Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

TUBULIN-BINDING AGENTS
following administration of vincristine showed normal
aggregation in vitro. Similarly, clot retraction and buccal
mucosal bleeding time were normal in vincristine-treated
dogs. Vincristine is not believed to have major effects
on wound healing.
Formulations and dose rates
Vincristine must be stored at 2–8°C to maintain potency and will
degrade if exposed to light.
DOGS
• 0.5–0.75 mg/m 2 IV bolus, once weekly or according to protocol
being used
• Doses as low as 0.02 mg/kg have been used to stimulate
platelet production
CATS
• 0.025 mg/kg or 0.5 mg/m 2 IV bolus, once weekly or according
to protocol being used
FERRETS
• 0.75 mg/m 2 IV bolus
Vincristine should never be administered
intrathecally.
Pharmacokinetics
In normal dogs, the disappearance of tritiated vincristine
from the plasma is biphasic, with an initial t 1/2 of
13 min and a second-phase t 1/2 of 75 min. Highest tissue
levels achieved are in spleen (2.28 ng/g tissue). Levels in
brain and cerebrospinal fluid are undetectable. Hepatic
metabolism and rapid biliary excretion are followed by
70% of administered drug being excreted in feces. Only
15% of the drug is excreted in urine. Oral absorption
is poor.
Adverse effects
● Vincristine should never be administered intrathecally.
● Myelosuppression is rarely reported when vincristine
is used as a single agent in dogs. However, neutropenia
is sporadically severe in cats 4–9 days following
drug administration.
● Like any chemotherapy drug, vincristine can cause
gastrointestinal signs. Anorexia seems to be most
common in the cat and vomiting in the dog.
● Neutropenia can occur in susceptible dogs, e.g.
certain collies, due to a mutation in the canine MDR1
gene causing a P-glycoprotein defect which also
confers susceptibility to toxic effects of ivermectin.
● Vincristine is not believed to have major effects on
wound healing.
● Constipation is reported to occur in both dogs and
cats following administration of vincristine, but
appears more common in cats.
● In humans, the dose-limiting toxicity of vincristine is
a peripheral neuropathy. The effects are believed to
be limited to peripheral nerves because vincristine
does not penetrate the blood–brain barrier. Vincristine
interrupts microtubular function, resulting in an
inability to maintain axonal membrane integrity.
Dogs appear to be relatively resistant to the neuropathic
effect of vincristine, but a single case has been
reported following 16 weekly doses of 0.5 mg/m 2 .
● Extravasation of vincristine during infusion results
in local tissue necrosis and sloughing. If extravasation
is suspected, the infusion should be immediately
discontinued but the infusion catheter left in place
and an attempt made to aspirate fluid from the site
to decrease the remaining drug. Warm compresses
should be applied to the area for 15 min q.6 h for
3 d. The author also applies a solution (Synotic®)
containing dimethyl sulfoxide, fluocinolone acetonide
and flunixin meglamine (1 mL per Synotic® vial)
applied topically q.12 h for 3–5 days following drug
extravasation. Owners should wear gloves when
applying the solution.
● Hyaluronidase has been reported to decrease the
tissue damage following vincristine extravasation.
300 U of hyaluronidase are injected into the catheter,
if still present, or into the indurated area in six aliquots
using a 25-gauge needle. The injection may be
repeated weekly.
● Administration of vincristine changes the morphology
of bone marrow cells within 24 h of administration.
The predominant changes are seen in erythroid
cells. Abnormalities included increased numbers of
cells in metaphase, fragmented nuclei and atypical
nuclear configurations. An increased M : E ratio was
seen 24 h post-vincristine.
Known drug interactions
The manufacturer’s recommendations indicate that vincristine
should not be given in combination with l-
asparaginase because of severe myelosuppression;
consequently some veterinary oncologists recommend
spacing drug administration by 12–48 h. Neutropenia
is seen in up to 50% of dogs at some centers treated
with l-asparaginase and vincristine, although it rarely
results in clinical signs. In one study which evaluated
147 dogs, neutropenia occurred in 40% of those receiving
the combination of drugs, irrespective of the interval
between administration of the two drugs. Hospitalization
was necessary in 16% of dogs.
Vinblastine
Other names
NSC-49842, vincaleukoblastine, VLB Velban, Velbe (Europe)
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