Allopurinol

Allopurinol tablet is indicated for: The management of adults with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy) The management of adult and pediatric patients with leukemia, lymphoma and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels The management of adult patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients, despite lifestyle changes (such as reduction of dietary sodium, non-dairy animal protein, oxylate rich foods, refined sugars and increases in oral fluids and fruits and vegetables) Limitations of Use Allopurinol tablet is not recommended for the treatment of asymptomatic hyperuricemia.

Allopurinol is a structural analogue of the natural purine base, hypoxanthine. Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in humans. Allopurinol is metabolized to the corresponding xanthine analogue, oxypurinol (alloxanthine), which also is an inhibitor of xanthine oxidase.

Gout: Prior to initiating treatment assess serum uric acid level, complete blood count, chemistry panel, liver and kidney function tests. Prophylactic treatment for gout flares is recommended. Patients with normal kidney function: Initial dosage is 100 mg orally daily. Increase by 100 mg weekly increments until serum uric acid of 6 mg/dl or less is reached (maximum 800 mg daily). Patients with impaired kidney function: The initial dosage is 50 mg orally daily. Follow recommendations for titration in patients with renal impairment until target serum uric acid level is reached. See complete information in the Full Prescribing Information (FPI). Hyperuricemia Associated with Cancer Therapy: The recommended dosage is: Adults: 300 mg to 800 mg orally daily. Pediatric patients: 100 mg/m 2 orally every 8 hours to 12 hours (10 mg/kg/day, maximum 800 mg/day) See complete information in the FPI.

Allopurinol tablet is contraindicated in patients with a history of hypersensitivity reaction to allopurinol or to any of the ingredients of allopurinol tablets. Known hypersensitivity to allopurinol or to any of the ingredients of allopurinol tablets.

Skin Rash and Hypersensitivity: Allopurinol has been associated with serious and sometimes fatal dermatological reactions. Discontinue allopurinol tablets at the first appearance of skin rash or other signs of hypersensitivity reaction. Gout Flares: May occur during initiation of treatment. Concurrent prophylactic treatment with colchicine or anti-inflammatory agents is recommended. Nephrotoxicity: Allopurinol may affect kidney function. Patients with decreased kidney function require lower doses of allopurinol tablets. Hepatoxicity: Cases of reversible hepatotoxicity have occurred. If signs and symptoms of hepatotoxicity develop, evaluate liver function. Myelosuppression: Bone marrow suppression has been reported with allopurinol. Potential Effect on Driving and Use of Machinery: Drowsiness, somnolence and dizziness have been reported in patients taking allopurinol tablets.

The following clinically significant adverse reactions are described elsewhere in the labeling: Skin Rash and Hypersensitivity Nephrotoxicity Hepatoxicity Myelosuppression Potential Effect on Driving and Use of Machinery The following adverse reactions associated with the use of allopurinol were identified in literature, unpublished clinical trials or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most frequent adverse reaction to allopurinol is skin rash. Most Common Adverse Reactions (≥ 1%) Gastrointestinal: Diarrhea, nausea, alkaline phosphatase increase, AST/ALT increase. Metabolic and Nutritional: Acute attacks of gout. Skin and Appendages: Rash, maculopapular rash.

The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. Capecitabine: Avoid concomitant use. Mercaptopurine or Azathioprine: Reduce mercaptopurine or azathioprine dose as recommended in the respective prescribing information. Pegloticase: Discontinue and refrain from initiating treatment with allopurinol tablets. See FPI for complete list of significant drug interactions.

Store at 20°C to 25°C (USP Controlled Room Temperature) (68°F to 77°F) in a dry place.