Yes

Antineoplastic Agent, Natural Source (Plant) Derivative

Treatment of leukemias, Hodgkin's disease, non-Hodgkin's lymphomas, Wilms' tumor, neuroblastoma, rhabdomyosarcoma

D

Hypersensitivity to vincristine or any component; for I.V. use only, fatal if given intrathecally; patients with demyelinating form of Charcot-Marie-Tooth syndrome

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 radiation.

>10%:

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

Vesicant chemotherapy

1% to 10%:

Cardiovascular: Orthostatic hypotension or hypertension, hypertension, hypotension

Central nervous system: Motor difficulties, seizures, headache, CNS depression, cranial nerve paralysis, fever

Dermatologic: Rash

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%)

Local: Phlebitis

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 irradiation.

Neuromuscular & skeletal: Jaw pain, leg pain, myalgia, cramping, numbness, weakness

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 "wrist drop"

Ocular: Photophobia

<1%: Stomatitis

Myelosuppressive: Occasionally mild leukopenia and thrombocytopenia may occur

WBC: Rare

Platelets: Rare

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

Increased toxicity:

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 (4°C)

Compatible with bleomycin, cytarabine, doxorubicin, fluorouracil, methotrexate, metoclopramide

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 reactions

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 mg

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 dose

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

May cause sedation, confusion, depression, or insomnia

May cause myelosuppression; use caution with clozapine and carbamazepine

No information available to require special precautions

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 not recommended.

Observe for life-threatening bronchospasm after administration; use of rectal thermometer or rectal tubing should be avoided to prevent injury to rectal mucosa

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)

Ahn YS, Harrington WJ, Mylvaganam R, et al, "Slow Infusion of Vinca Alkaloids in the Treatment of Idiopathic Thrombocytopenic Purpura," Ann Intern Med, 1984, 100(2):192-6.

Camplejohn RS, "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.

Igarashi M, Thompson EI, and Rivera GK, "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, 1988, 84(6):1016-22.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Joel S, "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.

Legha SS, "Vincristine Neurotoxicity. Pathophysiology and Management," Med 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.

Woods WG, O'Leary M, and Nesbit ME, "Life-Threatening Neuropathy and Hepatotoxicity in Infants During Induction Therapy for Acute Lymphoblastic Leukemia," J Pediatr, 1981, 98(4):642-5.