Drugs List

Therapeutic Indications

Uses

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.

Administration

The solution should be infused intravenously over 30 minutes. It is to be used immediately before and during the initiation of chemotherapy only, as at the present, there is insufficient data to recommend multiple treatment courses.

Administration of rasburicase does not require any change in the timing or schedule of initiation of cytoreductive chemotherapy.

The solution should be infused through a different line from 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.

Handling

Rasburicase must be reconstituted with the solvent supplied and further diluted in 0.9% w/v sodium chloride intravenous solution.

It is recommended that the reconstituted and diluted solution is used immediately, but stability has been demonstrated for 24 hours at 2 to 8 degrees C.

Reconstitution

Add the content of one ampoule of solvent to one vial containing rasburicase and mix by swirling very gently under controlled and validated aseptic conditions. Do not shake. Inspect visually prior to use. Only clear and colourless solutions without particles should be used.
After reconstitution 1ml contains 1.5mg rasburicase.
For single-use only, any unused solution should be discarded.
The solvent contains no preservative and, therefore, the reconstituted solution should be diluted under controlled and validated aseptic conditions.

Dilution before infusion:
The required volume of the reconstituted solution (according to the patient's body weight) is to be further diluted with 0.9% w/v sodium chloride intravenous solution to make up a total volume of 50ml. The final concentration of this solution will vary, depending on the patient's bodyweight.

The reconstituted solution contains no preservative and therefore should be infused immediately.

Incompatibilities

This product should not be mixed with other medicinal products. Rasburicase solution should be infused through a different line from 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 0.9% w/v sodium chloride solution between infusion of chemotherapeutic agents and rasburicase. No filter should be used for infusion.

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

Contraindications

Rasburicase facilitates the oxidation of uric acid to allantoin. Hydrogen peroxide is a by-product of this reaction and in order to prevent hydrogen peroxide-induced haemolytic anaemia, rasburicase should not be used in patients with:
G6PD deficiency
Metabolic disorders known to cause haemolytic anaemia.

Pregnancy - see 'Pregnancy' section
Breastfeeding - see 'Lactation' section

Precautions and Warnings

Rasburicase, like other proteins, has the potential to induce allergic responses in humans. Patients should be closely monitored for the onset of allergic-type undesirable effects, especially severe hypersensitivity reactions ( rash, bronchospasm ) including anaphylaxis. If any serious allergic or anaphylactic reaction occurs, treatment should be discontinued immediately 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 noted as a side effect in patients receiving rasburicase. If methaemoglobinaemia does occur, rasburicase should be immediately and permanently discontinued, and appropriate measures initiated.

Haemolysis has been noted as a side effect in patients receiving rasburicase. If haemolysis does occur, rasburicase should be immediately and permanently discontinued, and appropriate measures initiated.

Administration of rasburicase reduces the uric acid levels to below normal levels and by this mechanism reduces the possibility of developing renal failure due to the precipitation of uric acid crystals in renal tubules as a consequence of hyperuricaemia. Tumour lysis can also result in hyperphosphataemia, hyperkalaemia and hypocalcaemia. Rasburicase is not directly effective in these abnormalities. Therefore, patients must be monitored closely.

Rasburicase has not been investigated in the patients with hyperuricaemia in the context of myeloproliferative disorders.

There is no data available to recommend the sequential use of rasburicase and allopurinol.

Special precautions must be used during sample handling to ensure accurate measurement of uric acid plasma level during treatment because rasburicase may degrade uric acid in vitro . If it is necessary to monitor a patient's uric acid level, a strict sample-handling procedure must be followed to minimise ex vivo degradation of the analyte. Blood must be collected into pre-chilled tubes containing heparin anticoagulant. Samples must be immersed in an ice/water bath. Plasma samples should immediately be prepared by centrifugation in a pre-cooled centrifuge (4 degrees C). Finally, plasma must be maintained in an ice/water bath and analysed for uric acid within 4 hours.

Pregnancy and Lactation

Pregnancy

Rasburicase should not be used during pregnancy.

No clinical data on exposed pregnancies are available and the potential risk for humans is unknown. Animal studies with respect to effects on pregnancy, embryonic/foetal development, parturition and postnatal development have not been performed.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Rasburicase should not be used by breastfeeding women.

It is unknown whether rasburicase is excreted in human breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Allergic reactions
Rash
Hypotension
Bronchospasm
Rhinitis
Hypersensitivity reactions
Anaphylaxis
Haemolysis
Methaemoglobinaemia
Haemolytic anaemia
Vomiting
Nausea
Diarrhoea
Headache
Fever
Urticaria

Presentation

Powder containing 1.5mg rasburicase per vial plus solvent for concentrate for solution for infusion.
Powder containing 7.5mg rasburicase per vial plus solvent for concentrate for solution for infusion.

After reconstitution one ml contains 1.5mg rasburicase

Drugs List

Therapeutic Indications

Uses

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.

Dosage

Administration should be under the supervision of a physician trained in chemotherapy of haematological malignancies.

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

The solution should be infused intravenously over 30 minutes. It is to be used immediately before and during the initiation of chemotherapy only, as at the present, there is insufficient data to recommend multiple treatment courses.

Administration of rasburicase does not require any change in the timing or schedule of initiation of cytoreductive chemotherapy.

The solution should be infused through a different line from 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.

Handling

Rasburicase must be reconstituted with the solvent supplied and further diluted in 0.9% w/v sodium chloride intravenous solution.

It is recommended that the reconstituted and diluted solution is used immediately, but stability has been demonstrated for 24 hours at 2 to 8 degrees C.

Reconstitution

Add the content of one ampoule of solvent to one vial containing rasburicase and mix by swirling very gently under controlled and validated aseptic conditions. Do not shake. Inspect visually prior to use. Only clear and colourless solutions without particles should be used.
After reconstitution 1ml contains 1.5mg rasburicase.
For single-use only, any unused solution should be discarded.
The solvent contains no preservative and, therefore, the reconstituted solution should be diluted under controlled and validated aseptic conditions.

Dilution before infusion:
The required volume of the reconstituted solution (according to the patient's body weight) is to be further diluted with 0.9% w/v sodium chloride intravenous solution to make up a total volume of 50ml. The final concentration of this solution will vary, depending on the patient's bodyweight.

The reconstituted solution contains no preservative and therefore should be infused immediately.

Incompatibilities

This product should not be mixed with other medicinal products. Rasburicase solution should be infused through a different line from 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 0.9% w/v sodium chloride solution between infusion of chemotherapeutic agents and rasburicase. No filter should be used for infusion.

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

Contraindications

Rasburicase facilitates the oxidation of uric acid to allantoin. Hydrogen peroxide is a by-product of this reaction and in order to prevent hydrogen peroxide-induced haemolytic anaemia, rasburicase should not be used in patients with:
G6PD deficiency
Metabolic disorders known to cause haemolytic anaemia.

Pregnancy - see 'Pregnancy' section
Breastfeeding - see 'Lactation' section

Precautions and Warnings

Rasburicase, like other proteins, has the potential to induce allergic responses in humans. Patients should be closely monitored for the onset of allergic-type undesirable effects, especially severe hypersensitivity reactions ( rash, bronchospasm ) including anaphylaxis. If any serious allergic or anaphylactic reaction occurs, treatment should be discontinued immediately 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 noted as a side effect in patients receiving rasburicase. If methaemoglobinaemia does occur, rasburicase should be immediately and permanently discontinued, and appropriate measures initiated.

Haemolysis has been noted as a side effect in patients receiving rasburicase. If haemolysis does occur, rasburicase should be immediately and permanently discontinued, and appropriate measures initiated.

Administration of rasburicase reduces the uric acid levels to below normal levels and by this mechanism reduces the possibility of developing renal failure due to the precipitation of uric acid crystals in renal tubules as a consequence of hyperuricaemia. Tumour lysis can also result in hyperphosphataemia, hyperkalaemia and hypocalcaemia. Rasburicase is not directly effective in these abnormalities. Therefore, patients must be monitored closely.

Rasburicase has not been investigated in the patients with hyperuricaemia in the context of myeloproliferative disorders.

There is no data available to recommend the sequential use of rasburicase and allopurinol.

Special precautions must be used during sample handling to ensure accurate measurement of uric acid plasma level during treatment because rasburicase may degrade uric acid in vitro . If it is necessary to monitor a patient's uric acid level, a strict sample-handling procedure must be followed to minimise ex vivo degradation of the analyte. Blood must be collected into pre-chilled tubes containing heparin anticoagulant. Samples must be immersed in an ice/water bath. Plasma samples should immediately be prepared by centrifugation in a pre-cooled centrifuge (4 degrees C). Finally, plasma must be maintained in an ice/water bath and analysed for uric acid within 4 hours.

Pregnancy and Lactation

Pregnancy

Rasburicase should not be used during pregnancy.

No clinical data on exposed pregnancies are available and the potential risk for humans is unknown. Animal studies with respect to effects on pregnancy, embryonic/foetal development, parturition and postnatal development have not been performed.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Rasburicase should not be used by breastfeeding women.

It is unknown whether rasburicase is excreted in human breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

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

Side Effects

Allergic reactions
Rash
Hypotension
Bronchospasm
Rhinitis
Hypersensitivity reactions
Anaphylaxis
Haemolysis
Methaemoglobinaemia
Haemolytic anaemia
Vomiting
Nausea
Diarrhoea
Headache
Fever
Urticaria

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store at 2 to 8 degrees C.
Do not freeze.
Store in the original package to protect from light.

Further Information

Last Full Review Date: February 2012

Reference Sources

Summary of Product Characteristics: Fasturtec. Sanofi-Aventis. Revised February 2009.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 06 September 2017