Drugs List

Therapeutic Indications

Uses

Leukaemia - acute lymphoblastic

Combination treatment of acute lymphoblastic leukaemia (ALL).

Administration

For intramuscular injection or intravenous infusion.

When given as an intramuscular injection volume injected into one site should not exceed 2 ml in children and 3 ml in adults. Higher volumes should be split over several injection sites.

Intravenous infusion should be given over a period of 1 to 2 hours.

Contraindications

History of significant haemorrhage
Breastfeeding
Hepatic enzymes above 10 times the upper limit of normal
History of pancreatitis
History of thrombosis
Pancreatitis
Pregnancy
Serum bilirubin above 3 times upper limit of normal

Precautions and Warnings

Patients over 65 years
Coagulopathy
Hepatic impairment

Live virus vaccine should not be given for 3 months after treatment
Advise ability to drive/operate machinery may be affected by side effects
Advise patient to avoid vincristine for 12 hours 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
When intramuscular route used divide large doses among various sites
Monitor ammonia levels if hyperammonaemia suspected
Monitor bilirubin levels at baseline and prior to each dose
Monitor blood counts regularly
Monitor blood glucose
Monitor coagulation values
Monitor for signs of bone marrow depression
Monitor hepatic function
Monitor serum amylase and lipase regularly
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patients to report symptoms of acute pancreatitis immediately
Monitor for hypersensitivity reactions for 1 hour after administration
Neutralising antibodies may develop that decrease clinical efficacy
Potential for increased risk of bleeding
Risk of developing opportunistic infections
Use of live vaccines may cause severe reaction
Discontinue if pancreatitis is suspected
Discontinue if patient develops thrombus
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Do not restart treatment following confirmation of pancreatitis
Advise patients to avoid aspirin and NSAID use
Female: Non-hormonal contraception advised until 6 months after treatment
Female: Oral contraception may not be adequate during treatment
Male: Contraception required during and for 6 months after treatment

Asparaginase activity level should be monitored prior to each dose. Low asparaginase activity levels are often due to anti-asparaginase antibodies. In such cases a switch to a different asparaginase should be considered.

There is a possible risk of hepatotoxicity in patients with Philadelphia chromosome-positive ALL when treated in combination with imatinib, therefore use with caution in these patients.

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

Pegaspargase is contraindicated during pregnancy.

The manufacturer recommends that pegaspargase should not be used during pregnancy unless the clinical condition of the woman requires treatment with pegaspargase. No animal studies with pegaspargase have been performed at time of writing. However studies with L-asparaginase have shown teratogenicity in animals with doses within the therapeutic range.

The effect of concurrent therapies must also be considered.

Lactation

Pegaspargase is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding should be discontinued during pegaspargase treatment and should not be restarted until pegaspargase discontinuation. It is not known whether this agent or its metabolites are excreted in human breast milk, however there is potential for serious toxicity in the nursing infant.

The effect of concurrent therapies must also be considered.

Side Effects

Abdominal cramps
Abdominal pain
Acute renal failure
Alanine aminotransferase increased
Anaemia
Anaphylactic reaction
Ascites
Aspartate aminotransferase increased
Blood lipid changes
Blood urea increased
Cerebrovascular accident
Cholestasis
Coagulation disorders
Confusion
Convulsions
Decreased appetite
Decreased serum albumin
Development of neutralising antibodies
Diabetic ketoacidosis
Diarrhoea
Elevated amylase levels
Embolism
Febrile neutropenia
Fine tremor (usually hands)
Gamma glutamyl transferase (GGT) increased
Haemorrhage
Haemorrhagic pancreatitis
Headache
Hepatic disorders (fatty changes)
Hepatic failure
Hepatocellular necrosis
Hepatotoxicity
Hyperammonaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypofibrinogenaemia
Hypoglycaemia
Hypokalaemia
Hypoxia
Increase in plasma cholesterol
Increased partial thromboplastin time
Infections
Jaundice
Myelosuppression
Nausea
Necrotising pancreatitis
Neutropenia
Painful extremities
Pancreatitis
Parotitis
Peripheral motor neuropathy
Prothrombin time increased
Pseudocysts
Pyrexia
Rash
Reduced platelet count
Reduction of fibrinogen
Reversible posterior leucoencephalopathy syndrome (RPLS)
Seizures
Sepsis
Serum bilirubin increased
Somnolence
Stomatitis
Stroke
Superior sagittal sinus thrombosis
Syncope
Thrombosis
Toxic epidermal necrolysis
Unconsciousness
Urticaria
Vomiting
Weight loss

Presentation

Parenteral formulations of pegaspargase

Drugs List

Therapeutic Indications

Uses

Leukaemia - acute lymphoblastic

Combination treatment of acute lymphoblastic leukaemia (ALL).

Dosage

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

Adults

Children

Administration

For intramuscular injection or intravenous infusion.

When given as an intramuscular injection volume injected into one site should not exceed 2 ml in children and 3 ml in adults. Higher volumes should be split over several injection sites.

Intravenous infusion should be given over a period of 1 to 2 hours.

Contraindications

History of significant haemorrhage
Breastfeeding
Hepatic enzymes above 10 times the upper limit of normal
History of pancreatitis
History of thrombosis
Pancreatitis
Pregnancy
Serum bilirubin above 3 times upper limit of normal

Precautions and Warnings

Patients over 65 years
Coagulopathy
Hepatic impairment

Live virus vaccine should not be given for 3 months after treatment
Advise ability to drive/operate machinery may be affected by side effects
Advise patient to avoid vincristine for 12 hours 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
When intramuscular route used divide large doses among various sites
Monitor ammonia levels if hyperammonaemia suspected
Monitor bilirubin levels at baseline and prior to each dose
Monitor blood counts regularly
Monitor blood glucose
Monitor coagulation values
Monitor for signs of bone marrow depression
Monitor hepatic function
Monitor serum amylase and lipase regularly
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patients to report symptoms of acute pancreatitis immediately
Monitor for hypersensitivity reactions for 1 hour after administration
Neutralising antibodies may develop that decrease clinical efficacy
Potential for increased risk of bleeding
Risk of developing opportunistic infections
Use of live vaccines may cause severe reaction
Discontinue if pancreatitis is suspected
Discontinue if patient develops thrombus
Discontinue if posterior reversible encephalopathy syndrome (PRES) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Do not restart treatment following confirmation of pancreatitis
Advise patients to avoid aspirin and NSAID use
Female: Non-hormonal contraception advised until 6 months after treatment
Female: Oral contraception may not be adequate during treatment
Male: Contraception required during and for 6 months after treatment

Asparaginase activity level should be monitored prior to each dose. Low asparaginase activity levels are often due to anti-asparaginase antibodies. In such cases a switch to a different asparaginase should be considered.

There is a possible risk of hepatotoxicity in patients with Philadelphia chromosome-positive ALL when treated in combination with imatinib, therefore use with caution in these patients.

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

Pegaspargase is contraindicated during pregnancy.

The manufacturer recommends that pegaspargase should not be used during pregnancy unless the clinical condition of the woman requires treatment with pegaspargase. No animal studies with pegaspargase have been performed at time of writing. However studies with L-asparaginase have shown teratogenicity in animals with doses within the therapeutic range.

The effect of concurrent therapies must also be considered.

Lactation

Pegaspargase is contraindicated during breastfeeding.

The manufacturer recommends that breastfeeding should be discontinued during pegaspargase treatment and should not be restarted until pegaspargase discontinuation. It is not known whether this agent or its metabolites are excreted in human breast milk, however there is potential for serious toxicity in the nursing infant.

The effect of concurrent therapies must also be considered.

Side Effects

Abdominal cramps
Abdominal pain
Acute renal failure
Alanine aminotransferase increased
Anaemia
Anaphylactic reaction
Ascites
Aspartate aminotransferase increased
Blood lipid changes
Blood urea increased
Cerebrovascular accident
Cholestasis
Coagulation disorders
Confusion
Convulsions
Decreased appetite
Decreased serum albumin
Development of neutralising antibodies
Diabetic ketoacidosis
Diarrhoea
Elevated amylase levels
Embolism
Febrile neutropenia
Fine tremor (usually hands)
Gamma glutamyl transferase (GGT) increased
Haemorrhage
Haemorrhagic pancreatitis
Headache
Hepatic disorders (fatty changes)
Hepatic failure
Hepatocellular necrosis
Hepatotoxicity
Hyperammonaemia
Hypercholesterolaemia
Hyperglycaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypofibrinogenaemia
Hypoglycaemia
Hypokalaemia
Hypoxia
Increase in plasma cholesterol
Increased partial thromboplastin time
Infections
Jaundice
Myelosuppression
Nausea
Necrotising pancreatitis
Neutropenia
Painful extremities
Pancreatitis
Parotitis
Peripheral motor neuropathy
Prothrombin time increased
Pseudocysts
Pyrexia
Rash
Reduced platelet count
Reduction of fibrinogen
Reversible posterior leucoencephalopathy syndrome (RPLS)
Seizures
Sepsis
Serum bilirubin increased
Somnolence
Stomatitis
Stroke
Superior sagittal sinus thrombosis
Syncope
Thrombosis
Toxic epidermal necrolysis
Unconsciousness
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: August 2019

Reference Sources

Summary of Product Characteristics. Oncaspar 750 U/ml solution for injection/infusion. Servier Laboratories Ltd. April 2019
Summary of Product Characteristics. Oncaspar 750 U/ml powder for solution for injection/infusion. Servier Laboratories Ltd. April 2019