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Pronunciation
(al oh PURE i nole)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral: Management of primary or secondary gout (acute attack, tophi, joint destruction, uric acid lithiasis, and/or nephropathy); management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies; management of recurrent calcium oxalate calculi (with uric acid excretion >800 mg/day in men and >750 mg/day in women)
I.V.: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies
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.
Other warnings/precautions:
• Appropriate use: Full effect on serum uric acid levels in chronic gout may take several weeks to become evident; gradual titration is recommended.
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
Metabolism/Transport Effects
None known.
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 Oxypurinol, 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 Oxypurinol, 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 20°C to 25°C (68°F to 77°F). Following preparation, 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 20°C to 25°C (68°F to 77°F). Protect from moisture and light.
Reconstitution
Reconstitute powder for injection with SWFI. 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, cefotetan, ceftazidime, 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, mitomycin, mitoxantrone, morphine, oxaliplatin, piperacillin, 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, 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: Note: Doses >300 mg should be given in divided doses.
Management of hyperuricemia associated with chemotherapy:
Manufacturer's labeling:
Children <6 years: 150 mg/day
Children 6-10 years: 300 mg/day
Children >10 years and Adults: 600-800 mg/day in 2-3 divided doses
Alternative recommendations (unlabeled dosing; intermediate-risk for tumor lysis syndrome): Children and Adults: Intermediate-risk for tumor lysis syndrome: 10 mg/kg/day (maximum dose/day: 800 mg) in 3 divided doses or 50-100 mg/m2 every 8 hours (maximum dose: 300 mg/m2/day), begin 1-2 days before initiation of induction chemotherapy; may continue for 3-7 days after chemotherapy (Coiffier, 2008)
Gout (chronic): Adults:
Manufacturer's labeling: 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, also consider using low-dose colchicine or an NSAID to reduce the risk of a gouty attack. Maximum daily dose: 800 mg/day.
Alternative recommendations (unlabeled dosing): Initial: 100 mg/day, increasing the dose gradually every 4 weeks, while monitoring plasma uric acid levels to achieve a goal of <6 mg/dL; dosages of 600 mg/day and rarely, 900 mg/day may be required (McGill, 2010) or Initial: 100 mg/day, increasing the dose by 100 mg/day at 2-4 weeks intervals as required to achieve desired uric acid level of ≤6 mg/dL (EULAR gout guidelines; Zhang, 2006).
Recurrent calcium oxalate stones: Adults: 200-300 mg/day in single or divided doses
I.V.:
Management of hyperuricemia associated with chemotherapy: Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals.
Manufacturer's labeling:
Children: Starting dose: 200 mg/m2/day beginning 1-2 days before chemotherapy
Adults: 200-400 mg/m2/day (maximum: 600 mg/day) beginning 1-2 days before chemotherapy
Alternative recommendations (unlabeled dosing; intermediate-risk for tumor lysis syndrome): Children and Adults: 200-400 mg/m2/day (maximum dose/day: 600 mg) in 1-3 divided doses beginning 1-2 days before the start of induction chemotherapy; may continue for 3-7 days after chemotherapy (Coiffier, 2008)
Note: Adequate fluid intake is desirable. A fluid intake sufficient to yield a daily urinary output of at least 2 L in adults is desirable.
Dosing adjustment in renal impairment:
Manufacturer's labeling: Oral, I.V.: Lower doses are required in renal impairment due to potential for accumulation of allopurinol and metabolites.
Clcr 10-20 mL/minute: 200 mg/day
Clcr 3-10 mL/minute: ≤100 mg/day
Clcr <3 mL/minute: 100 mg/dose at extended intervals
Alternative recommendations (unlabeled dosing):
Management of hyperuricemia associated with chemotherapy: Dosage reduction of 50% is recommended in renal impairment (Coiffier, 2008)
Gout: Oral:
Initiate therapy with 50-100 mg daily, and gradually increase to a maintenance dose to achieve a serum uric acid level of ≤6 mg/dL (with close monitoring of serum uric acid levels and for hypersensitivity) (Dalbeth, 2007).
Hemodialysis: Initial: 100 mg alternate days given postdialysis, increase cautiously to 300 mg based on response. If dialysis is on a daily basis, an additional 50% of the dose may be required postdialysis (Dalbeth, 2007)
Administration: Oral
Do not initiate or discontinue allopurinol during an acute gout attack. Should be administered after meals with plenty of fluid.
Administration: I.V.
The rate of infusion depends on the volume of the infusion; infuse maximum single daily doses (600 mg/day) over ≥30 minutes. 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
CBC, serum uric acid levels, I & O, hepatic and renal function, especially at start of therapy; signs and symptoms of hypersensitivity
Reference Range
Uric acid, serum: An increase occurs during childhood
Adults:
Males: 3.4-7 mg/dL or slightly more
Females: 2.4-6 mg/dL or slightly more
Target: ≤6 mg/dL
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. Avoid the use of alcohol (especially beer). 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. Continue medication during gout attacks.
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): $23.99
Tablets (Zyloprim)
100 mg (30): $69.98
300 mg (30): $103.99
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.
Coiffier B, Altman A, Pui CH, et al, “Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review,” J Clin Oncol, 2008, 26(16):2767-78.
Dalbeth N and Stamp L, “Allopurinol Dosing in Renal Impairment: Walking the Tightrope Between Adequate Urate Lowering and Adverse Events,” Semin Dial, 2007, 20(5):391-5.
Day RO, Graham GG, Hicks M, et al, “Clinical Pharmacokinetics and Pharmacodynamics of Allopurinol and Oxypurinol,” Clin Pharmacokinet, 2007, 46(8):623-44.
Elasy T, Kaminsky D, Tracy M, et al, “Allopurinol Hypersensitivity Syndrome Revisited,” West J Med, 1995, 162(4):360-1.
El-Zawawy H and Mandell BF, “Managing Gout: How is it Different in Patients With Chronic Kidney Disease?” Cleve Clin J Med, 2010, 77(12):919-28.
Emmerson BT, “The Management of Gout,” N Engl J Med, 1996, 334(7):445-51.
Fravel MA and Ernst ME, “Management of Gout in the Older Adult,” Am J Geriatr Pharmacother, 2011, 9(5):271-85.
Gahart BL and Nazareno AR, 2012 Intravenous Medications: A Handbook for Nurses and Health Professionals, 28th ed, St Louis, MO: Elsevier/Mosby, 2012, 58-9.
Hande KR, Noone RM, and Stone WJ, “Severe Allopurinol Toxicity,” Am J Med, 1984, 76(1):47-56.
McGill NW, “Management of Gout: Beyond Allopurinol,” Int Med J, 2010, 40(8):545-53.
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.
Stamp LK, O'Donnell JL, Zhang M, et al, “Using Allopurinol Above the Dose Based on Creatinine Clearance Is Effective and Safe in Patients With Chronic gout, Including Those With Renal Impairment,” Arthritis Rheum, 2011, 63(2):412-21.
Zhang W, Doherty M, Bardin T, et al, “EULAR Evidence Based Recommendations for Gout. Part II: Management. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT),” Ann Rheum Dis, 2006, 65(10):1312-24.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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