oh PURE i
Allopurinol Sodium Injection|
Xanthine Oxidase Inhibitor
Oral: Prevention of attack of gouty arthritis and nephropathy; also used to
treat secondary hyperuricemia which may occur during treatment of tumors or
leukemia, and to prevent recurrent calcium oxalate calculi
Intravenous: Management of patients with leukemia, lymphoma, and solid tumor
malignancies who are receiving cancer chemotherapy which causes elevations of
serum and urinary uric acid levels and who cannot tolerate oral therapy
Clinical effects on the fetus: There are few reports describing the use of
allopurinol during pregnancy; no adverse fetal outcomes attributable to
allopurinol have been reported in humans
Not to be used in pregnancy or lactation, or in patients with a previous
severe allergy reaction to allopurinol or any component
Do not use to treat asymptomatic hyperuricemia. Discontinue at first signs of
rash; reduce dosage in renal insufficiency, reinstate with caution in patients
who have had a previous mild allergic reaction, use with caution in children;
monitor liver function and complete blood counts before initiating therapy and
periodically during therapy, use with caution in patients taking diuretics
concurrently. Risk of skin rash may be increased in patients receiving
amoxicillin or ampicillin. The risk of hypersensitivity may be increased in
patients receiving thiazides, and possibly ACE inhibitors.
The most common adverse reaction to allopurinol is a skin rash (usually
maculopapular; however, more severe reactions, including Stevens-Johnson
syndrome, have also been reported). While some studies cite an incidence of
these reactions as high as >10% of cases (often in association with
ampicillin or amoxicillin), the product labeling cites a much lower incidence,
reflected below. Allopurinol should be discontinued at the first appearance of a
rash or other sign of hypersensitivity.
Dermatologic: Rash (1.5%)
Gastrointestinal: Nausea (1.3%), vomiting (1.2%)
Renal: Renal failure/impairment (1.2%)
<1%: Hypersensitivity syndrome, increased alkaline phosphatase or hepatic
transaminases, granulomatous hepatitis, dyspepsia, pancreatitis, gynecomastia,
agranulocytosis, aplastic anemia, acute tubular necrosis, interstitial
nephritis, nephrolithiasis, vasculitis, TEN, exfoliative dermatitis,
Stevens-Johnson syndrome, granuloma annulare, toxic pustuloderma, peripheral
neuropathy, neuritis, paresthesia, bronchospasm, cataracts, macular retinitis,
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
Hepatic enzyme inhibitor
Inhibits metabolism of azathioprine and mercaptopurine (reduce to 1/3 or 1/4
of usual dose)
Use with ampicillin or amoxicillin may increase the incidence of skin rash
Urinary acidification with large amounts of vitamin C may increase kidney
Thiazide diuretics enhance toxicity, monitor renal function; thiazide
diuretics and captopril (possibly other ACE inhibitors) may increase risk of
Vidarabine neurotoxicity may be enhanced
Cyclosporine levels may be increased
Hepatic iron uptake may be increased with iron supplements
Allopurinol prolongs half-life of oral anticoagulants; allopurinol increases
serum half-life of theophylline; allopurinol may compete for excretion in renal
tubule with chlorpropamide and increases chlorpropamide's serum half-life
Store intact vials of unreconstituted powder at 15°C to
30°C (59°F to
86°F). Allopurinol sodium for injection should be
dissolved with 25 mL of sterile water for injection. Reconstitution should yield
a clear, almost colorless solution with no more than a slight opalescence. The
initial solution should be diluted to the desired concentration with 0.9% sodium
chloride injection or 5% dextrose for injection. Sodium
bicarbonate-containing solutions should not be used. A final concentration
of no greater than 6 mg/mL is recommended. The solution should be stored at
20°C to 25°C
(68°F to 77°F) and administration
should begin within 10 hours after reconstitution. Do not refrigerate the
reconstituted and/or diluted product.
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.
Decreases in serum uric acid occur in 1-2 days with nadir achieved in 1-2
Oral: ~80% of dose absorbed from GI tract; peak plasma concentrations are
seen 30-120 minutes after administration
Rectal: Poor and erratic
Distribution: Vd~1.6 L/kg; Vss: 0.84-0.87 L/kg;
distributes into breast milk
Protein binding: <1%
Metabolism: ~75% metabolized to active metabolites, chiefly oxypurinol
Bioavailability: 49% to 53%
Normal renal function:
Parent drug: 1-3 hours
Oxypurinol: 18-30 hours
End-stage renal disease: Half-life is prolonged
Elimination: Both allopurinol and oxypurinol are dialyzable; 10% may be
eliminated by enterohepatic excretion; excreted in urine, 76% as oxypurinol, 12%
as unchanged allopurinol
Children less than or equal to 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
Alternative: <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: Daily doses >300 mg should be
administered in divided doses
Myeloproliferative neoplastic disorders: 600-800 mg/day in 2-3 divided doses
for prevention of acute uric acid nephropathy for 2-3 days starting 1-2 days
Gout: Mild: 200-300 mg/day; Severe: 400-600 mg/day
Elderly: Initial: 100 mg/day, increase until desired uric acid level is
Dosing adjustment in renal impairment: Must be adjusted due to
accumulation of allopurinol and metabolites; removed by hemodialysis. Adult
maintenance doses of allopurinol* (mg) based on creatinine clearance
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
*Doses based on a standard maintenance dose of 300 mg of allopurinol per day
for a patient with a creatinine clearance of 100 mL/minute.
Hemodialysis: Administer dose posthemodialysis or administer 50% supplemental
I.V.: 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: Starting dose: 200 mg/m2/day
Adults: 200-400 mg/m2/day (max: 600 mg/day)
Dosing adjustment in renal impairment: 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
Should be administered after meals with plenty of fluid
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 at the recommended final concentration of less
than or equal to 6 mg/mL.
CBC, serum uric acid levels, I & O, hepatic and renal function,
especially at start of therapy
Uric acid, serum: An increase occurs during childhood
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.
|Mental Health: Effects
on Mental Status|
May cause drowsiness
Effects on Psychiatric
Rarely may cause bone marrow suppression; use caution with clozapine and
|Dental Health: Local
No information available to require special precautions
Effects on Dental Treatment|
No effects or complications reported
Take as directed. Maintain adequate hydration (2-3 L/day of fluids unless
instructed to restrict fluid intake) to avoid possible adverse renal problems.
While using this medication, do not use alcohol, other prescription or OTC
medications, or vitamin substances 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); 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 precautions: Inform prescriber if you
are or intend to be pregnant.
Monitor CBC, serum uric acid levels, I & O, hepatic and renal function,
especially at start of therapy
Injection: 500 mg
Tablet: 100 mg, 300 mg
Crush tablets to make a 5 mg/mL suspension in simple syrup; stable 14 days
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.
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,
Emmerson BT, "The Management of Gout," N Engl J Med, 1996,
Ferner RE, Simmonds HA, and Bateman DN,
"Allopurinol Kinetics After Massive Overdose," Hum Toxicol, 1988,
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,
Copyright © 1978-2000 Lexi-Comp Inc. All Rights Reserved