Saturday, March 15, 2008


U.S. BRAND NAMES — Aloprim™; Zyloprim®
PHARMACOLOGIC CATEGORY Xanthine Oxidase Inhibitor
DOSING: ADULTS — Doses >300 mg should be given in divided doses.
Gout: Oral: 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.
Secondary hyperuricemia associated with chemotherapy: Oral: 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 I.V.: 200-400 mg/m2/day (maximum: 600 mg/day) Note: 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.
Recurrent calcium oxalate stones: 200-300 mg/day in single or divided doses
(For additional information see "Allopurinol: Pediatric drug information")Gout: Children >10 years: Refer to adult dosing.
Recurrent calcium oxalate stones: Children >10 years: Refer to adult dosing.
Secondary hyperuricemia associated with chemotherapy: Oral: Children 10 years: 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, for prevention of acute uric acid nephropathy (begin 1-2 days before chemotherapy) Alternative (manufacturer labeling): <6>10 years: Refer to adult dosing. I.V.: Children 10 years: Starting dose: 200 mg/m2/day Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals. Adequate fluid intake and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable. Children >10 years: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 100 mg/day; increase until desired uric acid level is obtained. Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Must be adjusted due to accumulation of allopurinol and metabolites;
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 after hemodialysis or administer 50% supplemental dose.
I.V.: Clcr 10-20 mL/minute: Administer 200 mg/day. Clcr 3-10 mL/minute: Administer 100 mg/day. Clcr <3 mL/minute: Administer 100 mg/day at extended intervals.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as sodium (Aloprim™): 500 mg
Tablet (Zyloprim®): 100 mg, 300 mg
DOSAGE FORMS: CONCISE Injection, powder for reconstitution: 500 mg Aloprim™: 500 mg
Tablet: 100 mg, 300 mg Zyloprim®: 100 mg, 300 mg
ADMINISTRATION Oral: Should administer oral forms after meals with plenty of fluid.
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 interval.
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.
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
ADVERSE REACTIONS SIGNIFICANT >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% (Limited to important or life-threatening): Acute tubular necrosis, agranulocytosis, angioedema, aplastic anemia, bronchospasm, cataracts, exfoliative dermatitis, granuloma annulare, granulomatous hepatitis, hypersensitivity syndrome, interstitial nephritis, macular retinitis, nephrolithiasis, neuritis, pancreatitis, paresthesia, peripheral neuropathy, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxic pustuloderma, vasculitis
CONTRAINDICATIONS — Hypersensitivity to allopurinol or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Rash: Discontinue at first signs of rash.
Disease-related concerns: Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia. Renal impairment: Use with caution in patients with renal impairment; 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. Diuretics: Use with caution in patients taking diuretics concurrently. The risk of hypersensitivity may be increased in patients receiving thiazides.
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: 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.
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")
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).
PRICING — (data from (Zyloprim) 100 mg (30): $13.99 300 mg (30): $36.62
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.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — At high dosages, it is a theoretical possibility that oxypurinol stones could be formed but no record of such occurrence in overdose exists. Alkalinization of the urine and forced diuresis can help prevent potential xanthine stone formation.
CANADIAN BRAND NAMES — Alloprin®; Apo-Allopurinol®; Novo-Purol; Zyloprim®
INTERNATIONAL BRAND NAMES — Adenock (JP); Alinol (TH); Allo 300 (DE); Allo-Basan (CH); Allo-Puren (DE); Allohexal (AU); Allopin (TH); Alloprin (CA); Allopur (CH, NO); Allopurinol (MY, PL); Alloratio (PL); Alloril (IL); Allorin (NZ); Allosig (AU); Allozym (JP); Allupol (PL); Allurase (PH); Allurit (IT); Alopron (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Alopurinol (HR); Alositol (JP); Alpurase (PH); Alpurin (PH); Alunlan (PH, TW); Alurin (GT); Aluron (VE); Anoprolin (JP); Anzief (JP); Apo-Allopurinol (CA, PL); Aprinol (JP); Apurin (DK, FI, GR); Atisuril (MX); Benoxuric (ID); Bleminal (DE); Caplenal (GB, IE); Capurate (TW); Cellidrin (DE); Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Etindrax (MX); Foligan (CH, DE); Gichtex (AT); Hamarin (GB); Hycemia (ID); Isoric (ID); Ketanrift (JP); Ketobun-A (JP); Licoric (ID); Litinol (VE); Llanol (ID, PH); Lo-Uric (ZA); Lysuron 300 (CH); Masaton (JP); Medoric (TH); Mefanol (EC); Mephanol (AE, BF, BH, BJ, CH, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TZ, UG, YE, ZM, ZW); Milurit (BG, HK, HU, PL); Miniplanor (JP); Neufan (JP); Nipurol (VE); No-Uric (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Novo-Purol (CA); Progout (AU, CN, HK, NZ, SG); Proxuric (ID); Puricos (ZA); Purinol (IE, MY); Puristen (PH); Ranpuric (ZA); Remid (DE); Riball (JP); Rinolic (ID); Salterprim (ZA); Sinoric (ID); Takanarumin (JP); Tonsaric (TW); Trianol (PH); Uric (JP); Uricad (TH); Uricnol (ID); Uriconorm (CH); Urinol (MY); Uripurinol (DE); Urogquad (AR); Uroquad (AN, BB, BF, BJ, BM, BS, BZ, CI, ET, GH, GM, GN, GY, ID, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, SR, TT, TZ, UG, ZM, ZW); Urosin (AT, DE, EC); Vitralgin (PE); Xanturic (FR); Xanurace (PH); Xylonol (TW); Z300 (NZ); Zylapour (GR); Zylol (IL); Zyloprim (AN, AU, BB, BM, BS, BZ, CA, CR, DO, GT, GY, HN, JM, NI, PA, PH, PY, SR, SV, TT, ZA); Zyloric (AE, AR, BE, BF, BG, BH, BJ, BR, CH, CI, CL, CN, CY, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, HK, ID, IE, IN, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NO, OM, PE, PK, PL, PT, QA, RU, SA, SC, SD, SE, SL, SN, SY, TH, TW, TZ, UG, UY, VE, YE, ZM, ZW); Zyroric (KR)
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
PATIENT INFORMATION — Take after meals with plenty of fluid (at least 10-12 glasses of fluids per day); discontinue the drug and contact prescriber at first sign of rash, painful urination, blood in urine, irritation of the eyes, or swelling of the lips or mouth; may cause drowsiness; alcohol decreases effectiveness

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