FASTURTEC Powder and solvent for concentrate for solution for infusion Ref.[8536] Active ingredients: Rasburicase

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.

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.

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

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.

No studies on the effects on the ability to drive and use machines have been performed.

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 diarrhea.

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 available data).

Tabulated list of adverse reactions:

* Anaphylactic shock including potential fatal outcome
** From post-marketing experience
⁺ Uncommon G3/4
⁺⁺ Common G3/4

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

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 chemotherapeutic agent infusions and rasburicase.

No filter should be used for infusion.

Do not use any glucose solution for dilution due to potential incompatibility.