|Oncovin® Injection; Vincasar®
LCR; Leurocristine; VCR; Vincristine Sulfate|
Antineoplastic Agent, Natural Source (Plant) Derivative
Treatment of leukemias, Hodgkin's disease, non-Hodgkin's lymphomas, Wilms'
tumor, neuroblastoma, rhabdomyosarcoma
Hypersensitivity to vincristine or any component; for I.V. use only,
fatal if given intrathecally; patients with demyelinating form of
The U.S. Food and Drug Administration (FDA) currently recommends that
procedures for proper handling and disposal of antineoplastic agents be
considered. Dosage modification required in patients with impaired hepatic
function or who have pre-existing neuromuscular disease; avoid extravasation;
use with caution in the elderly; avoid eye contamination; observe closely for
shortness of breath, bronchospasm, especially in patients treated with mitomycin
C. For I.V. use only; intrathecal administration results in death;
administer allopurinol to prevent uric acid nephropathy; not to be used with
Dermatologic: Alopecia occurs in 20% to 70% of patients
Extravasation: VCR is a vesicant and can cause tissue irritation and necrosis
if infiltrated; if extravasation occurs, follow institutional policy, which may
include hyaluronidase and hot compresses
1% to 10%:
Cardiovascular: Orthostatic hypotension or hypertension, hypertension,
Central nervous system: Motor difficulties, seizures, headache, CNS
depression, cranial nerve paralysis, fever
Endocrine & metabolic: Hyperuricemia
SIADH: Rarely occurs, but may be related to the neurologic toxicity; may
cause symptomatic hyponatremia with seizures; the increase in serum ADH
concentration usually subsides within 2-3 days after onset
Gastrointestinal: Constipation and possible paralytic ileus secondary to
neurologic toxicity; oral ulceration, abdominal cramps, anorexia, metallic
taste, bloating, nausea, vomiting, weight loss, diarrhea
Emetic potential: Low (<10%)
Neurologic: Alterations in mental status such as depression, confusion, or
insomnia; constipation, paralytic ileus, and urinary tract disturbances may
occur. All patients should be on a prophylactic bowel management regimen.
Cranial nerve palsies, headaches, jaw pain, optic atrophy with blindness have
been reported. Intrathecal administration of VCR has uniformly caused death; VCR
should never be administered by this route. Neurologic effects of VCR
may be additive with those of other neurotoxic agents and spinal cord
Neuromuscular & skeletal: Jaw pain, leg pain, myalgia, cramping,
Peripheral neuropathy: Frequently the dose-limiting toxicity of VCR. Most
frequent in patients >40 years of age; occurs usually after an average of 3
weekly doses, but may occur after just one dose. Manifested as loss of the deep
tendon reflexes in the lower extremities, numbness, tingling, pain, paresthesias
of the fingers and toes (stocking glove sensation), and "foot drop" or
Myelosuppressive: Occasionally mild leukopenia and thrombocytopenia may occur
Onset (days): 7
Nadir (days): 10
Recovery (days): 21
Symptoms of overdose include bone marrow suppression, mental depression,
paresthesia, loss of deep reflexes, alopecia, nausea, severe symptoms may occur
with 3-4 mg/m2
There are no antidotes for vincristine; treatment is supportive and
symptomatic, including fluid restriction or hypertonic saline (3% sodium
chloride) for drug-induced secretion of inappropriate antidiuretic hormone
(SIADH), diazepam or phenytoin for seizures, laxatives for constipation, and
antiemetics for toxic emesis; case reports suggest that folinic acid may be
helpful in treating vincristine overdose; it is suggested that 100 mg folinic
acid be given I.V. every 3 hours for 24 hours, then every 6 hours for 48 hours;
this is in addition to supportive care; the use of pyridoxine, leucovorin
factor, cyanocobalamin or thiamine have been used with little success for
drug-induced peripheral neuropathy
CYP3A3/4 and 3A5-7 enzyme substrate; CYP2D6 enzyme inhibitor
Digoxin plasma levels and renal excretion may decrease with combination
chemotherapy including vincristine
Vincristine should be given 12-24 hours before asparaginase to minimize
toxicity (may decrease the hepatic clearance of vincristine)
Acute pulmonary reactions may occur with mitomycin-C. Previous or
simultaneous use with mitomycin-C has resulted in acute shortness of breath and
severe bronchospasm within minutes or several hours after vinca alkaloid
injection and may occur up to 2 weeks after the dose of mitomycin.
Store intact vials at refrigeration (2°C to
8°C); stable for one month at room temperature
Further dilution in NS or D5W is stable for 21 days at room
temperature (25°C) and refrigeration
Compatible with bleomycin, cytarabine, doxorubicin, fluorouracil,
Standard I.V. dilution:
I.V. push: Dose/syringe (concentration = 1 mg/mL)
Maximum syringe size for IVP is 30 mL syringe and syringe should be less than
or equal to 75% full
IVPB: Dose/50 mL D5W
Binds to microtubular protein of the mitotic spindle causing metaphase
arrest; cell-cycle phase specific in the M and S phases
Absorption: Oral: Poor
Distribution: Poor penetration into the CSF; rapidly removed from the
bloodstream and tightly bound to tissues; penetrates blood-brain barrier poorly
Protein binding: 75%
Metabolism: Extensively in the liver
Half-life: Terminal: 24 hours
Elimination: Primarily in the bile (~80%); <1% excreted unchanged in urine
Refer to individual protocols as dosages vary with protocol used; adjustments
are made depending upon clinical and hematological response and upon adverse
Children >10 kg or BSA greater than or equal to 1 m2: 1-2
mg/m2, may repeat once weekly for 3-6 weeks; maximum single dose: 2
Neuroblastoma: I.V. continuous infusion with doxorubicin: 1
mg/m2/day for 72 hours
Adults: I.V.: 0.4-1.4 mg/m2 (up to 2 mg maximum in most patients);
may repeat every week
Dosing adjustment in hepatic impairment:
Serum bilirubin 1.5-3.0 mg/dL or AST 60-180 units: Administer 50% of normal
Serum bilirubin 3.0-5.0 mg/dL: Administer 25% of dose
Serum bilirubin >5.0 mg/dL or AST >180 units: Omit dose
The average total dose per course of treatment should be around 2-2.5 mg;
some recommend capping the dose at 2 mg maximum to reduce toxicity; however, it
is felt that this measure can reduce the efficacy of the drug
Serum electrolytes (sodium), hepatic function tests, neurologic examination,
CBC, serum uric acid
|Mental Health: Effects
on Mental Status|
May cause sedation, confusion, depression, or insomnia
Effects on Psychiatric
May cause myelosuppression; use caution with clozapine and
|Dental Health: Local
No information available to require special precautions
Effects on Dental Treatment|
No effects or complications reported
This medication can only be administered by infusion, usually on a cyclic
basis. Maintain adequate hydration (2-3 L/day of fluids unless instructed to
restrict fluid intake) and nutrition (small frequent meals will help). You will
most likely loss your hair (will grow back after therapy); experience
constipation (request medication); or feel weak or lethargic (use caution when
driving or engaging in tasks requiring alertness until response to drug is
known). Use good oral care to reduce incidence of mouth sores. You will be more
susceptible to infection; avoid crowds or exposure to infection. Report pain,
numbness, or tingling in fingers or toes (use care to prevent injury);
alterations in mental status (eg, confusion, insomnia, headaches, jaw pain, loss
of vision); signs of infection (eg, fever, chills, sore throat, burning
urination, fatigue); unusual bleeding (eg, tarry stools, easy bruising, or blood
in stool, urine, or mouth), unresolved mouth sores; skin rash or itching;
nausea; vomiting; abdominal pain; bloating; or difficulty breathing.
Pregnancy/breast-feeding precautions: Do not get pregnant. Breast-feeding is
Observe for life-threatening bronchospasm after administration; use of rectal
thermometer or rectal tubing should be avoided to prevent injury to rectal
Mix 250 units hyaluronidase with 6 mL of NS
Inject the hyaluronidase solution subcutaneously through 6 clockwise
injections into the infiltrated area using a 25-gauge needle; change the needle
with each new injection
Apply heat immediately for 1 hour; repeat 4 times/day for 3-5 days
Application of cold or hydrocortisone is contraindicated
Injection, as sulfate: 1 mg/mL (1 mL, 2 mL, 5 mL)
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"Slow Infusion of Vinca Alkaloids in the Treatment of Idiopathic Thrombocytopenic Purpura,"
Ann Intern Med, 1984, 100(2):192-6.
"A Critical Review of the Use of Vincristine (VCR) as a Tumour Cell Synchronizing Agent in Cancer Therapy,"
Cell Tissue Kinet, 1980, 13(3):327-35.
Crom WR, deGraaf SS, Synold T, et al,
"Pharmacokinetics of Vincristine in Children and Adolescents With Acute Lymphocytic Leukemia,"
J Pediatr, 1994, 125(4):642-9.
Dyke RW, "Treatment of Inadvertent Intrathecal Injection of Vincristine,"
N Engl J Med, 1989, 321(18):1270-1.
Ghosh K, Sivakumaran M, Murphy P, et al,
"Visual Hallucinations Following Treatment With Vincristine," Clin Lab
Haematol, 1994, 16(4):355-7.
Grush OC and Morgan SK, "Folinic Acid Rescue for Vincristine Toxicity,"
Clin Toxicol, 1974, 14(1):71-8.
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"Vincristine Neuropathy in Type I and Type II Charcot-Marie-Tooth Disease (Hereditary Motor Sensory Neuropathy),"
Med Pediatr Oncol, 1995, 25(2):113-6.
Jackson DV, Wells HB, Atkins JN, et al,
"Amelioration of Vincristine Neurotoxicity by Glutamic Acid," Am J Med,
Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure.
"The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding,"
January 12, 1987.
"The Comparative Clinical Pharmacology of Vincristine and Vindesine: Does Vindesine Offer Any Advantage in Clinical Use?"
Cancer Treat Rev, 1996, 21(6):513-25.
Kanwar VS, Albuquerque MLC, Ribeiro RC, et al,
"Veno-Occlusive Disease of the Liver After Chemotherapy for Rhabdomyosarcoma: Case Report With a Review of the Literature,"
Med Pediatr Oncol, 1995, 24(5):334-40.
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Toxicol, 1986, 1(6):421-7.
Perez Payarols J, Pardo Masferrer J, and Gomez Bellvert C,
"Treatment of Life-Threatening Infantile Hemangiomas With Vincristine," N
Engl J Med, 1995, 333(1):69.
Rodrigues RL, "Pharmacology and Toxicology of Chemotherapeutic Agents,"
Emerg Med Clin North Am, 1993, 11(2):431-43.
Tajti J, Somogyi I, and Szilard J,
"Treatment of Chronic Pain Syndromes With Transcutaneous Iontophoresis of Vinca Alkaloids, With Special Regard to Postherpetic Neuralgia,"
Acta Med Hung, 1989, 46(1):3-12.
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J Pediatr, 1981, 98(4):642-5.
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