Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Fasturtec (Sanofi-Synthelabo)

glass vials containing 1.5 mg freeze-dried powder
Approved indication: treatment and prophylaxis of acute hyperuricaemia
Australian Medicines Handbook section 15.3

Rapidly proliferating tumours increase the production of uric acid. If the tumour cells are damaged by chemotherapy the resulting hyperuricaemia can cause acute renal failure.

Humans lack the enzyme (urate oxidase) which, in other mammals, converts uric acid to a more soluble molecule. A genetically engineered form of the enzyme(rasburicase) has been developed. This can be used when there is a risk of rapid tumourlysis in a patient with a haematological malignancy.

Rasburicase is infused when the patient starts chemotherapy. The daily infusion is given over 30 minutes for 5-7 days. Ideally, it should not be given through the same line as the patient's chemotherapy. The half-life of rasburicase is approximately 19 hours and like other proteins it is broken down by hydrolysis.

Allopurinol (which reduces uric acid production by inhibiting xanthine oxidase)can be used as prophylaxis against hyperuricaemia. An open-label randomized trial has therefore compared rasburicase to oral allopurinol in 52 children starting chemotherapy for leukaemia or lymphoma. Rasburicase reduced the concentration of uric acid significantly faster than allopurinol during the first four days of chemotherapy. Uric acid concentrations fell by 86% within four hours of a dose of rasburicase, compared to 12% after allopurinol. This more rapid reduction resulted in patients having 2.6 times less exposure to uric acid in the first four days of therapy.1

Attributing adverse effects, such as fever, nausea and vomiting, to rasburicase in patients receiving chemotherapy can be difficult. There is a problem inpatients with a deficiency of glucose-6-phosphate dehydrogenase as the oxidation of uric acid may precipitate a haemolytic anaemia. As rasburicase is a protein it has the potential to cause allergic reactions. Some patients will develop antibodies to rasburicase.

Clinical experience with rasburicase is limited and it is not approved for use in subsequent courses of chemotherapy. An intravenous drug may be expected to have a more rapid effect than an oral drug so some caution is needed when interpreting the comparative study. This study was also too small to show any significant differences in renal failure or the need for dialysis.1


References

  1. Goldman SC, Holcenberg JS, Finklestein JZ, Hutchinson R, Kreissman S, Johnson FL, et al. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumorlysis. Blood 2001;97:2998-3003.