Overview
11 DESCRIPTION Allopurinol, USP is a xanthine oxidase inhibitor. It has the following structural formula: Allopurinol, USP is known chemically as 1, 5-dihydro-4 H -pyrazolo [3, 4- d ]pyrimidin-4-one and it has a molecular weight of 136.1 g/mol. Soluble in solutions of potassium and sodium hydroxides, very slightly soluble in water and in alcohol; practically insoluble in chloroform and in ether.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Allopurinol tablets are 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. 12.
Indications
- 1 INDICATIONS AND USAGE Allopurinol tablets are 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,...
Common Doses
- 100 mg
- 6 mg
- 800 mg
- 50 mg
Dosage
2 DOSAGE AND ADMINISTRATION 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. ( 2.1 , 2.2 ) 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). ( 2.3 ) Patients with impaired kidney function: The initial dosage is 50 mg orally daily.
Black Box Warning
BOXED WARNING
Contraindications
- 4 CONTRAINDICATIONS Allopurinol tablets are 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.
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Skin Rash and Hypersensitivity [see Warnings and Precautions ( 5.1 )] Nephrotoxicity [see Warnings and Precautions ( 5.3 )] Hepatoxicity [see Warnings and Precautions ( 5.4 )] Myelosuppression [see Warnings and Precautions ( 5.5 )] Potential Effect on Driving and Use of Machinery [see Warnings and Precautions ( 5.6 )] The following adverse reactions associated with the use of allopurinol tablets were identified in literature, unpublished clinical trials or postmarketing reports.
Interactions
- 7 DRUG INTERACTIONS The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) Capecitabine: Avoid concomitant use. ( 7.2 ) Mercaptopurine or Azathioprine: Reduce mercaptopurine or azathioprine dose as recommended in the respective prescribing information. ( 7.2 ) Pegloticase: Discontinue and refrain from initiating treatment with allopurinol tablets. ( 7.2 ) See FPI for complete list of significant drug interactions. ( 7.2 ) 7.