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Indian Journal of Pharmacology, Vol. 36, No. 2, April, 2004, pp. 109 Molecules of the Millennium Rasburicase Sharma G, Verma I Department of Pharmacology, Govt. Medical College, Amritsar - 143 001 Code Number: ph04043 Rasburicase is a genetically engineered, recombinant form of urate oxidase enzyme that has recently been approved for use both in the United States and Europe, for the treatment and prophylaxis of hyperuricaemia associated with tumor lysis syndrome in pediatric patients. Rasburicase is made up of a single polypeptide chain with 301 amino acids and is produced from Saccharomyces cerevisiae. Hyperuricaemia is a component of ′tumor lysis syndrome′ which is a condition that occurs when patients with a high tumor burden (leukemias, lymphomas and solid tumor malignancies) are given chemotherapy. This secondary increase in uric acid levels can lead to acute renal failure which is a severe and potentially life-threatening condition. The condition has been conventionally managed by giving the patient plenty of fluids, alkalization of urine and administration of allopurinol which may occasionally lead to an overload of uric acid precursors and cause xanthine nephropathy. Rasburicase presents a new approach for managing secondary hyperuricaemia. Urate oxidase is an enzyme lacking in humans, but present normally in other mammals. It is responsible for rapidly converting the poorly soluble uric acid to highly soluble allantoin which is easily excreted by the kidneys. Rasburicase is administered just before the start of chemotherapy. It is given as an IV infusion over a period of 30 minutes, in a dose of 0.15 - 0.2 mg/kg body weight, daily for 5 days. Chemotherapy is initiated 4-24 hours after the first dose of rasburicase. The lyophilized product and the diluent have to be stored at 2-8°C. The drug has a half-life of 19 hours and is metabolized by hydrolysis. In clinical trials which compared rasburicase to allopurinol, the former reduced the concentration of uric acid significantly faster than allopurinol. Attributable adverse effects seen with rasburicase were hypersensitivity reactions ranging from rashes, bronchospasm and hypotension to severe anaphylaxis. Other Grade 3 or 4 adverse events included fever, nausea, vomiting, diarrhea and headache. Rasburicase, being a protein, may stimulate the formation of antibodies against itself; it is also associated with methaemoglobinaemia. In patients with G-6PD deficiency, this drug can cause severe hemolysis. The drug has only been approved for a single course of treatment. Further immunogenicity studies are underway to determine the impact of antibody formation and settle the issue of repeated use of rasburicase. Sources http://www.fda.gov/cber/label/rasbsan071202LB.pdfhttp://www.docguide.com/news/content.nsf/news/8525697700573E1885256BF90060D9F3 Copyright 2004 - Indian Journal of Pharmacology |
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