CAUTIONS, FURTHER INFORMATION
▶Hypersensitivity reactionsSerious hypersensitivity reactions,
including life-threatening anaphylaxis, can occur—
asparaginase should only be administered when
appropriately trained staff and resuscitation facilities are
immediately available; in the event of a hypersensitivity
reaction, treatment should be stopped immediately and
appropriate management initiated. Manufacturer advises
an intracutaneous or small intravenous test dose can be
used but is of limited value for predicting which patients
will experience an allergic reaction.
lINTERACTIONS→Appendix 1 : asparaginase
lSIDE-EFFECTS
▶Common or very commonAbdominal pain.agitation.
anaemia.angioedema.appetite decreased.arthralgia.
back pain.bronchospasm.confusion.depression.
diarrhoea.disseminated intravascular coagulation.
dizziness.drowsiness.dyspnoea.embolism and
thrombosis.fatigue.flushing.haemorrhage.
hallucination.hyperglycaemia.hypersensitivity.
hypoalbuminaemia.hypoglycaemia.hypotension.
increased risk of infection.leucopenia.nausea.
neurological effects.oedema.pancreatitis.skin reactions
.thrombocytopenia.vomiting.weight decreased
▶UncommonHeadache.hyperammonaemia.
hyperuricaemia
▶Rare or very rareComa.consciousness impaired.diabetic
ketoacidosis.hepatic disorders.hyperparathyroidism.
hypoparathyroidism.ischaemic stroke.necrotising
pancreatitis.pancreatic pseudocyst.posterior reversible
encephalopathy syndrome (PRES).seizure.tremor
SIDE-EFFECTS, FURTHER INFORMATIONThere have been
rare reports of cholestasis, icterus, hepatic cell necrosis
and hepatic failure with fatal outcome; manufacturer
advises interrupt treatment if these symptoms develop.
lCONCEPTION AND CONTRACEPTIONManufacturer advises
effective contraception in men and women of child-
bearing potential during treatment and for at least
3 months after last dose; asparaginase may reduce
effectiveness of oral contraceptives—additional
precautions (e.g. barrier method) are required, see also
Pregnancy and reproductive functionin Cytotoxic drugs
p. 531.
lPREGNANCYManufacturer advises avoid unless
essential—toxicity inanimalstudies. See alsoPregnancy
and reproductive functionin Cytotoxic drugs p. 531.
lBREAST FEEDINGManufacturer advises avoid—no
information available.
lHEPATIC IMPAIRMENTManufacturer advises avoid in
severe impairment—no information available.
lMONITORING REQUIREMENTS
▶Manufacturer advises monitor trough serum asparaginase
levels 3 days after administration; consider switching to a
different asparaginase preparation if target levels not
reached—seek expert advice.
▶Manufacturer advises monitor bilirubin, hepatic
transaminases, and coagulation parameters before and
during treatment; in addition, monitor plasma and urinary
glucose, amylase, lipase, triglycerides, cholesterol and
serum protein levels during treatment.
lHANDLING AND STORAGEManufacturer advises store in a
refrigerator ( 2 – 8 °C)—consult product literature for storage
conditions after reconstitution and dilution.
lPATIENT AND CARER ADVICE
Driving and skilled tasksManufacturer advises
asparaginase has moderate influence on driving and
performance of skilled tasks—increased risk of dizziness
and somnolence.
lNATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) Decisions
SMC No. 1319/18
TheScottish Medicines Consortiumhas advised (April 2018 )
that asparaginase (Spectrila®) is accepted for use within
NHS Scotland when used as a component of antineoplastic
combination therapy for the treatment of acute
lymphoblastic leukaemia in paediatric patients from birth
to 18 years and adults.lMEDICINAL FORMS
There can be variation in the licensing of different medicines
containing the same drug.
Powder for solution for infusion
▶Spectrila(medac UK)A
Asparaginase 10000 unitSpectrila 10 , 000 unit powder for
concentrate for solution for infusion vials| 1 vialP£ 450. 00
(Hospital only)Crisantaspase 16-Mar-2017
lDRUG ACTIONCrisantaspase is the enzyme asparaginase
produced byErwinia chrysanthemi.lINDICATIONS AND DOSE
Acute lymphoblastic leukaemia|Acute myeloid leukaemia
|Non-Hodgkin’s lymphoma
▶BY INTRAVENOUS INJECTION, OR BY INTRAMUSCULAR
INJECTION, OR BY SUBCUTANEOUS INJECTION
▶Child:(consult local protocol)lUNLICENSED USEPreparations of asparaginase derived
fromEscherichia coliare available but they are not
licensed, they include:Medac®asparaginase andElspar®
asparaginase.
lCONTRA-INDICATIONSHistory of pancreatitis related to
asparaginase therapy
lCAUTIONSDiabetes (may raise blood glucose)
lINTERACTIONS→Appendix 1 : crisantaspase
lSIDE-EFFECTS
▶Common or very commonChills.coagulation disorders.
confusion.diarrhoea.dizziness.drowsiness.dyspnoea.
face oedema.fever.headache.hepatic disorders.
hypersensitivity.limb swelling.lip swelling.
neurotoxicity.pain.pallor.pancreatitis.seizures.skin
reactions.thrombosis
▶UncommonHyperglycaemia.hyperlipidaemia.hypoxia.
increased risk of infection.respiratory disorders
▶Rare or very rareArthritis reactive.coma.diabetic
ketoacidosis.dysphagia.dysphasia.encephalopathy.
haemorrhage.level of consciousness decreased.myalgia.
myocardial infarction.necrotising pancreatitis.
neutropenia.paresis.sepsis.thrombocytopenia
▶Frequency not knownAbdominal pain.flushing.
hyperammonaemia.hypertension.hypotension.nausea.
pseudocyst.vomiting
lALLERGY AND CROSS-SENSITIVITYChildren who are
hypersensitive to asparaginase derived from one organism
may tolerate asparaginase derived from another organism
but cross-sensitivity occurs in about 20 – 30 %of
individuals.
lCONCEPTION AND CONTRACEPTIONContraceptive advice
required, seePregnancy and reproductive functionin
Cytotoxic drugs p. 531.
lPREGNANCYAvoid. See also,Pregnancy and reproductive
functionin Cytotoxic drugs p. 531.
lBREAST FEEDINGDiscontinue breast-feeding.
lDIRECTIONS FOR ADMINISTRATIONFacilities for the
management of anaphylaxis should be available.BNFC 2018 – 2019 Cytotoxic responsive malignancy 551
Immune system and malignant disease8