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Medication Safety Issues
Sound-alike/look-alike issues:
Allopurinol may be confused with Apresoline
Zyloprim® may be confused with Xylo-Pfan®, ZORprin®
Pronunciation
(al oh PURE i nole)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
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
C
Pregnancy Implications
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”)
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
>1%:
Dermatologic: Rash (increased with ampicillin or amoxicillin use, 1.5% per manufacturer, >10% in some reports)
Gastrointestinal: Nausea (1.3%), vomiting (1.2%)
Renal: Renal failure/impairment (1.2%)
<1%: Hypersensitivity syndrome, alkaline phosphatase or hepatic transaminases increased, 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
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 to ~25% of the normal dose; monitor for toxic effects of azathioprine.
Chlorpropamide: Half-life of chlorpropamide may be increased.
Cyclosporine: Allopurinol may increase cyclosporine serum levels.
Mercaptopurine: Metabolism inhibited by allopurinol; reduce mercaptopurine dose to ~25% of the normal dose; monitor for toxic effects of mercaptopurine.
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: 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, 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
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.
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
Hemodialysis: Administer dose posthemodialysis or administer 50% supplemental dose
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
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 administer 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
Take as directed. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. While using this medication, do not use alcohol, other prescriptions, OTC medications, or vitamins without consulting prescriber. You may experience drowsiness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or heartburn (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or hair loss (reversible). Report skin rash or lesions; painful urination or blood in urine or stool; unresolved nausea or vomiting; numbness of extremities; pain or irritation of the eyes; swelling of lips, mouth, or tongue; unusual fatigue; easy bruising or bleeding; yellowing of skin or eyes; or any change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
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
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor laboratory values, effectiveness of therapy, and adverse reactions at beginning of therapy and periodically with long-term use. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report. considerations.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium: 500 mg
Aloprim™: 500 mg
Tablet: 100 mg, 300 mg
Zyloprim®: 100 mg, 300 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Zyloprim)
100 mg (30): $23.99
300 mg (30): $44.98
Extemporaneously Prepared
Crush tablets to make a 5 mg/mL suspension in simple syrup; stable 14 days under refrigeration
Nahata MC and Hipple TF, Pediatric Drug Formulations, 1st ed, Harvey Whitney Books Co, 1990.
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. The 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 April 2008
Content last modified April 2008
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