Allopurinol-WGR

What it is

Allopurinol-WGR is available as 100 mg and 300 mg tablets. 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 in the context of 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, in which 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

Allopurinol may be taken orally once a day after a meal. For adults, the dose ranges from 100 to 200 mg daily in mild conditions; 300 to 600 mg daily in moderately severe conditions; and 700 to 900 mg daily in severe conditions, or alternatively 2 to 10 mg/kg bodyweight/day. The dosage should be adjusted by monitoring serum urate concentrations and urinary urate/uric acid levels at appropriate intervals. 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 discontinued at the first appearance of skin rash or other signs which may indicate an allergic reaction. A skin rash may be followed by more severe hypersensitivity reactions such as exfoliative, urticarial, and purpuric lesions as well as Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), Lyell's syndrome, 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 SJS/TEN. The frequency of the HLA-B*5801 allele varies widely between ethnic populations: up to 20% in Han Chinese population, 8–15% in the Thai population, about 12% in the Korean population and 1–2% in individuals of Japanese or European origin. Screening for HLA-B*5801 should be considered before starting treatment 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. In the early stages of treatment with allopurinol, an acute attack of gouty arthritis may be precipitated. Therefore it is advisable to give prophylaxis with a suitable anti-inflammatory agent or colchicine (0.5 mg three times a day) for at least one month. Bone marrow depression has been reported in patients receiving allopurinol, most of whom received concomitant medicines with the potential for causing this reaction. This has occurred as early as six weeks to as long as six years after the initiation of therapy. Rarely a patient may develop varying degrees of bone marrow depression, affecting one or more cell lines, while receiving allopurinol alone.

Contraindications

Allopurinol should not be administered in individuals known to be hypersensitive to allopurinol or to any other ingredients of the product. 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 100 mg and 300 mg tablets were first listed on the ARTG on 22 February 2017 under licence category RE (register of established medicines).