ALLOPURINOL

What it is

ALLOPURINOL-WGR is available in 100 mg and 300 mg tablet formulations. Allopurinol inhibits xanthine oxidase, the enzyme which catalyses the conversion of hypoxanthine to xanthine, and of xanthine to urate/uric acid. Allopurinol decreases urate formation and reduces urate/uric acid concentrations in both body fluids and urine.

Approved indications

— Gouty arthritis, skin tophi and/or renal involvement through crystal deposition or stone formation due to main clinical manifestations of urate/uric acid deposition. — Idiopathic gout. — Uric acid lithiasis. — Acute uric acid nephropathy. — Neoplastic disease and myeloproliferative disease with high cell turnover rates where high urate levels occur either spontaneously or after cytotoxic therapy. — Certain enzyme disorders which lead to overproduction of urate, including hypoxanthine guanine phosphoribosyltransferase (including Lesch-Nyhan syndrome), glucose 6-phosphatase (including glycogen storage disease), phosphoribosylpyrophosphate synthetase, and phosphoribosylpyrophosphate amidotransferase. — Management of 2,8-dihydroxyadenine (2,8-DHA) renal stones related to deficient activity of adenine phosphoribosyl transferase. — Management of recurrent mixed calcium oxalate renal stones in the presence of hyperuricosuria, when fluid, dietary and similar measures have failed.

Dosing overview

The dosage should be adjusted by monitoring serum urate concentrations and urinary urate/uric acid levels at appropriate intervals. Allopurinol may be taken orally once a day after a meal. Should the daily dosage exceed 300 mg and gastrointestinal intolerance be manifested, a divided dose regimen may be appropriate. In the elderly, in the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used. In the presence of impaired renal function, serious consideration should be given to initiating treatment with a maximum dose of 100 mg/day and increasing it only if the serum and/or urinary urate response is unsatisfactory.

Key safety warnings

Allopurinol should be withdrawn immediately when a skin rash or other evidence of sensitivity occurs, and should be discontinued at the first appearance of skin rash or other signs which may indicate an allergic reaction. Skin rash may be followed by more severe hypersensitivity reactions such as exfoliative, urticarial, and purpuric lesions as well as Stevens-Johnson syndrome (erythema multiforme exudativum), drug rash with eosinophilia and systemic symptoms (DRESS), Lyell's disease, generalised vasculitis, irreversible hepatotoxicity, and on rare occasions death. The HLA-B*5801 allele has been shown to be associated with the risk of developing allopurinol related hypersensitivity syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), with frequencies varying widely between ethnic populations (up to 20% in Han Chinese, 8–15% in Thai, about 12% in Korean, and 1–2% in Japanese or European populations), and screening for HLA-B*5801 should be considered before starting treatment with allopurinol in patient subgroups where the prevalence of this allele is known to be high. Allopurinol treatment should not be started until an acute attack of gout has completely subsided as further attacks may be precipitated, and in the early stages of treatment an acute attack of gouty arthritis may be precipitated, so prophylaxis with a suitable anti-inflammatory agent or colchicine (0.5 mg three times a day) is advisable for at least one month. The occurrence of hypersensitivity reactions to allopurinol may be increased in patients with decreased renal function receiving thiazides and allopurinol concurrently, and such combinations should be administered with caution with patients observed closely.

Contraindications

Allopurinol should not be administered to individuals known to be hypersensitive to allopurinol or to any other components of the formulation. Allopurinol should not be given concomitantly with iron salts to patients with idiopathic haemochromatosis, nor should it be given to the immediate relatives of such patients. Allopurinol is contraindicated in children with the exception of those with hyperuricemia secondary to malignancy or with Lesch-Nyhan syndrome, because safety and efficacy have not been established in other conditions.

Regulatory history

ALLOPURINOL-WGR received initial approval on 22 February 2017. Earlier ALLOPURINOL ALPHAPHARM registrations were first listed on 1991-09-20 for the 300 mg formulation and 1991-10-21 for the 100 mg formulation.