Xanthine oxidase inhibitor
Management of signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy). Management of elevated serum and urinary uric acid levels in patients with leukemia, lymphoma and malignancies receiving cancer therapy. Management of recurrent calcium oxalate calculi with uric acid excretion >800mg/day in males and >750mg/day in females.
Recurrent Calcium Oxalate Calculi
Uric Acid Excretion >800mg/day (Males) and >750mg/day (Females):
200-300mg/day in divided doses or as single equivalent
Titrate: Adjusted up or down depending upon the resultant control of the hyperuricosuria based upon subsequent 24-hr urinary urate determinations
Management of signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)
Moderately Severe Tophaceous Gout:
Reduction of Flare-Up of Acute Gouty Attacks:
Titrate: Increase by 100mg/week until serum uric acid level is ≤6mg/dL
Divide dose if >300mg/day
Uric Acid Nephropathy
Management of elevated serum and urinary uric acid levels in patients w/ leukemia, lymphoma, and malignancies receiving cancer therapy
600-800mg/day for 2-3 days w/ high fluid intake
Divide dose if >300mg/day
Conversion from a Uricosuric Agent:
Gradually reduce dose of uricosuric agent over several weeks while gradually increasing allopurinol to the required dose
Secondary Hyperuricemia with Malignancies
Evaluate response after 48 hrs and adjust dose if necessary
Colchicine/Anti-Inflammatory Agents: While adjusting dose of allopurinol, continue therapy until serum uric acid is normal and no acute gouty attacks occur for months
CrCl 10-20mL/min: 200mg/day
CrCl <3mL/min: Lengthen dosing intervals
Better tolerated if taken following meal
Recommend sufficient fluid intake to yield a daily urinary output of at least 2L; maintain neutral or slightly alkaline urine
Tab: 100mg*, 300mg* *scored
Not for treatment of asymptomatic hyperuricemia. D/C at 1st appearance of skin rash or other signs which indicate an allergic reaction. Hepatotoxicity, elevated serum alkaline phosphatase/transaminase, and bone marrow suppression reported. Monitor LFTs during early stages of therapy with preexisting liver disease. May impair mental/physical abilities. Acute gouty attacks increase during early stages of therapy reported; give colchicine or anti-inflammatory agents. Maintain sufficient fluid intake to yield a daily urinary output of at least 2L and maintain neutral or slightly alkaline urine. Renal failure reported with hyperuricemia secondary to neoplastic diseases; caution with multiple myeloma and congestive myocardial disease. Caution with renal impairment or concurrent illnesses affecting renal function such as HTN and diabetes mellitus (DM); monitor renal function periodically.
Acute gout attacks, rash, diarrhea, SGOT/SGPT increase, alkaline phosphatase increase, nausea.
Inhibits oxidation of mercaptopurine; reduce mercaptopurine or azathioprine to 1/3 or 1/4 of usual dose with concomitant use. Prolongs half-life of dicumarol and chlorpropamide. Decreased effects with uricosuric agents. Increased toxicity with thiazide diuretics; monitor renal function. May increase cyclosporine levels; monitor cyclosporine levels and consider possible adjustment of cyclosporine dose. Increased skin rash with ampicillin and amoxicillin. Enhanced bone marrow suppression with cyclophosphamide and other cytotoxic agents among patients with neoplastic disease, except leukemia.
PREGNANCY AND LACTATION
Category C, caution in nursing.
MECHANISM OF ACTION
Xanthine oxidase inhibitor; acts on purine catabolism; reduces production of uric acid by inhibiting biochemical reactions immediately preceding its formation.
Absorption: Cmax=3mcg/mL (allopurinol), 6.5mcg/mL (oxipurinol); Tmax=1.5 hrs (allopurinol), 4.5 hrs (oxipurinol). Distribution: Found in breast milk. Metabolism: Oxidation; oxipurinol (active metabolite). Elimination: Kidneys, feces (20%); T1/2=1-2 hrs (allopurinol), 15 hrs (oxipurinol).
Assess for renal/hepatic function or preexisting disease, concurrent illnesses affecting renal function (eg, HTN, DM, multiple myeloma, congestive myocardial disease), pregnancy/nursing status, and possible drug interactions. Obtain serum uric acid to provide correct dosage and schedule.
Monitor LFTs, serum uric acid, and renal function periodically. Monitor for signs/symptoms of hepatotoxicity, bone marrow depression, renal dysfunction, hypersensitivity/allergic reaction, and other adverse reactions.
Advise to seek medical attention immediately at 1st sign of skin rash, painful urination, blood in urine, irritation of eyes, or swelling of the lips/mouth. Inform that optimal benefit may be delayed for 2-6 weeks of therapy. Encourage to increase fluid intake during therapy to prevent renal stones. Counsel not to double the dose at the next scheduled time if a dose is missed. Inform about certain risks associated when used concomitantly with other drugs (eg, dicumarol, sulfinpyrazone, mercaptopurine). Inform that drowsiness may occur and physical/mental abilities may be impaired. Instruct to take after meals to minimize gastric irritation.
15-25°C (59-77°F) in dry place. (300mg) Protect from light.
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