Drug Class Description
Enzymes

Generic Name
Rasburicase

Drug Description
After reconstitution, 1 ml of Fasturtec concentrate contains 1.5 mg rasburicase.Fasturtec is a recombinant urate-oxidase enzyme produced by genetically modified Saccharomyces cerevisiae strain. Rasburicase is a tetrameric protein with identical subunits of a molecular mass of about 34 kDa.1 mg corresponds to 18.2 EAU*.*One enzyme activity unit (EAU) corresponds to the enzyme activity that converts 1?mol of uric acid into allantoin per minute under the operating conditions described: +30°C±1°C TEA pH8.9 buffer.

Presentation
Powder and solvent for concentrate for solution for infusion.The powder is an entire or broken white to off white pellet.The solvent is a colourless and clear liquid.

Indications
Treatment and prophylaxis of acute hyperuricaemia, in order to prevent acute renal failure, in patients with haematological malignancy with a high tumour burden and at risk of a rapid tumour lysis or shrinkage at initiation of chemotherapy.

Adult Dosage
Fasturtec should be administered under the supervision of a physician trained in chemotherapy of haematological malignancies.Fasturtec is to be used immediately prior to and during the initiation of chemotherapy only, as at the present, there is insufficient data to recommend multiple treatment courses.The recommended dose for Fasturtec is 0.20 mg/kg/day. Fasturtec is administered as a once daily 30 minute intravenous infusion in 50 ml of a sodium chloride 9 mg/ml (0.9%) solution.The duration of treatment with Fasturtec may be up to 7 days, the exact duration should be based upon adequate monitoring of uric acid levels in plasma and clinical judgment.Administration of rasburicase does not require any change in the timing or schedule of initiation of cytoreductive chemotherapy.Rasburicase solution should be infused over 30 minutes. Rasburicase solution should be infused through a different line than that used for infusion of chemotherapeutic agents to prevent any possible drug incompatibility. If use of a separate line is not possible, the line should be flushed out with saline solution between infusion of chemotherapeutic agents and rasburicase. For instruction on use, see section 6.6.Because rasburicase may degrade uric acid in vitro, special precautions must be used during sample handling for plasma uric acid measurement.Additional information on special populationsRenally or hepatically impaired patients: No dose adjustment is necessary.Paediatric patients: As no dose adjustment is necessary, the recommended dose is 0.20 mg/kg/day

Contra Indications
Hypersensitivity to the active substance or to any of the excipients.G6PD deficiency and other cellular metabolic disorders known to cause haemolytic anaemia. Hydrogen peroxide is a by-product of the conversion of uric acid to allantoin. In order to prevent possible haemolytic anaemia induced by hydrogen peroxide, rasburicase is contraindicated in patients with these disorders.

Special Precautions
Rasburicase like other proteins, has the potential to induce allergic responses in humans. Clinical experience with Fasturtec demonstrates that patients should be closely monitored for the onset of allergic-type undesirable effects, especially severe hypersensitivity reactions including anaphylaxis. In such cases, treatment should immediately and permanently be discontinued and appropriate therapy initiated.Caution should be used in patients with a history of atopic allergies.At present, there is insufficient data available on patients being retreated to recommend multiple treatment courses. Anti-rasburicase antibodies have been detected in treated patients and healthy volunteers administered rasburicase.Methaemoglobinaemia has been reported in patients receiving Fasturtec. Fasturtec should immediately and permanently be discontinued in patients having developed methaemoglobinaemia, and appropriate measures initiated.Haemolysis has been reported in patients receiving Fasturtec. In such case, treatment should immediately and permanently be discontinued and appropriate measures initiated.Administration of Fasturtec reduces the uric acid levels to below normal levels and by this mechanism reduces the chance of development of renal failure due to precipitation of uric acid crystals in renal tubules as a consequence of hyperuricaemia. Tumour lysis can also result in hyperphosphataemia, hyperkalaemia and hypocalcaemia. Fasturtec is not directly effective in the treatment of these abnormalities. Therefore, patients must be monitored closely.Fasturtec has not been investigated in the patients with hyperuricemia in the context of myeloproliferative disorders.There is no data available to recommend the sequential use of Fasturtec and allopurinol.To ensure accurate measurement of uric acid plasma level during treatment with Fasturtec, a strict sample handling procedure must be followed.

Interactions
No metabolism studies have been performed. Rasburicase being an enzyme itself, it would be an unlikely candidate for drug-drug interactions.

Adverse Reactions
Fasturtec is concomitantly administered as supportive care to cytoreductive chemotherapy of advanced malignancies, the causality of adverse events is therefore difficult to assess due to the significant burden of adverse events expected from the underlying disease and its treatment.The most significant drug-related adverse events were common allergic reactions, mainly rashes. Cases of hypotension (< 1%), bronchospasm (< 1%), rhinitis (< 0.1%) and severe hypersensitivity reactions (< 1%), including anaphylaxis (< 0.1%) have also been attributed to Fasturtec.In clinical trials, haematological disorders such as haemolysis, haemolytic anaemia and methaemoglobinaemia are uncommonly caused by Fasturtec. The enzymatic digestion of uric acid to allantoin by rasburicase produces hydrogen peroxide and haemolytic anaemia or methaemoglobinaemia have been observed in certain at risk populations such as those with G6PD deficiency.In addition, grade 3 or 4 adverse reactions possibly attributable to Fasturtec and reported in the clinical trials, are listed below, by system organ class and by frequency. Frequencies are defined as: common (1/100, <1/10), uncommon ( 1/1,000, <1/100).CommonUncommonNervous system disordersHeadacheGastrointestinal disordersDiarrhoea Vomiting NauseaGeneral disorders and administration site conditionsFeverWithin each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Manufacturer
sanofi-aventis

Drug Availability
(POM)

Updated
21 September 2009