ZYLOPRIM

What it is

ZYLOPRIM contains allopurinol 100 mg or 300 mg per tablet. Allopurinol inhibits xanthine oxidase, the enzyme which catalyses the conversion of hypoxanthine to xanthine, and of xanthine to urate/uric acid, thereby decreasing urate formation.

Approved indications

— Gouty arthritis, skin tophi and/or renal involvement through crystal deposition or stone formation in idiopathic gout. — Gouty arthritis, skin tophi and/or renal involvement in uric acid lithiasis. — Gouty arthritis, skin tophi and/or renal involvement in acute uric acid nephropathy. — Management of hyperuricaemia secondary to neoplastic disease and myeloproliferative disease with high cell turnover rates, whether occurring spontaneously or after cytotoxic therapy. — Management of hyperuricaemia in certain enzyme disorders which lead to overproduction of urate, including hypoxanthine guanine phosphoribosyltransferase deficiency (including Lesch-Nyhan syndrome), glucose-6-phosphatase deficiency (including glycogen storage disease), phosphoribosylpyrophosphate synthetase deficiency and phosphoribosylpyrophosphate amidotransferase deficiency. — 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

ZYLOPRIM may be taken orally once a day after a meal and is well tolerated, especially after food. Should the daily dosage exceed 300 mg and gastrointestinal intolerance be manifested, a divided dose regimen may be appropriate. 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. Reduced doses should be used in patients with hepatic impairment.

Key safety warnings

ZYLOPRIM should be withdrawn immediately when a skin rash or other evidence of sensitivity occurs. In some instances a skin rash may be followed by more severe hypersensitivity reactions such as exfoliative, urticarial, and purpuric lesions as well as Stevens-Johnson syndrome, 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 Stevens-Johnson syndrome/toxic epidermal necrolysis. The frequency of this 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. ZYLOPRIM 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 ZYLOPRIM, 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. The occurrence of hypersensitivity reactions to allopurinol may be increased in patients with decreased renal function receiving thiazides and ZYLOPRIM concurrently. For this reason, in this clinical setting, such combinations should be administered with caution and patients should be observed closely.

Contraindications

ZYLOPRIM should not be administered in individuals known to be hypersensitive to allopurinol or to any other ingredients of the product. ZYLOPRIM 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. ZYLOPRIM is contraindicated in children with the exception of those with hyperuricaemia secondary to malignancy or with Lesch-Nyhan syndrome, because safety and efficacy have not been established in other conditions.

PBS listing

ZYLOPRIM 300 mg tablets are listed on the PBS with 2 items, restriction type restricted and unrestricted, at an ex-manufacturer price of A$8.74. ZYLOPRIM 100 mg tablets are listed on the PBS with 2 items, restriction type restricted and unrestricted, at an ex-manufacturer price of A$9.75.

Regulatory history

ZYLOPRIM was first listed on the ARTG on 22 February 2017 for both the 300 mg tablet blister pack and 100 mg tablet bottle.