Leitlinien & Arzneimittelsicherheit

HOS-084364 · has-adverse-reaction-information · PDF-Seite 4

Summary of the safety profile 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 commonly reported adverse reactions were nausea, vomiting, headache, fever, and diarrhoea. 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. 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 using the following MedDRA convention as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the 4 available data). Tabulated list of adverse reactions MedDRA Very Common Uncommon Rare Not known Organ system common classes Blood and - Haemolysis lymphatic - Haemolytic system anaemia disorders - Methaemoglobin aemia Immune - Allergy/ - Severe - Anaphylaxis - Anaphylactic system allergic hypersensitivity shock* disorders reactions reactions (rashes and urticaria) Nervous system - Headache + - Convulsion** - Muscle disorders contraction involuntary** Vascular

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HOS-084360 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 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.

HOS-084359 · has-indication-information · PDF-Seite 2

Treatment and prophylaxis of acute hyperuricaemia, in order to prevent acute renal failure, in adults, children and adolescents (aged 0 to 17 years) with haematological malignancy with a high tumour burden and at risk of a rapid tumour lysis or shrinkage at initiation of chemotherapy.

HOS-084362 · has-interaction-information · PDF-Seite 4

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

HOS-084363 · has-pregnancy-information · PDF-Seite 4

Pregnancy There are no data from the use of rasburicase in pregnant women. Results from animal studies could not be interpreted due to the presence of endogenous urate oxidase in standard animal models. Because teratogenic effects of rasburicase cannot be ruled out, Fasturtec should only be used during pregnancy if strictly necessary. Fasturtec is not recommended in women of childbearing potential not using contraception. Breast-feeding It is unknown whether rasburicase is excreted in human milk. As a protein the dose for the infant is expected to be very low. During treatment with Fasturtec, the advantage of breastfeeding should be weighted against the potential risk for the infant. Fertility There are no data regarding the effect of rasburicase on fertility.

HOS-084361 · has-warning-information · PDF-Seite 3

Rasburicase like other proteins, has the potential to induce allergic responses in humans, such as anaphylaxis, including anaphylactic shock, with potential fatal outcome. 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 (see section 4.8). In case of severe allergic reaction, 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 (see section 4.8). Haemolysis has been reported in patients receiving Fasturtec. In such case, treatment should immediately and permanently be discontinued and appropriate measures initiated (see section 4.8). 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. 3 To ensure accurate measurement of uric acid plasma level during treatment with Fasturtec, a strict sample handling procedure must be followed (see section 6.6). This medicinal product contains up to 10.5 mg sodium per vial, equivalent to 0.53 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.