Allopurinol

IV

(al -oh - PY OU R - ih -n o hl )
CLASSIFICATION(S): Antigout drug PREGNANCY CATEGORY: C Rx: Aloprim for Injection, Zyloprim. WRx: Apo-Allopurinol.
USES IV: Management of clients with leukemia, lymphoma, and solid tumor malignancies in whom cancer chemotherapy causes elevations of serum and urinary uric acid levels and who cannot tolerate PO therapy. PO: (1) Primary or secondary gout (acute attacks, tophi, joint destruction, nephropathy, uric acid lithiasis). (2) Clients with leukemia, lymphoma, or other malignancies in whom drug therapy causes elevations of serum and urinary uric acid. Recurrent calcium oxalate calculi where daily uric acid excretion exceeds 800 mg/day in males and 750 mg/day in females. Investigational: Mixed with methylcellulose as a mouthwash to prevent stomatitis following fluorouracil administration. Reduce granulocyte suppressant effect of fluorouracil. Prevent ischemic reperfusion tissue damage. Reduce the incidence of perioperative mortality and postoperative arrhythmias in coronary artery bypass surgery. Reduce rates of Helicobacter pylori-induced duodenal ulcers and treatment of hematemesis from NSAID-induced erosive esophagitis. Alleviate pain due to acute pancreatitis. Treatment of American cutaneous leishmaniasis and against Trypanosoma cruzi. Treat Chagas disease. As an alternative in epileptic seizures refractory to standard therapy. ACTION/KINETICS Action Allopurinol and its major metabolite, oxipurinol, are potent inhibitors of xanthine oxidase, an enzyme involved in the synthesis of uric acid. Results in decreased uric acid levels. Also allopurinol

increases reutilization of xanthine and hypoxanthine for synthesis of nucleotide and nucleic acid by acting on the enzyme hypoxanthine-guanine phosphoribosyltransferase. The resultant increases in nucleotides cause a negative feedback to inhibit synthesis of purines and a decrease in uric acid levels. Pharmacokinetics Peak plasma levels, after PO: 1.5 hr for allopurinol and 4.5 hr for oxipurinol. 1 Onset, after PO: 23 days. t /2, after PO 1 (allopurinol); 13 hr; t /2 (oxipurinol): 1230 hr. Peak serum levels after PO, allopurinol: 23 mcg/mL; oxipurinol: 56.5 mcg/mL (up to 50 mcg/mL in clients with impaired renal function). Maximum therapeutic effect, after PO: 13 weeks. Well absorbed from GI tract, metabolized in liver, excreted in urine and feces (20%). CONTRAINDICATIONS Hypersensitivity to drug. Clients with idiopathic hemochromatosis or relatives of clients suffering from this condition. Children except as an adjunct in treatment of neoplastic disease. Severe skin reactions on previous exposure. To treat asymptomatic hyperuricemia. SPECIAL CONCERNS Use with caution during lactation and in clients with liver or renal disease. In children use has been limited to rare inborn errors of purine metabolism or hyperuricemia as a result of malignancy or cancer therapy. SIDE EFFECTS Most Common Rash, N&V, renal failure/insufficiency. Dermatologic: Pruritic maculopapular skin rash (may be accompanied by fever and malaise). Vesicular bullous dermatitis, eczematoid dermatitis, pruritus, urticaria, onycholysis, purpura, lichen planus, Stevens-Johnson syndrome, toxic epidermal necrolysis. Skin rash has been accompanied by hypertension and cataract development. Allergic: Fever, chills, leukopenia, eosinophilia, arthralgia, skin rash, pruritus, N&V, nephritis. GI: N&V, diarrhea, GI bleeding, splenomegaly, intestinal obstruction, flatulence, constipation, proctitis, gastritis, dyspepsia, abdominal pain (inIV = Intravenous

C = see color insert

H = Herbal

E = sound alike drug

ALLOPURINOL
1 Chlorpropamide / t /2 of chlorpropamide hypoglycemia Cyclophosphamide / Risk of bleeding or infection due to drug myelosuppressive effects Cyclosporine / Cyclosporine levels Iron preparations / Allopurinol hepatic iron concentrations Mercaptopurine / Mercaptopurine effects and toxicity R/T liver breakdown Theophylline / Allopurinol plasma drug levels possible toxicity Thiazide diuretics / Risk of hypersensitivity reactions to allopurinol Uricosuric agents / Effect of oxipurinol R/T rate of excretion HOW SUPPLIED Injection: 500 mg/30 mL; Tablets: 100 mg, 300 mg. DOSAGE IV INFUSION Lower serum uric acid in leukemia, lymphoma, or solid malignancies. Adults: 200400 mg/m2/day, to a maximum of 600 mg/day. Children, initial: 200 mg/m2/day. TABLETS Gout/hyperuricemia. Adults: 200300 mg/day for mild gout and 400600 mg/day for moderately severe tophaceous gout, not to exceed 800 mg/day. Minimum effective dose: 100200 mg/day. Prevention of uric acid nephropathy during vigorous treatment of neoplasms. Adults: 600800 mg/day for 23 days (with high fluid intake). Prophylaxis of flare-up of acute gouty attacks. Initial: 100 mg/day; increase by 100 mg at weekly intervals to achieve serum uric acid level of 6 mg/100 mL or less. Hyperuricemia associated with malignancy. Pediatric, 610 years of age: 300 mg/day either as a single dose or 100 mg 3 times per day; under 6 years of age: 150 mg/day in three divided doses. Recurrent calcium oxalate calculi.

termittent). CNS: Agitation, cerebral infarction, coma, dystonia, change in mental status, myoclonus, paralysis, seizures, status epilepticus, tremor, twitching. Hematologic: Leukopenia, eosinophilia, thrombocytopenia, anemia, bone marrow suppression, leukocytosis, DIC, marrow aplasia, neutropenia, pancytopenia. Hepatic: Hepatomegaly, cholestatic jaundice, hepatic necrosis, liver failure, hyperbilirubinemia, jaundice, granulomatous hepatitis. Neurologic: Headache, peripheral neuropathy, paresthesia, somnolence, neuritis. CV: Bradycardia, cardiorespiratory arrest, CV disorder, decreased venous pressure, abnormal ECG, flushing, heart failure, hemorrhage, stroke, hyper-/hypotension, septic shock, ventricular fibrillation, thrombophlebitis, necrotizing angiitis, hypersensitivity vasculitis. GU: Renal failure/insufficiency, hematuria, abnormal kidney function, oliguria, UTI. Respiratory: Apnea, mucositis, pharyngitis, ARDS, respiratory failure, respiratory insufficiency, increased respiratory rate, pulmonary embolus. Metabolic: Abnormal electrolytes, glycosuria, hyper-/hypocalcemia, hyperglycemia, hyper-/hypokalemia, hyper-/hyponatremia, hyperphosphatemia, hyperuricemia, hypomagnesemia, lactic/metabolic acidosis, water intoxication. Miscellaneous: Ecchymosis, headache, blast crisis, edema, cellulitis, chills, diaphoresis, enlarged abdomen, hypervolemia, hypotonia, infection, pain, tumor lysis syndrome, arthralgia, epistaxis, taste loss, acute attacks of gout, fever, myopathy, renal failure, uremia, alopecia. LABORATORY TEST CONSIDERATIONS ALT, AST, alkaline phosphatase, serum cholesterol. Serum glucose. DRUG INTERACTIONS ACE inhibitors / Risk of hypersensitivity reactions Al salts / Allopurinol effect Ampicillin / Risk of drug-induced skin rashes Anticoagulants, oral / Anticoagulant effect R/T liver breakdown Azathioprine / Azathioprine effect R/T liver breakdown
Bold Italic = life threatening side effect

= black box warning

W = Available in Canada

ALLOPURINOL
200300 mg/day in one or more doses (dose may be adjusted according to urinary levels of uric acid). To ameliorate granulocyte suppressant effect of fluorouracil. 600 mg/day. Reduce perioperative mortality and postoperative arrhythmias in coronary artery bypass surgery. 300 mg 12 hr and 1 hr before surgery. Reduce relapse rates of H. pylori-induced duodenal ulcers; treat hematemesis from NSAID-induced erosive gastritis. 50 mg 4 times per day. Alleviate pain due to acute pancreatitis. 50 mg 4 times per day. Treat American cutaneous leishmaniasis and T. cruzi. 20 mg/kg for 15 days. Treat Chagas disease. 600900 mg/day for 60 days. Alternative to treat epileptic seizures refractory to standard therapy. 300 mg/day, except use 150 mg/day in those less than 20 kg. MOUTHWASH Prevent fluorouracil-induced stomatitis. 20 mg in 3% methylcellulose (1 mg/mL compounded in the pharmacy).

NURSING CONSIDERATIONS
E Do not confuse allopurinol with apresoline (an antihypertensive) or Zyloprim with ZORprin (aspirin). ADMINISTRATION/STORAGE 1. Keep urine slightly alkaline to prevent uric acid stone formation. 2. Transfer from colchicine, uricosuric agents, and/or anti-inflammatory agents to allopurinol should be made gradually by decreasing the dosage of one and increasing the dosage of allopurinol until a normal serum uric acid level achieved. 3. Reduce PO dose as follows in impaired renal function: creatinine clearance (CCR) <10 mL/min: 100 mg 3 times per week; CCR 10 mL/min: 100 mg every other day; CCR 20 mL/min: 100 mg/day; CCR 40 mL/min: 150 mg/day; CCR 60 mL/min: 200 mg/day.

4. Do not reuse in those who develop a severe reaction. IV 5. For either adults or children, give daily dose as a single infusion or in equally divided infusions at 6-, 8-, or 12hr intervals at concentration not to exceed 6 mg/mL. 6. Whenever possible, administer 2448 hr before start of chemotherapy known to cause tumor cell lysis (including corticosteroids). 7. Do not mix allopurinol with or administer through the same IV port with agents which are incompatible (see package insert). 8. Dissolve contents of each 30 mL vial with 25 mL of sterile water for injection. Then, dilute to the desired concentration with 0.9% NaCl or D5W injection (do not use sodium bicarbonate-containing solutions); administer over 3060 min. 9. Store reconstituted solution at 2025C (6877F); begin administration within 10 hr after reconstitution. 10. Do not refrigerate either the reconstituted and/or diluted product. ASSESSMENT 1. Take complete drug history; list drugs prescribed that may interact unfavorably. 2. Note reasons for therapy, type, onset of S&S, any previous allopurinol use. List location, severity, and frequency of gout attacks; joint size, swelling, color, deformity, pain and x-ray joint. 3. If female and of childbearing age, or if nursing, avoid allopurinol. 4. Assess for idiopathic hemochromatosis; precludes therapy. 5. Take colchicine with allopurinol for acute flare, especially during first 6 weeks of therapy. 6. Monitor CBC, uric acid, liver and renal function studies. Reduce dose with renal dysfunction. CLIENT/FAMILY TEACHING 1. Take with food or immediately after meals to lessen gastric irritation. Consume at least 1012 8-oz glasses of fluid/day to prevent stone formation. 2. When used IV, ensure sufficient fluid intake to yield a daily urinary output of at least 2 L in adults; maintain neutral,
IV = Intravenous

C = see color insert

H = Herbal

E = sound alike drug

ALLOPURINOL
which include sardines, roe, salmon, scallops, anchovies, organ meats. 10. Gouty attacks may not end for 2 to 6 wk after beginning therapy; take as prescribed. 11. Minimize exposure to UV light due to increased risk of cataracts; report vision changes. 12. Keep F/U visits to evaluate serum/ urinary uric acid levels, response to therapy, and adverse SE. OUTCOMES/EVALUATE Uric acid levels (6 mg/dL)/frequency of gout attacks Joint pain and inflammation Recurrent calcium oxalate renal calculi Hyperuricemia R/T chemo for cancer treatment Prevention of fluorouracil-induced stomatitis/granulocyte suppression (unlabeled)

or preferably, a slightly alkaline urine (pH >7) 3. May cause drowsiness; use caution while driving or performing tasks requiring mental alertness. 4. Monitor weight with N&V or other signs of gastric irritation; report persistent weight loss/gain. 5. Report if rash or flu-like symptoms develop. Skin rashes may start after months of therapy; stop therapy/report to determine if drug-related. 6. Do not take iron salts; high iron concentrations may occur in liver. 7. Avoid excessive intake of vitamin C; may cause kidney stones. 8. Avoid caffeine and excessive intake of alcohol; decreases allopurinol effect. 9. Keep food diary to identify any triggers; may avoid foods high in purine

Bold Italic = life threatening side effect

= black box warning

W = Available in Canada