hepatic iron uptake may be increased.

Vitamin C: Large amounts of vitamin C may acidify urine and increase kidney stone formation.

Stability:

Powder for injection: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). Allopurinol sodium for injection should be dissolved with 25 mL of sterile water for injection. It may then be added to NS or D5W. A final concentration of no greater than 6 mg/mL is recommended. Following reconstitution, intravenous solutions should be stored at 20°C to 25°C (68°F to 77°F). Do not refrigerate reconstituted and/or diluted product. Must be administered within 10 hours of solution preparation.

Tablet: Store at controlled room temperature of 15°C to 25°C (59°F to 77°F).

Compatibility:

Y-site administration: Compatible: Acyclovir, aminophylline, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cisplatin, co-trimoxazole, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, fluconazole, fludarabine, fluorouracil, furosemide, ganciclovir, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, mesna, methotrexate, metronidazole, mitoxantrone, morphine, piperacillin, plicamycin, potassium chloride, ranitidine, thiotepa, ticarcillin, ticarcillin/clavulanate, vancomycin, vinblastine, vincristine, zidovudine. Incompatible: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine

Mechanism of Action:

Pharmacodynamics/Kinetics:

Onset of action: Peak effect: 1-2 weeks

Absorption: Oral: ~80%; Rectal: Poor and erratic

Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg; enters breast milk

Protein binding: <1%

Metabolism: ~75% to active metabolites, chiefly oxypurinol

Bioavailability: 49% to 53%

Half-life elimination:

Normal renal function: Parent drug: 1-3 hours; Oxypurinol: 18-30 hours

End-stage renal disease: Prolonged

Time to peak, plasma: Oral: 30-120 minutes

Excretion: Urine (76% as oxypurinol, 12% as unchanged drug)

Allopurinol and oxypurinol are dialyzable

Dosage:

Oral: Doses >300 mg should be given in divided doses.

Children 10 years: Secondary hyperuricemia associated with chemotherapy: 10 mg/kg/day in 2-3 divided doses or 200-300 mg/m²/day in 2-4 divided doses, maximum: 800 mg/24 hours

Alternative (manufacturer labeling): <6 years: 150 mg/day in 3 divided doses; 6-10 years: 300 mg/day in 2-3 divided doses

Children >10 years and Adults:

Secondary hyperuricemia associated with chemotherapy: 600-800 mg/day in 2-3 divided doses for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days before chemotherapy

Gout: Mild: 200-300 mg/day; Severe: 400-600 mg/day; to reduce the possibility of acute gouty attacks, initiate dose at 100 mg/day and increase weekly to recommended dosage.

Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses

Elderly: Initial: 100 mg/day, increase until desired uric acid level is obtained

I.V.: Hyperuricemia secondary to chemotherapy: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.

Children 10 years: Starting dose: 200 mg/m²/day

Children >10 years and Adults: 200-400 mg/m²/day (max: 600 mg/day)

Dosing adjustment in renal impairment: Must be adjusted due to accumulation of allopurinol and metabolites:

Oral: Removed by hemodialysis; adult maintenance doses of allopurinol (mg) based on creatinine clearance (mL/minute): See table.

Creatinine Clearance
(mL/min):

Administration:

Oral: Should administer oral forms after meals with plenty of fluid.

I.V.: The rate of infusion depends on the volume of the infusion. Whenever possible, therapy should be initiated at 24-48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). I.V. daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.

Monitoring Parameters:

Reference Range:

Adults:

Male: 3.4-7 mg/dL or slightly more

Female: 2.4-6 mg/dL or slightly more

Values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.

Dietary Considerations:

Patient Education:

Nursing Implications:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Oncology: Emetic Potential:

Oncology: Vesicant:

Dosage Forms:

Injection, powder for reconstitution, as sodium (Aloprim™): 500 mg

Tablet (Zyloprim®): 100 mg, 300 mg

Extemporaneously Prepared:

Nahata MC and Hipple TF, Pediatric Drug Formulations, 1st ed, Harvey Whitney Books Co, 1990.

International Brand Names: