Drugs List

Therapeutic Indications

Uses

Leukaemia - acute lymphoblastic

Treatment of acute lymphoblastic leukaemia in combination with other anti-neoplastic agents in adults and children aged 4 months and older.

Administration

To be given by intravenous infusion or intramuscular injection.

For intravenous infusion, the reconstituted solution should be further diluted in 100 mL of normal saline and administered over 1 to 2 hours. For intramuscular injection the volume of reconstituted solution administered at a single injection site should not exceed 2 mL. Multiple injection sites should be used if this volume is exceeded.

Contraindications

Children under 4 months
Breastfeeding
History of pancreatitis
Pancreatitis
Pregnancy

Precautions and Warnings

Coagulopathy
Hepatic impairment
Renal impairment

Risk of pancreatitis in individuals with hypertriglyceridaemia
Advise ability to drive/operate machinery may be affected by side effects
Advise patient to avoid vincristine concurrently or immediately before dose
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Record name and batch number of administered product
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Perform coagulation screen before commencing therapy
Monitor ammonia levels if hyperammonaemia suspected
Monitor coagulation values
Monitor for signs and symptoms of pancreatitis
Monitor hepatic function regularly
Monitor periodically for signs or symptoms of hyperglycaemia
Monitor renal function
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum lipase in patients at risk of pancreatitis
Monitor uric acid levels
Advise patient to report headaches, seizures, confusion, visual disturbance
Antibodies to ingredient may develop
Discontinue permanently if acute pancreatitis occurs
Risk of pancreatitis
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue if severe hepatic changes occur
Discontinue in patients developing prolongation of coagulation markers
Female: Oral contraception may not be adequate during treatment
Male & female: Contraception required during & for 3 months after treatment
Advise patient to seek medical advice if delayed adverse event(s) occurs

Patients who develop hypersensitivity reactions to L-asparaginase from Escherichia coli may be able to continue treatment with crisantaspase as the enzymes are immunologically distinct.
Careful observation is required on re-exposure to L-asparaginase after any time interval which may increase the risk of anaphylactic reactions occurring.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

Pregnancy and Lactation

Pregnancy

Crisantaspase is contraindicated during pregnancy.

The manufacturer recommends that crisantaspase should not be used during pregnancy unless the potential benefit justifies the potential risk to the foetus.

There are no adequate data from the use of crisantaspase in pregnant women.

Based on effects on embryonal/foetal development shown in pre-clinical studies, crisantaspase should not be used during pregnancy unless clearly necessary.

The effect of concurrent therapies must also be considered.

Lactation

Crisantaspase is contraindicated during breastfeeding.

The manufacturer recommends that crisantaspase should be discontinued during breastfeeding.

It is not known if crisantaspase is excreted in human breast milk. The excretion of crisantaspase has not been studied in animals, however, because potential serious adverse reactions may occur in nursing infants, breastfeeding is contraindicated.

The effect of concurrent therapies must also be considered.

Side Effects

Abdominal pain
Allergic reaction
Anaemia
Anaphylactic shock
Anaphylaxis
Angioedema
Arthritis
Bleeding
Bronchospasm
Chills
Cholestatic jaundice
CNS depression
Coagulation disorders
Coma
Confusion
Convulsions
Diabetic ketoacidosis
Diarrhoea
Dizziness
Dysphagia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Encephalopathy
Erythema
Febrile neutropenia
Fever
Flushing
Haemorrhage
Headache
Hepatic failure
Hepatic impairment
Hepatic steatosis
Hepatomegaly
Hyperammonaemia
Hyperglycaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypoalbuminaemia
Hypotension
Hypoxia
Increase in alkaline phosphatase
Increase in blood urea nitrogen
Increase in bromsulphalein retention
Increase in plasma cholesterol
Increase in serum ALT/AST
Infections
Injection site reactions
Lethargy
Leukopenia
Liver toxicity
Mucositis
Musculoskeletal pain
Myalgia
Myocardial infarction
Nausea
Necrotising pancreatitis
Neurotoxicity
Neutropenia
Pain
Painful extremities
Pancreatitis
Paresis
Parotitis
Posterior reversible encephalopathy syndrome (PRES)
Pruritus
Pseudocysts
Pyrexia
Rash
Renal impairment
Respiratory distress
Rhinitis
Sepsis
Serum bilirubin increased
Serum creatinine increased
Somnolence
Thrombocytopenia
Thromboembolism
Thrombosis
Toxic epidermal necrolysis
Urticaria
Vomiting
Weight loss

Presentation

Powder for solution for injection containing crisantaspase (asparaginase from Erwinia chrysanthemi; Erwinia L-asparaginase)

Drugs List

Therapeutic Indications

Uses

Leukaemia - acute lymphoblastic

Treatment of acute lymphoblastic leukaemia in combination with other anti-neoplastic agents in adults and children aged 4 months and older.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.

Adults

Children

Administration

To be given by intravenous infusion or intramuscular injection.

For intravenous infusion, the reconstituted solution should be further diluted in 100 mL of normal saline and administered over 1 to 2 hours. For intramuscular injection the volume of reconstituted solution administered at a single injection site should not exceed 2 mL. Multiple injection sites should be used if this volume is exceeded.

Contraindications

Children under 4 months
Breastfeeding
History of pancreatitis
Pancreatitis
Pregnancy

Precautions and Warnings

Coagulopathy
Hepatic impairment
Renal impairment

Risk of pancreatitis in individuals with hypertriglyceridaemia
Advise ability to drive/operate machinery may be affected by side effects
Advise patient to avoid vincristine concurrently or immediately before dose
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Record name and batch number of administered product
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Perform coagulation screen before commencing therapy
Monitor ammonia levels if hyperammonaemia suspected
Monitor coagulation values
Monitor for signs and symptoms of pancreatitis
Monitor hepatic function regularly
Monitor periodically for signs or symptoms of hyperglycaemia
Monitor renal function
Monitor serum amylase in patients at risk of pancreatitis
Monitor serum lipase in patients at risk of pancreatitis
Monitor uric acid levels
Advise patient to report headaches, seizures, confusion, visual disturbance
Antibodies to ingredient may develop
Discontinue permanently if acute pancreatitis occurs
Risk of pancreatitis
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue if severe hepatic changes occur
Discontinue in patients developing prolongation of coagulation markers
Female: Oral contraception may not be adequate during treatment
Male & female: Contraception required during & for 3 months after treatment
Advise patient to seek medical advice if delayed adverse event(s) occurs

Patients who develop hypersensitivity reactions to L-asparaginase from Escherichia coli may be able to continue treatment with crisantaspase as the enzymes are immunologically distinct.
Careful observation is required on re-exposure to L-asparaginase after any time interval which may increase the risk of anaphylactic reactions occurring.

Posterior Reversible Encephalopathy Syndrome (PRES) also known as Reversible Posterior Leucoencephalopathy Syndrome (RPLS)
Posterior reversible encephalopathy syndrome (PRES) has been reported in some patients treated with this agent. If patients present with symptoms indicating PRES such as headache, altered mental state, seizures and visual disturbances, an MRI should be performed. If PRES is diagnosed, treatment should be discontinued and adequate blood pressure and seizure control administration is advisable. The safety of reinstating treatment in patients previously experiencing PRES is unknown.

Pregnancy and Lactation

Pregnancy

Crisantaspase is contraindicated during pregnancy.

The manufacturer recommends that crisantaspase should not be used during pregnancy unless the potential benefit justifies the potential risk to the foetus.

There are no adequate data from the use of crisantaspase in pregnant women.

Based on effects on embryonal/foetal development shown in pre-clinical studies, crisantaspase should not be used during pregnancy unless clearly necessary.

The effect of concurrent therapies must also be considered.

Lactation

Crisantaspase is contraindicated during breastfeeding.

The manufacturer recommends that crisantaspase should be discontinued during breastfeeding.

It is not known if crisantaspase is excreted in human breast milk. The excretion of crisantaspase has not been studied in animals, however, because potential serious adverse reactions may occur in nursing infants, breastfeeding is contraindicated.

The effect of concurrent therapies must also be considered.

Side Effects

Abdominal pain
Allergic reaction
Anaemia
Anaphylactic shock
Anaphylaxis
Angioedema
Arthritis
Bleeding
Bronchospasm
Chills
Cholestatic jaundice
CNS depression
Coagulation disorders
Coma
Confusion
Convulsions
Diabetic ketoacidosis
Diarrhoea
Dizziness
Dysphagia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Encephalopathy
Erythema
Febrile neutropenia
Fever
Flushing
Haemorrhage
Headache
Hepatic failure
Hepatic impairment
Hepatic steatosis
Hepatomegaly
Hyperammonaemia
Hyperglycaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Hypertriglyceridaemia
Hypoalbuminaemia
Hypotension
Hypoxia
Increase in alkaline phosphatase
Increase in blood urea nitrogen
Increase in bromsulphalein retention
Increase in plasma cholesterol
Increase in serum ALT/AST
Infections
Injection site reactions
Lethargy
Leukopenia
Liver toxicity
Mucositis
Musculoskeletal pain
Myalgia
Myocardial infarction
Nausea
Necrotising pancreatitis
Neurotoxicity
Neutropenia
Pain
Painful extremities
Pancreatitis
Paresis
Parotitis
Posterior reversible encephalopathy syndrome (PRES)
Pruritus
Pseudocysts
Pyrexia
Rash
Renal impairment
Respiratory distress
Rhinitis
Sepsis
Serum bilirubin increased
Serum creatinine increased
Somnolence
Thrombocytopenia
Thromboembolism
Thrombosis
Toxic epidermal necrolysis
Urticaria
Vomiting
Weight loss

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 ).

Further Information

Last Full Review Date: September 2020

Reference Sources

Summary of Product Characteristics: Erwinase, 10,000 unit/vial, lyophilisate for solution for injection. Jazz Pharmaceuticals UK. Revised April 2020.