Vincristine Sulfate

A to Z Drug Facts

Actions Mode of action is unknown. In vitro, vincristine arrests mitotic division at metaphase. It reversibly binds to microtubule and spindle proteins in the S phase. Within 15 to 30 min following IV administration, more than 90% of the drug is distributed from blood into tissue where it remains tightly, but not irreversibly, bound. Penetration across the blood-brain barrier is poor. Studies show a triphasic serum decay pattern following rapid IV injection. Initial, middle, and terminal half-lives are 5 min, 5.3 hr, and 85 hr, respectively; the range of the terminal half-life is 19 to 155 hr. The liver is the major excretory organ; approximately 80% of a dose appears in feces and 10% to 20% in urine. Hepatic dysfunction may alter elimination kinetics and augment toxicity.

 Indications

Adult/Pediatric

Acute lymphocytic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, Wilms' tumor.

Small-cell lung carcinoma, brain tumors, multiple myeloma, Kaposi's sarcoma, chronic lymphocytic and myelocytic leukemias, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura.

 Contraindications Patients with demyelinating form of Charcot-Marie-Tooth syndrome.

 Route/Dosage

Acute Lymphocytic Leukemia, Lymphomas, Rhabdomyosarcoma, Neuroblastoma, Wilms' Tumor

ADULT: IV 1.4 mg/m² weekly (typical dose, 2 mg).

PEDIATRIC: IV Children weighing more than 10 kg (or body surface area at least 1 m²): 1.4 to 2 mg/m² weekly for 3 to 8 wk. Do not exceed a max of 2 mg/dose. Children weighing up to 10 kg (or body surface area less than 1 m²): 0.05 mg/kg weekly initially. Titrate dose as tolerated, up to a max of 2 mg/dose. Continue therapy for 3 to 8 wk.

Adjustment in Hepatic Insufficiency

ADULT: IV A 50% reduction in dose is recommended for patients having a direct serum bilirubin value more than 3 mg/dL.

Neuroblastoma, Combination Therapy

PEDIATRIC: IV Children weighing more than 10 kg (or body surface area at least 1 m²): Vincristine 1 mg/m²/day by continuous infusion over 24 hr for 3 days (total dose of 3 mg/m² over a 3-day period).

Interactions

CYP450 inhibitors

Vincristine elimination may be reduced by cytochrome P450 enzyme inhibitors.

Digoxin

May decrease digoxin plasma concentration.

Itraconazole

Vincristine neurotoxicity has occurred during coadministration.

L-asparaginase

Vincristine clearance may decrease when L-asparaginase is given prior to vincristine. Give vincristine 12 to 24 hr prior to L-asparaginase.

Mitomycin

Acute shortness of breath and severe bronchospasm have occurred following concomitant or previous use of mitomycin.

Phenytoin

May reduce phenytoin plasma concentration.

Quinolone antibiotics

Vincristine may decrease oral absorption of quinolone antibiotics.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypertension; hypotension; MI. CNS: Autonomic and peripheral neuropathy; headache. DERMATOLOGIC: Alopecia; rash GI: Mucositis; abdominal cramps; diarrhea; anorexia; intestinal necrosis or perforation; constipation that can lead to upper colon impaction; paralytic ileus; weight loss. GU: Amenorrhea; polyuria; dysuria; urinary retention because of bladder atony; azoospermia. HEMATOLOGIC: Bone marrow suppression; nadir less than 7 days. MUSCULOSKELETAL: Acute bone or jaw pain. RESPIRATORY: Acute shortness of breath; severe bronchospasm. SPECIALSENSES: Optic atrophy with blindness; transient cortical blindness; ptosis; diplopia; photophobia. OTHER: Fever.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Dosage adjustment (pediatric): Follow dosage adjustment guidelines recommended for adults. IV use only: Intrathecal use may result in death. Hypersensitivity reactions: Hypersensitivity temporally related to vincristine therapy has occurred. Extravasation risk: Local irritation or phlebitis may occur. Refer to your institution specific protocol. CNS leukemia: CNS leukemia has occurred. Additional agents may be required. Pulmonary reactions: Acute shortness of breath and severe bronchospasm have occurred, most frequently when the drug was used with mitomycin-C.

 Administration/Storage

• Refrigerate. Protect from light.
• Do not dilute vincristine for routine IV use. For continuous IV infusion, vincristine may be diluted with 0.9% Sodium Chloride or 5% Dextrose.
• Administer by IV injection or continuous IV infusion.
• Do not filter.
• Give over a 1-min period by IV push injection or IV side arm into a running infusion.
• Continuous infusions can only be administered through a central venous catheter resting in the vena cava. A peripherally-inserted central catheter, or PICC line, may also be appropriate.

 Assessment/Interventions

• Consider routine prophylaxis for constipation.
• Hyperuricemia may occur because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.
• Perform CBC before each dose.

 Patient/Family Education

• Explain name, action, and potential side effects of drug.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve max benefit possible.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver that medication may cause hair loss but that it is reversible when therapy is stopped.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; shortness of breath or difficulty breathing; abnormal skin sensations; stumbling; muscle wasting; fever, chills, or other signs of infection; redness or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, constipation, diarrhea, or appetite loss; persistent or worsening general body weakness.
• Instruct patient not to take any prescription or OTC medications or dietary supplements unless advised to do so by health care provider.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.
• Instruct women of childbearing potential to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Advise patient, family, or caregiver that following discharge, frequent follow-up visits and laboratory tests will be required to monitor therapy and to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts