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11/03/2014
Medication Safety with
Intrathecal Chemotherapy
Peter Gilbar
Toowoomba Hospital
Toowoomba, Australia
Learning Objectives
• To understand the role of intrathecal (IT)
chemotherapy
• To recognize the types of medication errors
that can potentially occur with IT
chemotherapy
• To understand what strategies for preventing
IT antineoplastic medication errors are
available and how to adopt them into current
practice
Background
• CNS malignant disease
– Present at initial diagnosis
• Demonstrated or suspected
– Site of relapse
• CNS - “Sanctuary site”
– Protected from effects of systemic antineoplastic
chemotherapy
• Blood-brain barrier
• Treatment strategies
– High-dose IV chemotherapy
– Intrathecal chemotherapy
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Intrathecal (IT) chemotherapy
• Goal
– Maximize CNS drug exposure in the CSF
– Reduce potential for systemic drug toxicity
• Medications used
– Methotrexate
– Cytarabine (cytosine arabinoside)
– Corticosteroids
• Increase cytotoxicity
• Reduce chemical arachnoiditis
• cytarabine
Potential for medication errors
• IT chemotherapy
– Given in conjunction with standard CT protocols
– Potential for medication errors
• Antineoplastic agents
– Narrow therapeutic index
– High potential for CNS toxicity
• Types of errors
– IT overdose
– Accidental IT administration
IT Overdose
• Methotrexate
– 22 reported cases in literature since 1967
– Reasons for error
• Concentrated solution used instead of standard strength
• IV high dose (syringe) given intrathecally
– Management
• CSF removal & exchange; IT carboxypeptidase G2
– Consequences
• 2 deaths
– >50 times dose; IT folinic acid as antidote
• Most cases caused no residual neurotoxicity
• Cytarabine
– 4 reported cases
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Inadvertent IT Administration
• Numerous reports
– Drugs intended for parenteral routes given IT
– Many more cases not reported or not recognised
• Consequences
– Profound neurotoxicity
• Commonly death (vinca alkaloids)
• Preventative strategies introduced
– Deaths still continue to occur
Vincristine (1)
• First reported in 1968
• 32 cases in published medical literature
– 25 deaths
• Length of survival 3 to 83 days
– Survivors – neurological sequale
• Latest deaths 2011 (USA, Thailand)
• 120 cases worldwide
– medication safety databases, legal claims,
regulatory agencies, drug companies or published
via local media sources
Vincristine (2)
• Fatalities
– Even when error recognised immediately
• Only fraction of dose given
– Progressive ascending myeloencephalopathy
• Management
– Prompt recognition
• Error discovered within 30 mns in all survivors
– Immediate instigation of CSF drainage and IT
exchange
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Vincristine (3)
• Reasons for error
– Multiple causes often identified
• Mistaking vincristine for IT medication
• even if different colours
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Mislabelled syringes
IV & IT drugs in treatment area at same time
Inexperienced medical staff
Treatment not in specialty unit
Treated outside normal working hours
Administration not double-checked
Incomplete warning label
Vindesine
• 1 case
• Error recognised immediately
– CSF washout & exchange
• Death
Asparaginase
• 1 case
• Error not recognized immediately
• Physician didn’t check label
– Thought syringe contained cytarabine
• No adverse effects
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Bortezomib
• 3 cases
• Given IT instead of IV
– Limited information
• Only reported on Eurovigilance database
• All fatal
Daunorubicin
• 1 case
• Early recognition
– CSF exchange (1 hour later)
• Death
Doxorubicin
• 2 cases
• CSF washout & exchange
• Severe acute encephalopathy
– resolved
• Complete paraplegia
– Some gradual neurological recovery
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Dactinomycin
• 1 case
• CSF washout & exchange
• Paraplegia
Reasons for errors
• Lapses in defensive barriers
– Active failures
• Unsafe acts by people in direct contact with patient or
system
– Drug given by wrong route, inadequate labelling, IV
medications in IT administration area, IT medications being
given before all other drugs are given
– Latent conditions
• Inherent problems within the system
– Inexperienced staff, medication in inappropriate form for
administration, unsuitable time or environment for
administration, lack of double checking
Prevention
• Every error involving the accidental IT administration of an
antineoplastic agent has occurred when that drug was prepared in a
syringe
• Deaths have occurred from larger volume syringes
• Abolish the syringe as a method of administration
for potentially neurotoxic medications
• Use minibags
– Suitable for most drugs
• Bortezomib
– Can be given SC
– Stability data
– Not available
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Mini-bags
• Premise
– Can’t connect a mini-bag to a spinal needle
– Prompt that something is wrong if attempted
• Adults
– In 50 mL sodium chloride 0.9%
– Give over 5 to 10 minutes
• Younger Children
– Lesser volume
– Slower infusion rate
Extravasation
• Risk NOT increased over syringes
• Gilbar & Carrington (JOPP 2006)
– Retrospective survey of 68 Australian hospitals
– Frequency of vincristine extravasations
• Syringes 0.03%
• Mini-bags 0.041%
• Administration techniques
– Identification of risk factors (patient, procedure)
– Education of patients
– Experience, trained & accredited nursing staff
Recommendations
• Only specifically trained and certified
healthcare professionals should prescribe,
dispense, prepare, administer and transport
antineoplastic medications
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Recommendations
• Vincristine and other vinca alkaloids should
NOT be prepared or administered in syringes
• Vincristine and other vinca alkaloids should be
prepared for administration ONLY in a smallvolume intravenous bag
– This is also advisable for other neutrotoxic
antineoplastic medications, such as anthracyclines
– Exception
• Bortezomib
– Can be given SC ; No stability data for infusions
Recommendations
• When intended for intravenous use,
methotrexate should NOT be prepared in a
syringe
• This should be prepared for administration in
an intravenous bag for infusion
• Concentrated solutions of methotrexate
should NOT be used when preparing
intrathecal doses
Recommendations
• Vincristine and other vinca alkaloids should be
clearly labelled with “For Intravenous Use
Only – Fatal if Given by Other Routes” both
on the intravenous bag and outer container
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Recommendations
• If possible, different delivery devices and
connectors should be used for medications to
be administered via the spinal route and those
used for other parenteral route
Recommendations
• All intrathecal drugs should be packaged
separately and clearly labelled with “For
Intrathecal Use Only” both on the syringe and
outer container
• Intrathecal drugs should be delivered to the
administration area separately from drugs to be
given by other routes
• Intrathecal drugs should be given only after drugs
prescribed by other routes have been
administered
Recommendations
• Intrathecal chemotherapy should be
administered only in an area where no other
antineoplastic drugs are accessible
– Ideally, patients receiving antineoplastic
medications by multiple routes should receive
them in different practice areas or these
medications should be given on different days
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References
• Gilbar PJ. Intrathecal chemotherapy: potential for medication error.
Cancer Nurs 2014; DOI:10.1097/NCC.0000000000000108
• Gilbar PJ, Dooley MJ. Review of case reports of inadvertent
intrathecal administration of vincristine: recommendations to
reduce occurrence. Asia Pac J Clin Oncol 2007;3:59-65
• Gilbar PJ, Carrington CV. The incidence of extravasation of vinca
alkaloids supplied in syringes or mini-bags. J Oncol Pharm Pract
2006;12:113-118
• Gilbar PJ, Dooley MJ, Brien J. Inadvertent administration of
vincristine: are we fulfilling our roles as oncology pharmacists? J
Oncol Pharm Pract 2004;10:187-189
• Gilbar P. Inadvertent intrathecal administration of vincristine: has
anything changed? J Oncol Pharm Pract 2011;18:155-157
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