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Pronunciation
(al oh PURE i nole)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
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
C
Pregnancy Considerations
There are few reports describing the use of allopurinol during pregnancy; no adverse fetal outcomes attributable to allopurinol have been reported in humans; use only if potential benefit outweighs the potential risk to the fetus.
Lactation
Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
Contraindications
Hypersensitivity to allopurinol or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash.
• Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression.
• Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with pre-existing hepatic impairment.
Disease-related concerns:
• Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia.
• Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. Dosage adjustments needed.
Concurrent drug therapy issues:
• ACE inhibitors: The risk of hypersensitivity may be increased in patients receiving ACE inhibitors.
• Amoxicillin/ampicillin: Risk of skin rash may be increased in patients receiving amoxicillin or ampicillin.
• Azathioprine/mercaptopurine: Use with caution in patients taking mercaptopurine or azathioprine; dosage adjustment necessary.
• Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
Adverse Reactions
Most commonly reported:
Dermatologic: Rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Alkaline phosphatase increased, liver enzymes increased
<1%: Abdominal pain, agranulocytosis, alopecia, angioedema, aplastic anemia, arthralgia, bronchospasm, cataracts, cholestatic jaundice, dermatitis (eczematoid, exfoliative, vascular bullous), dyspepsia, ecchymosis, eosinophilia, epistaxis, fever, gastritis, granuloma annulare, hepatitis, gynecomastia, headache, hepatic necrosis, hepatomegaly, hyperbilirubinemia, hypersensitivity reactions, leukocytosis, leukopenia, lichen planus, loss of taste perception, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, paresthesia, purpura, pruritus, renal failure, somnolence, Stevens-Johnson syndrome, taste perversion, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vomiting
Drug Interactions
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk D: Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
Anticonvulsants (Hydantoin): Allopurinol may increase the serum concentration of Anticonvulsants (Hydantoin). Risk C: Monitor therapy
AzaTHIOprine: Allopurinol may decrease the metabolism of AzaTHIOprine. Risk D: Consider therapy modification
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Risk C: Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination
Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Mercaptopurine: Allopurinol may decrease the metabolism of Mercaptopurine. Risk D: Consider therapy modification
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
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.
Storage
Powder for injection: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). Following reconstitution, intravenous solutions should be stored at 20°C to 25°C. 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).
Reconstitution
Further dilution with NS or D5W (50-100 mL) to ≤6 mg/mL is recommended.
Compatibility
Stable in D5W, NS, sterile water for injection.
Y-site administration: Compatible: Acyclovir, aminophylline, ampicillin, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, cefazolin, cefoperazone, cefotetan, ceftazidime, ceftizoxime, cefuroxime, cisplatin, cyclophosphamide, dactinomycin, dexamethasone sodium phosphate, doxorubicin liposome, enalaprilat, etoposide, famotidine, filgrastim, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, ganciclovir, granisetron, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, ifosfamide, lorazepam, mannitol, melphalan, mesna, methotrexate, metronidazole, miconazole, mitomycin, mitoxantrone, morphine, oxaliplatin, piperacillin, plicamycin, potassium chloride, ranitidine, sulfamethoxazole and trimethoprim, teniposide, thiotepa, 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. Variable (consult detailed reference): Ceftriaxone.
Compatibility in syringe: Incompatible: Ceftriaxone
Mechanism of Action
Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
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. Maximum daily dose: 800 mg/day.
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 (maximum: 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.
Adult Maintenance Doses of Allopurinol1
Creatinine Clearance
(mL/min)
Maintenance Dose of Allopurinol
(mg)
140
400 daily
120
350 daily
100
300 daily
80
250 daily
60
200 daily
40
150 daily
20
100 daily
10
100 every 2 days
0
100 every 3 days
1This table is based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/min.
Table has been converted to the following text.
Adult Maintenance Doses of Allopurinol
Note: Doses are based on a standard maintenance dose of 300 mg of allopurinol per day for a patient with a creatinine clearance of 100 mL/minute.
• Clcr 140 mL/minute: 400 mg daily
• Clcr 120 mL/minute: 350 mg daily
• Clcr 100 mL/minute: 300 mg daily
• Clcr 80 mL/minute: 250 mg daily
• Clcr 60 mL/minute: 200 mg daily
• Clcr 40 mL/minute: 150 mg daily
• Clcr 20 mL/minute: 100 mg daily
• Clcr 10 mL/minute: 100 mg every 2 days
• Clcr 0 mL/minute: 100 mg every 3 days
I.V.:
Clcr 10-20 mL/minute: 200 mg/day
Clcr 3-10 mL/minute: 100 mg/day
Clcr <3 mL/minute: 100 mg/day at extended intervals
Hemodialysis: Administer dose posthemodialysis or administer 50% supplemental dose
Administration: Oral
Should be administered after meals with plenty of fluid.
Administration: I.V.
Infuse over 15-60 minutes. 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 intervals.
Monitoring Parameters
CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy
Reference Range
Uric acid, serum: An increase occurs during childhood
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
Should take oral forms after meals with plenty of fluid. Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
Patient Education
Maintain adequate hydration, unless instructed to restrict fluid intake. Do not use alcohol. You may experience drowsiness, nausea, vomiting, heartburn, or hair loss (reversible). Report immediately skin rash or lesions; painful urination or blood in urine or stool; pain or irritation of the eyes; swelling of lips, mouth, or tongue; unusual fatigue; easy bruising or bleeding; yellowing of skin or eyes; any change in color of urine or stool; unresolved nausea or vomiting; or numbness of extremities.
Geriatric Considerations
Adjust dose based on renal function.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness
Mental Health: Effects on Psychiatric Treatment
Rarely may cause bone marrow suppression; use caution with clozapine and carbamazepine
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg (base)
Aloprim®: 500 mg (base)
Tablet, oral: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Allopurinol)
100 mg (100): $13.99
300 mg (100): $22.99
Tablets (Zyloprim)
100 mg (30): $39.99
300 mg (30): $79.99
Extemporaneously Prepared
A 20 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus® or a 1:4 mixture of cherry syrup concentrate and simple syrup, NF. Crush eight 300 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well”. Stable for 60 days refrigerated or at room temperature (Allen, 1996; Nahata, 2004).
Allen LV Jr and Erickson MA 3rd, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53(16):1944-9.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
References
Allen LV and Erickson MA 3d, “Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,” Am J Health Syst Pharm, 1996, 53(16):1944-9.
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Appelbaum SJ, Mayersohn M, Dorr RT, et al, “Allopurinol Kinetics and Bioavailability. Intravenous, Oral and Rectal Administration,” Cancer Chemother Pharmacol, 1982, 8(1):93-8.
Bennett WM, Aronoff GR, Golper TA, et al, Drug Prescribing in Renal Failure, Philadelphia, PA: American College of Physicians, 1987.
Day RO, Birkett DJ, Hicks M, et al, “New Uses for Allopurinol,” Drugs, 1994, 48(3):399-44.
Elasy T, Kaminsky D, Tracy M, et al, “Allopurinol Hypersensitivity Syndrome Revisited,” West J Med, 1995, 162(4):360-1.
Emmerson BT, “The Management of Gout,” N Engl J Med, 1996, 334(7):445-51.
Ferner RE, Simmonds HA, and Bateman DN, “Allopurinol Kinetics After Massive Overdose,” Hum Toxicol, 1988, 7(3):293-4.
Hande KR and Garrow GC, “Acute Tumor Lysis Syndrome in Patients With High-Grade Non-Hodgkin's Lymphoma,” Am J Med, 1993, 94(2):133-9.
Krakoff IH and Murphy ML, “Hyperuricemia in Neoplastic Disease in Children: Prevention With Allopurinol, A Xanthine Oxidase Inhibitor,” Pediatrics, 1968, 41(1):52-6.
McInnes GT, Lawson DH, and Jick H, “Acute Adverse Reactions Attributed to Allopurinol in Hospitalized Patients,” Ann Rheum Dis, 1981, 40(3):245-9.
Murrell GA and Rapeport WG, “Clinical Pharmacokinetics of Allopurinol,” Clin Pharmacokinet, 1986, 11(5):343-53.
Parra E, Gota R, Gamen A, et al, “Granulomatous Interstitial Nephritis Secondary to Allopurinol Treatment,” Clin Nephrol, 1995, 43(5):350.
Vinciullo C, “Allopurinol Hypersensitivity,” Med J Aust, 1984, 141(7):449-50.
International Brand Names
Lexi-Comp.com
Last full review/revision June 2011
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