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Preventing Vincristine Sulfate Medication Errors
Lisa Schulmeister, RN, MN, CS, OCN
Key Points . . .
Purpose/Objectives: To review the clinical pharmacology of vincris-
tine sulfate, describe three types of medication errors associated with its
use, and suggest strategies for vincristine sulfate medication error pre-
Vincristine is administered by IV only.
Data Sources: Published books and journal articles, online newslet-
The major toxicity associated with vincristine is neurotoxicity
ters and documents, pharmaceutical manufacturers' package inserts, and
that is dose related. Neurotoxicity usually is reversible with
personal experience.
discontinuation of the drug.
Data Synthesis: Medication errors involving vincristine sulfate include
Vincristine overdoses cause sensory impairment and motor
overdosage (wrong dose), name confusion (wrong drug), and incorrect
nerve involvement that can be debilitating and even fatal.
administration (wrong route).
Conclusions: Vincristine medication errors are preventable errors that
Inadvertent intrathecal vincristine administration is usually fa-
usually result in serious patient harm and often are lethal.
tal, and every effort to prevent this type of medication error
Implications for Nursing: Nurses need to be aware of the types of
should be employed.
medication errors that can occur with chemotherapy agents and be fa-
miliar with clinical signs and symptoms associated with these errors.
Nurses also need to promote patient safety by implementing specific
strategies to prevent vincristine medication errors.
Goal for CE Enrollees:
To enhance nurses' knowledge about the causes of and
ince its introduction in 1963, vincristine sulfate, or vin-
measures to prevent vincristine sulfate medication errors.
cristine as it is commonly known, has been used to treat
a variety of cancers, such as acute lymphocytic leuke-
Objectives for CE Enrollees:
mia, Hodgkin disease, non-Hodgkin lymphomas, rhabdomyo-
On completion of this CE, the participant will be able to
sarcoma, neuroblastoma, and Wilms tumor. Because it has
1. Review the clinical pharmacology of vincristine sulfate.
very limited efficacy as a single agent, this drug is given as a
2. Describe the types of medication errors that most com-
component of multidrug chemotherapy regimens (Rowinsky
monly occur during vincristine sulfate administration.
& Donehower, 2001; U.S. Food and Drug Administration
3. Discuss strategies that may decrease the risk of medication
[FDA], 2004).
error during vincristine sulfate administration.
Vincristine has been used widely for many years, and, as a
result, most oncology nurses are very familiar with it. How-
ever, despite its extensive long-term use, vincristine has been
associated repeatedly with various medication errors. This
sulting in the arrest of dividing cells at the metaphase stage and,
because of this action, sometimes is referred to as an antimic-
article reviews this agent and these errors, which include over-
dosage (wrong dose), name confusion (wrong drug), and in-
rotubule agent. Vincristine has a triphasic serum decay pattern;
correct administration (wrong route).
the initial, middle, and terminal half-lives are 5 minutes, 2.3
Clinical Pharmacology
Lisa Schulmeister, RN, MN, CS, OCN  , is an oncology nursing con-
sultant in River Ridge, LA. (Submitted March 2004. Accepted for
Vincristine sulfate is the salt of an alkaloid obtained from a
publication April 19, 2004.) (Mention of specific products and opin-
flowering herb, the Madagascar periwinkle plant (Catharanthus
ions related to those products do not indicate or imply endorsement
roseus, formerly classified as Vinca rosea Linn, which caused
by the Oncology Nursing Forum or the Oncology Nursing Society.)
it to be called a vinca alkaloid) (Greuter et al., 1999). Vincris-
tine inhibits microtubule formation in the mitotic spindle, re-
Digital Object Identifier: 10.1188/04.ONF.E90-E98
From 19702002, 18 case reports of patients who inadvert-
hours, and 85 hours, respectively. The primary route for ex-
ently received overdoses of vincristine were published. Vin-
cretion is the liver. Approximately 80% of a dose of vincris-
cristine overdoses resulted from decimal errors or errors in
tine appears in the feces, and 10% can be found in urine.
dose calculation or administration schedule. Signs and symp-
Within 1530 minutes following vincristine administration,
toms of vincristine overdose included sensory impairment and
about 90% of the bioavailable drug is distributed from the
motor nerve involvement beginning within hours of the over-
blood into the tissue, where it remains tightly bound (Facts
dose. Involvement of cranial nerves III, IV, V, VI, VII, and X
and Comparisons, 2004; Rowinsky & Donehower, 2001).
was reported, which caused loss of corneal reflexes, facial
Intended for IV use only, vincristine is supplied as a sterile,
weakness, jaw pain, and hoarseness. Most patients developed
preservative-free solution at a concentration of 1 mg/ml in 1
a paralytic ileus, and two experienced atony of the bladder.
mg and 2 mg vials that are refrigerated until use. The pH of
All patients experienced some degree of cerebral dysfunction,
vincristine ranges from 45; however, the drug should not be
including insomnia, agitation, confusion, and, occasionally,
diluted in solutions that raise or lower the pH outside the range
hallucinations and coma. Eleven patients had generalized sei-
of 3.55.5. Prepared solutions must be refrigerated and pro-
zure activity one to seven days following the overdose. Vin-
tected from light. Vincristine can be given by IV bolus into the
cristine overdosage also caused severe bone marrow depres-
tubing of an infusing IV fluid or added to 50 ml infusion bags
sion and inappropriate antidiuretic hormone (ADH) secretion.
of 0.9% saline or 5% dextrose in water and rapidly infused
Presumably, vincristine acts on the hypothalamic nuclei to
(Facts and Comparisons, 2004; Gensia Sicor Pharmaceuticals,
stimulate release of ADH. Fever also reportedly occurred.
Inc., 1999; Mayne Pharma [USA Inc.], 2004).
Although its exact mechanism is not known, fever may be re-
Extravasation of vincristine results in irritation and tissue
lated to direct hypothalamic stimulation. Patients who re-
necrosis (Facts and Comparisons, 2004). Therefore, vesicant
ceived large overdoses of vincristine did not survive. Causes
precautions are used when administering this drug. These pre-
of death included widespread hemorrhage and overwhelming
cautions include ensuring the presence of a blood return be-
infection. Two patients who received small overdoses recov-
fore, during, and after vincristine administration; continuously
ered, but they had symptoms that were slower in onset and
monitoring patients for signs and symptoms of an extravasa-
milder than those observed in patients who received 10-fold
tion while vincristine is being administered; avoiding the use
overdoses of vincristine (Berenson, 1971; Casteels-Vann
of infusion pumps for vesicant administration; and educating
Daele, Beirinckx, & Baines, 1977; Chae, Moon, & Kim, 1998;
patients about extravasation prevention and detection (Brown
Grush & Morgan, 1979; Jochimsen, 1982; Kaufman et al.,
et al., 2001).
1976; Kosmidis et al., 1991; Maeda et al., 1987; Stones, 1998;
The major toxicity associated with vincristine is neurotox-
Thomas, Braat, Somers, & Goudsmit, 1982; Wakem &
icity, which may be dose limiting. Typically occurring as a
Bennett, 1975).
symmetric peripheral neuropathy that is dose related, this tox-
Not all vincristine overdoses are published in the literature;
icity usually can be reversed by discontinuing the drug. A
therefore, the extent of this type of medication error is un-
common presenting symptom is paresthesia of the hands or
known. The author is aware of two unpublished incidents of
feet. Further neurologic toxicity, including loss of deep tendon
lethal vincristine overdoses that occurred in 2000 and 2002
reflexes, severe pain, muscle weakness, foot or wrist drop, and
that prompted legal action.
rarely paralysis, can develop. Vincristine-induced autonomic
Vincristine has no antidote. Three of the patients in the
dysfunction also may occur; symptoms include abdominal
published case reports were treated with leucovorin (two pa-
pain and constipation and, in severe cases, paralytic ileus
tients received 15 mg eight times daily for three days starting
(Gensia Sicor Pharmaceuticals, Inc., 1999).
48 hours after the vincristine overdose, and one patient re-
The usual dose of vincristine for children weighing 10 kg or
more is 2 mg/m2 once a week. The adult dose is 1.4 mg/m2,
ceived 12 mg four times daily for five days starting 24 hours
after the vincristine overdose), based on the observation of a
usually not to exceed 2 mg per dose. Dose reduction (usually
protective effect of leucovorin in mice that were given a lethal
50%) may be required for patients with hepatic impairment
dose of vincristine. Despite leucovorin administration, one
(e.g., serum bilirubin > 3 mg/dl) (Gensia Sicor Pharmaceuti-
patient died from bone marrow aplasia and hemorrhage 68
cals, Inc., 1999; Mayne Pharma [USA Inc.], 2004).
hours following a 10-fold vincristine overdose. The two pa-
tients who also received leucovorin following a 10-fold vin-
cristine overdose recovered, although a more rapid recovery
Accidental overdoses of vincristine often have been attrib-
time was not observed when they were compared retrospec-
uted to omitted or unclear decimal points in the dose pre-
tively to patients who survived a vincristine overdose but did
scribed. This type of medication error results in a 10-fold
not receive leucovorin (Grush & Morgan, 1979; Thomas et al.,
overdose of the drug. For instance, in an early case report of
a vincristine overdose, a decimal point was omitted from a
Because vincristine is metabolized rapidly by the liver and
handwritten order for a 3.2 mg dose of vincristine; as a result,
its metabolites are excreted primarily via the biliary system to
a dose of 32 mg was administered. The overdose was discov-
the feces, only very small amounts of the drug appear in dialy-
ered on the day following treatment when the 12-year-old
sate. Therefore, hemodialysis is not considered to be helpful
patient experienced pain in her legs and bled from previous
following a vincristine overdose (Gensia Sicor Pharmaceuti-
venipuncture sites. Marked abdominal distention developed,
cals, Inc., 1999).
followed by confusion, stupor, seizures, and a coma. Support-
Treatment of a vincristine overdose is symptomatic and
ive measures were ineffective, and the patient died 33 hours
supportive. Close patient monitoring is necessary, and seizure
after the overdose of vincristine was administered (Kaufman,
precautions should be implemented. Because myelosup-
Kung, Koenig, & Giammona, 1976).
pression typically occurs, daily complete blood cell counts are
indicated, and blood product support may be required. Serum
electrolytes and fluid balance are monitored closely to
promptly detect inappropriate ADH secretion. The patient's
abdomen is observed for distention and auscultated for bowel
sounds, and abdominal x-rays are indicated when an ileus is
Vincristine overdoses are preventable medication errors.
Healthcare providers need to be familiar with chemotherapeu-
tic agents and their usual dose range and administration sched-
ule. Any dose containing a decimal point needs to be written
Note. Italics are used in the word "vincristine" to help distinguish it from vin-
clearly or, preferably, typed or electronically entered. Trailing
zeros, as in 2.0 mg, need be avoided; 2 mg should be used
Figure 1. Example of "Tall Man" Lettering on Vinblastine
instead to avoid confusion and potential overdose. Each page
Sulfate Label to Help Distinguish the Drug From Similarly
of order forms that contain multiple layers needs to be in-
Spelled Vincristine Sulfate
spected to ensure that orders are clear and complete (e.g., a
decimal point may not be visible because the person writing
the orders did not press down hard enough while writing).
tween a syringe containing vincristine and a syringe of L-as-
Orders that are unclear about the administration schedule or
paraginase that each of the patients was scheduled to receive
do not specify the length of treatment need to be clarified;
on the same day. The three children who received injections
vincristine overdoses also have occurred when the drug was
in the thigh were treated topically with cold compresses and
administered daily instead of weekly as prescribed (Joch-
an injection of 8.4% sodium bicarbonate to the affected areas.
imsen, 1982).
One of these children experienced pain after the inadvertent
injection of vincristine, but none experienced any delayed ad-
Name Confusion
verse sequelae. For the fourth child who received the gluteal
The vinca alkaloids represent a group of drugs that have been
injection of vincristine, hot compresses were applied for 16
called "look-alike, sound-alike" drugs (Hoffman & Prouix,
hours, beginning about six hours after the injection. Slight
2003). The vinca alkaloids include agents with similar sound-
pain and erythema developed at the injection site but resolved
ing names: vincristine, vinblastine, vindesine, and vinorelbine.
completely within two weeks (Clark, Gallegos, & Bleyer,
When these drug names are handwritten on order sheets, espe-
1997; Olcay & Safak, 2003).
cially in script, the drugs being prescribed may be unclear.
Because it is a vesicant, vincristine has the potential to
Confusion over similar names and inadvertent selection of the
cause tissue necrosis if inadvertently given subcutaneously or
wrong product when drugs with similar names are stocked
intramuscularly. Nurses giving chemotherapy should care-
closely together has been reported to cause "wrong drug" che-
fully read chemotherapy orders and drug labels, especially
motherapy medication errors (Boyle, Schulmeister, Lajeunesse,
when multiple syringes are prepared for one patient, and ad-
& Anderson, 2002; Schulmeister, 1999).
minister the drugs per the correct route of administration.
Strategies to prevent wrong drug errors for look-alike,
Heat application is recommended for vincristine extrava-
sound-alike drugs have been developed by pharmaceutical
sations (Brown et al., 2001). In contrast, cold was applied
manufacturers and healthcare providers. For instance, manu-
(along with infiltration of the areas with sodium bicarbonate) to
facturers highlight or emphasize a certain part of a drug's
the injection areas of the three children who had been injected
name on its label. Mayne Pharma (USA Inc.) in Paramus, NJ,
inadvertently with vincristine in their thighs (Clark et al., 1997).
uses what is termed "tall man" lettering when labeling its vi-
The authors of these case reports noted that tissue breakdown
als (e.g., vinCRISTINE Sulfate Injection), whereas Gensia
did not occur. Although sodium bicarbonate was used as a vin-
Sicor Pharmaceuticals, Inc., in Irvine, CA, uses italics (e.g.,
cristine antidote, its role in managing vincristine extravasations
Vincristine Sulfate Injection) to more clearly distinguish vin-
or injections into the tissue has not been established. Hyal-
cristine from vinblastine (see Figure 1). To reduce potential
uronidase administered subcutaneously in a circumferential
confusion among the vinca alkaloids, healthcare providers
manner around the needle site has been used as an antidote for
who do not use automated dispensing systems should avoid
vinca alkaloid extravasations since the mid-1980s (Dorr &
stocking look-alike, sound-alike drugs in close proximity to
Alberts, 1985). Menzel and Farr (1998) postulated that hyal-
one another and label storage bins with high-alert warning
uronidase repairs tissue damage by promoting cell turnover, re-
stickers. Education also is paramount so that everyone who
modeling the tissue's extracellular matrix components, and
prescribes, transcribes, prepares, handles, and administers
stimulating angiogenesis (i.e., the formation of capillaries).
chemotherapy is well informed about vinca alkaloids and the
From 20012004, the injectable formulation of hyal-
potential for name confusion.
uronidase was available only through pharmacies that com-
pound the drug. Wyeth-Lederle (now Wyeth-Ayerst in Phila-
Incorrect Route of Administration
delphia, PA) discontinued manufacturing the drug in 2001. On
May 5, 2004, the FDA approved Vitrase (hyaluronidase for
Inadvertent Intramuscular Injection
injection, Cardinal Health, Albuquerque, NM) as an adjuvant
treatment to increase the absorption and dispersion of other in-
Vincristine is given by IV only. In published anecdotal ac-
jected drugs. The product is provided in vials containing 6,200
counts, the drug has been injected inadvertently into the thighs
units of hyaluronidase that are being distributed as samples.
of three children and into the gluteal muscle of a fourth. This
FDA permission to market the product in vials containing 150
type of medication error occurred as a result of a mix-up be-
hospital apologizes again . . . and steps will be taken, again"
units of hyaluronidase in 1 ml of a ready-to-use solution is
(Berwick, 2001, p. 247). Berwick raises the interesting ques-
pending. After permission is obtained (estimated by Decem-
tion of how could this error happen--again and again?
ber 2004), commercial sale of the product will begin (Ameri-
can Society of Health-System Pharmacists [ASHSP], 2004a,
Inadvertent intrathecal vincristine administration usually
has occurred when a syringe containing vincristine intended
for IV administration was confused with another syringe con-
Hyaluronidase also can be obtained from pharmacies that
taining a drug to be given intrathecally (usually methotrexate
compound the drug. However, compounded drugs are not
or sometimes cytarabine). On other occasions, healthcare pro-
FDA-approved products because the FDA has no control
viders assumed vincristine was an additional intrathecal drug
over the quality or consistency of the manufacturing process.
to be injected when syringes were mislabeled (Fernandez,
In addition, compounding practices and the legal restrictions
Esau, Hamilton, Fitzsimmons, & Pritchard, 1998). Although
on these practices vary from state to state (ASHSP, 2004a).
intrathecal chemotherapy typically is administered by physi-
Clinicians need to screen suppliers that compound hyal-
cians and, in some cases, advanced practice nurses, this pro-
uronidase injection and inquire about their quality control
cedure often involves other nurses or healthcare personnel,
such as medical assistants. Nurses or medical assistants may
Recommendations for managing the inadvertent injection
be responsible for preparing patients to receive intrathecal
of vincristine cannot be made because few case reports have
chemotherapy, setting up the required equipment and sup-
been published and patients have been treated in different
plies, and assisting during the procedure. Presence during in-
ways. However, healthcare professionals should assess injec-
trathecal chemotherapy administration provides nurses with
tions sites as well as pain in patients who inadvertently receive
an opportunity to verify that the correct drug and dose are
vincristine intramuscularly rather than by IV. Applying heat
being administered.
with warm compresses and elevating and resting the affected
In published accounts, the typical course of events after
area also may be helpful.
inadvertent intrathecal vincristine administration was rapid
Inadvertent Intrathecal Administration
sensory and motor dysfunction followed by encephalopathy,
coma, and death. Early signs and symptoms included tremors,
Administration of vincristine via the spinal route (intra-
disorientation, and nausea and vomiting. Progressive deterio-
thecally via a lumbar puncture or intraventricularly via an
ration ensued, and patients became unresponsive within one
Ommaya reservoir) rather than by IV as prescribed causes se-
week. Ascending paralysis occurred in six patients. The time
vere neurologic damage and often is fatal. In addition to harm-
to death ranged from 783 days and averaged 10 days for the
ing patients, inadvertent intrathecal administration of vincris-
17 patients who died (al Fawaz, 1992; Bain, Lantos, Djurovic,
tine has prompted legal action, including malpractice and
& West, 1991; Dettmeyer, Driever, Becker, Wiestler, &
manslaughter charges. In a review of 17 lethal incidents that
Madea, 2001; Fernandez et al., 1998; Gaidys, Dickerman,
occurred in the United Kingdom from 19701999 that re-
Walters, & Young, 1983; ISMP, 1998, 2000, 2003; Kwack et
sulted in physicians being charged with manslaughter, two
al., 1999; Lau, 1996; Manelis, Freundich, Ezekiel, & Doron,
were incidents in which vincristine was given intrathecally
1982; Meggs & Hoffman, 1998; Shepherd, Steuber, Starling,
(Ferner, 2000).
& Fernbach, 1978; Slyter, Liwnicz, Herrick, & Mason, 1980;
The first reported account of inadvertent intrathecal vincris-
Williams et al., 1983).
tine administration was published in 1968 (Schochet, Lam-
The patients who lived the longest were a three-year-old
pert, & Earle, 1968). Since then, at least 20 deaths from inad-
(time to death 83 days) (Alcaraz, Rey, Concha, & Medina,
vertent intrathecal vincristine administration are known to
2002) and a 59-year-old woman with acute lymphocytic leu-
have occurred in the United States, Canada, the United King-
k e m i a who inadvertently received 2 mg of vincristine
dom, Germany, Saudi Arabia, Singapore, and Korea. In the
intrathecally (cytarabine was intended to be injected into her
United Kingdom alone, the National Health Service re-
Ommaya reservoir and vincristine was intended to be given by
corded 14 incidents of inadvertent intrathecal vincristine ad-
IV). She became deeply comatose on day 11 and died on day
ministration that occurred from 19862001 (Woods, 2001).
40 without regaining any neurologic function (Meggs &
Lethal inadvertent intrathecal vincristine administration is
Hoffman, 1998).
documented to have occurred as recently as 2003 in the
Upon autopsy, typical findings caused by inadvertent in-
United States (Institute for Safe Medication Practices [ISMP],
trathecal vincristine administration included grossly edema-
tous and congested brain and spinal cord tissue with axonal
The incidence of inadvertent intrathecal vincristine admin-
degeneration and myelin loss of the spinal nerves (Kwack et
istration is not known. Some of these incidents, particularly
al., 1999; Williams et al., 1983). Lau (1996) summarized this
lethal events, prompt publication. Sometimes these incidents
type of finding by describing it as "brain death."
are reported to organizations such as the ISMP but are not
One report of a patient surviving inadvertent intrathecal
published as case reports. Inadvertent intrathecal vincristine
vincristine administration involved a seven-year-old with
administration also occasionally has received media attention.
acute lymphocytic leukemia who, one year after diagnosis,
In a February 2001 editorial in the BMJ, Donald Berwick,
received maintenance chemotherapy that included IV vincris-
president and chief executive officer of the Institute for
tine and intrathecal methotrexate. She inadvertently received
Healthcare Improvement in Boston, described his frustration
her usual vincristine dose intrathecally, and the error was de-
in learning of repeated accounts of inadvertent intrathecal
tected halfway through the injection (the patient received ap-
vincristine administration by writing, "Again, a young patient
proximately 0.5 mg vincristine). Immediate neurosurgical
with leukemia is dying, not from his disease, but from an er-
intervention included an exchange of cerebrospinal fluid
roneous intrathecal injection of vincristine, intended for intra-
(CSF) with Ringer's lactate. The patient then was taken to the
venous use. Again, the newspapers express outrage . . . the
operating room in an upright position, and an intraventricular
Qualifications of staff who order, prepare, handle, and administer intrathe-
drain was inserted. After surgery, the patient was responsive
cal chemotherapy are delineated.
and was taken to the intensive care unit where her subarach-
Specialized training in intrathecal chemotherapy administration is required.
noid space was flushed continuously with Ringer's lactate for
A separate order form specifically for intrathecal chemotherapy is used.
24 hours. She also received 10 g of glutaminic acid IV fol-
lowed by oral doses of 500 mg three times daily. Five days
postoperatively, the patient experienced lower extremity pain
For children 10 years of age and older, vincristine is diluted to a concentra-
and weakness that progressed to complete paraplegia. She
tion of 0.1 mg/ml and doses are provided in a 10 ml or larger syringe.
For children younger than the age of 10, vincristine is provided undiluted at
also developed a neurogenic bladder that required intermittent
a concentration of 1 mg/ml in a syringe that is size appropriate for measure-
catheterization. Seven years later, she remained in remission
ment of the dose.
but did not regain motor function of her legs and continued to
Intrathecal drugs are issued and received by designated staff.
have a neurogenic bladder (Iqbal, Abdullah, Tuner, & Al-
Intrathecal drugs are packed and transported separately from IV or other
Sudairy, 2002). The researchers could not determine whether
this patient's survival occurred as a result of undergoing im-
"Do not disturb" signs are posted while intrathecal chemotherapy is admin-
mediate CSF fluid exchange or if she survived because, unlike
other patients who received a full dose of IV vincristine in-
Compliance checklists are completed routinely.
trathecally, she received about half of the vincristine dose.
Figure 2. Key Components of the United Kingdom's
Another patient who inadvertently received a partial dose of
Department of Health Guidelines for Safe Administration of
vincristine intrathecally survived but experienced continued
Intrathecal Chemotherapy
neurotoxicity, including a neurogenic bladder, 24 months fol-
lowing the incident (Zaragoza, Ritchey, & Walter, 1995). The
Note. Based on information from Department of Health, 2003.
only published account of survival following a full dose of
vincristine inadvertently administered intrathecally was a 23-
this USP standard, another fatality occurred after vincristine
year-old patient with lymphoblastic lymphoma who under-
was dispensed without this warning label on the syringe and
went immediate CSF drainage; however, he developed as-
outer wrapper; the drug inadvertently was administered
cending paralysis and became comatose after two days. The
intrathecally along with the prescribed intrathecal chemo-
patient remained comatose for 10 months at which point his
therapy (ISMP, 2003).
disease recurred but was not treated (Bleck & Jacobsen,
In Australia, most hospitals prepare vincristine in a small-
volume infusion bag of 50 ml normal saline as opposed to a
The three-year-old who inadvertently received intrathecal
syringe. Then, the drug is administered to adults over 510
vincristine and died 83 days later also received CSF drainage
minutes. The same approach is used for pediatric patients, but
and CSF fluid exchange. Her unusually prolonged time to
with a smaller volume and slower rate of infusion (Stefanou
death following inadvertent intrathecal vincristine administra-
& Dooley, 2003). According to Stefanou and Dooley, "This
tion was attributed to the immediate detection of the error and
is the only method of completely eradicating the risk of this
prompt CSF drainage and lavage (Alcaraz et al., 2002).
drug accidentally being given intrathecally . . . since all pub-
The rationale for immediate CSF drainage and lavage is to
lished reports of intrathecal vincristine administration have
dilute and remove the inadvertently administered vincristine,
been associated with preparation of the drug in a syringe" (p.
thus limiting neurologic damage. This is the only known an-
ecdotally documented treatment (Al Ferayan, Russell, Al
Womer and Bickert (2003) reported that routinely diluting
Wohaibi, Awada, & Scherman, 1999). Its success appears to
vincristine and administering it as a short infusion have been
be contingent on immediate detection of the error and likely
debated in national pharmacy meetings and Internet mailing
is influenced by the amount of vincristine inadvertently ad-
lists. The researchers did not advocate this approach, noting
ministered intrathecally.
that, in pediatric patients, administering vincristine through a
Because the consequences of inadvertent intrathecal vinc-
peripheral IV and a vincristine infusion, rather than bolus ad-
ristine administration are catastrophic, every effort to prevent
ministration, greatly increases the risk of extravasation injury.
this type of medication error should be used. In the United
In developing an institutional policy for intrathecal che-
Kingdom, the Department of Health has taken a leading role
motherapy administration, several concepts warrant inclu-
in preventing accidental intrathecal vincristine administration
sion. First, chemotherapy of any kind should be given only
by issuing mandates designed to promote the safe administra-
tion of all intrathecal chemotherapy (see Figure 2).
Not as much has been done in the United States to help pre-
vent inadvertent intrathecal vincristine administration. Data
from deaths resulting from inadvertent intrathecal vincristine
administration have led to changes in United States Pharma-
copeial Convention, Inc. (USP), requirements for manufac-
turers and pharmacies that package and prepare ready-to-use
doses of vincristine. Each dose of vincristine now has spe-
cific cautionary labeling. A label that states "FATAL IF
ONLY" is adhered to all syringes (see Figure 3). Each sy-
Figure 3. Example of Syringe Label That Is Affixed to
ringe then is placed in an overwrap that also contains this
Prepared Doses of Vincristine
warning (see Figure 4) (Williams, 2002). However, despite
cal drugs, for which such a large volume is not given, may help
to reduce the potential for inadvertent intrathecal vincristine ad-
A disturbing trend in the literature regarding inadvertent in-
trathecal vincristine administration is the use of "intrathecal
vincristine" without the word "inadvertent." Titles of journal
articles, such as "Intrathecal Vincristine: Fatal Myeloenceph-
alopathy Despite Cerebrospinal Fluid Perfusion" (Alcaraz et
al., 2002) or "Intrathecal Vincristine: Long-Term Survivor of
Potentially Fatal Chemotherapeutic Error" (Iqbal et al., 2002),
in some ways make it sound as if intrathecal vincristine is an
accepted treatment. To avoid confusion, clinicians and authors
should consistently refer to this type of medication error as
"inadvertent intrathecal vincristine administration," "acciden-
tal intrathecal vincristine administration," or "erroneous in-
trathecal vincristine administration."
Figure 4. Example of Vincristine Box Label, Syringe Label,
and Plastic Overwrap
"The system of medical care, like all other systems, is safe
only if human error is recognized as inevitable and the system
by appropriately trained staff. Intrathecal and IV chemo-
is designed to minimize the consequences" (Ferner, 2000, p.
therapy should never be dispensed or delivered together.
1215). In many instances, human error is responsible for, or
When a patient is scheduled to receive intrathecal and IV che-
contributes to, serious medication errors. Medication errors
motherapy treatment, the treatment should be viewed as two
involving the chemotherapeutic agent vincristine, which has
distinct procedures that are to be performed at different points
a very short half-life and is rapidly tissue bound, can be debili-
in time. At least two clinicians should independently verify
tating or even fatal. Its primary toxicity is neurologic, and
intrathecal medications prior to their administration. Intrath-
symptoms of neurotoxicity are amplified when overdoses of
ecal chemotherapy should be given in designated locations
vincristine are administered inadvertently. In addition, vinc-
only, and, ideally, the pharmacy staff should deliver intrath-
ristine is not a myelosuppressive agent, but when overdoses
ecal chemotherapy immediately before use. Prepared intrath-
are administered inadvertently, patients are at high risk for
ecal chemotherapy never should be stored or placed on a
bleeding and infection. Accidental injection of vincristine, a
counter on a patient care unit or in a patient's room (Dyer,
drug intended for IV use only, into the CSF or ventricle of the
2001; ISMP, 2003; Root & the British Oncology Pharmacy
brain results in profound neurologic sequelae and usually
Association, 2001). In addition, Laws (2001) suggested that
death. Lastly, confusion of vincristine with other vinca alka-
medical product manufacturers should develop syringes and
loids can result in the incorrect drug being administered.
equipment for epidural use that are noninterchangeable with
All of these vincristine medication errors are preventable.
IV products.
Increased awareness of the potential severity of these errors,
Creation of a specific IV vincristine administration policy
combined with designing systems and using practices to pre-
may be warranted in facilities where both IV vincristine and in-
vent medication errors, has the greatest potential for eradicat-
trathecal medications are administered. Adherence to the USP
ing vincristine medication errors.
vincristine labeling standard is essential. Methods to distinguish
vincristine from intrathecal medications also can be considered.
Author Contact: Lisa Schulmeister, RN, MN, CS, OCN, can be
Dispensing vincristine in small-volume infusion bags or dilut-
reached at lisaschulmeister@hotmail.com, with copy to editor at
ing the dose to at least 10 ml to help differentiate it from intrathe-
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system effects. Journal of Neurology, 238, 230234.
tine: Fatal myeloencephalopathy despite cerebrospinal fluid perfusion.
Berenson, M.P. (1971). Recovery after inadvertent massive overdosage of
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al Fawaz, I.M. (1992). Fatal myeloencephalopathy due to intrathecal vincris-
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tine administration. Annals of Tropical Paediatrics, 12, 339342.
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(1999). Cerebrospinal fluid lavage in the treatment of inadvertent intrathe-
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ONF Continuing Education Examination
Preventing Vincristine Sulfate Medication Errors
b. The order must be rewritten daily for multiday dosing.
Credit Hours: 1.4
c. A certain part of the drug's name should be italicized
Passing Score: 80%
or bolded.
Test ID#: 04-31/5-14
d. Trailing zeros must not be included in the written or-
Test Processing Fee: $15
The Oncology Nursing Society is accredited as a provider
Vincristine sulfate may be given by what route(s) of ad-
of continuing education in nursing by the
American Nurses Credentialing Center's Commission on
a. IV and intrathecal
b. Subcutaneous and intraventricular
California Board of Nursing, Provider #2850.
c. Intraventricular only
d. IV only
CE Test Questions
When administering vincristine sulfate via IV, which of
the following is the most important precaution to take to
11. Vincristine sulfate exerts its antitumor effect by
decrease the risk of extravasation?
a. Stabilizing the mitotic spindles, thus preventing cell
a. Teach the patient about ways to prevent and detect an
b. Preventing the synthesis of proteins essential for cell
b. Use an infusion pump to detect pressure changes in the
blood vessel.
c. Interfering with microtubule formation during meta-
c. Assess the patient for signs of extravasation only af-
ter the infusion is complete.
d. Altering the replication of DNA during the synthesis
d. Monitor for numbness and tingling in the patient's
hands and feet.
12. Once administered, vincristine sulfate is
What intervention currently is recommended after inad-
a. Taken up and tightly bound in the tissues.
vertent extravasation or injection of vincristine sulfate
b. Largely excreted in the urine within two hours.
into the muscle?
c. Distributed through the body over the next 90 minutes.
a. Subcutaneous infiltration with saline
d. Eliminated in small amounts (20%) in the feces.
b. Subcutaneous infiltration with hydrocortisone
13. A patient who is receiving vincristine sulfate as a part of the
c. Warm compresses
cancer treatment complains of abdominal pain and consti-
d. Cold compresses
pation. What is the most likely reason for these symptoms?
What strategies have been tried to prevent "wrong drug"
a. Lack of exercise
errors when vincristine sulfate is ordered?
b. Peripheral neuropathy
a. The order must be rewritten daily for multiday dosing.
c. Brain metastasis
b. Do not stock the drug close to others that look simi-
d. Autonomic dysfunction
lar and have a similar-sounding name.
14. What is the usual maximum adult dose of vincristine sul-
c. The prepared drug should not be delivered with other
a. 1 mg
d. Dye should be added so that the drug is a different color.
b. 1.4 mg
Inadvertent intrathecal administration of vincristine sul-
c. 2 mg
fate most commonly has occurred when
d. 2.8 mg
a. The person preparing the vincristine confused it with
15. Vincristine sulfate overdoses have been attributed to
another drug with a similar-sounding name.
a. Verbal orders that are not adequately verified.
b. The vincristine syringe was confused with another sy-
b. Administration of the drug by the wrong route.
ringe containing a drug to be given intrathecally.
c. Unclear decimal points in the written order.
c. The intrathecal vincristine accidently was administered
d. Administering the drug dose too rapidly.
to a different patient with a similar-sounding name.
16. What would you monitor for in a person who has re-
d. The vincristine was prepared as an infusion instead of
ceived an overdose of vincristine sulfate?
in a syringe for IV administration.
a. Restlessness
When assessing a person who was inadvertently given in-
b. Dilute urine
trathecal vincristine sulfate, what early symptom would
c. Bradycardia
you expect to find?
d. Difficulty swallowing
a. Diarrhea
17. When developing a policy to prevent vincristine sulfate
b. Decreased urine output
overdose, what would be most important to include?
c. Coma
a. The drug must be diluted and given as a short-term in-
d. Tremors
14. Ready-to-use doses of vincristine sulfate prepared by
15. A policy designed to decrease the risk of accidental in-
manufacturers and pharmacies in the United States must
trathecal administration of vincristine sulfate most likely
meet what requirement?
would include what measure?
a. They must be placed in an overwrap containing a spe-
a. A certain portion of the name vincristine sulfate
cific cautionary statement.
should be italicized or bolded on the label.
b. They must be diluted in at least 10 ml of normal sa-
b. Syringes containing intrathecal drugs and IV drugs
should not be delivered together.
c. They must include information about an antidote in
c. The vincristine sulfate must be diluted in 50 ml of
case of intrathecal administration.
normal saline and given as a short infusion.
d. They must include a label stating FOR INTRAVEN-
d. Dye should be added so that drugs prepared for in-
trathecal administration can be differentiated easily.
Oncology Nursing Forum Answer/Enrollment Form
Preventing Vincristine Sulfate Medication Errors (Test ID #04-31/5-14)
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