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|Vincristine Sulfate

Vincristine Sulfate

Trade Names:
Oncovin
- Solution for Injection 1 mg/mL

Mechanism of Action

Pharmacology

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.

Pharmacokinetics

Absorption

Very rapidly absorbed via IV (15 to 30 min).

Distribution

More than 90% of drug is distributed from blood to tissue, where it remains tightly but not irreversibly. Penetration across the blood brain barrier is poor.

Metabolism

Triphasic serum decay following rapid IV injection.

Elimination

Terminal t _½ is 85 hr (19 to 155 hr). Liver is the major excretory organ. 80% of the dose appears in the feces, 10% to 20% in the urine.

Onset

15 to 30 min.

Special Populations

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

Indications and Usage

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

Unlabeled Uses

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

Contraindications

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

Dosage and Administration

IV 1.4 mg/m ² weekly (typical dose, 2 mg).

IV 1.4 to 2 mg/m ² weekly for 3 to 8 wk. Do not exceed a max of 2 mg/dose.

IV 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.

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

IV Vincristine 1 mg/m ² /day by continuous infusion over 24 hr for 3 days (total dose of 3 mg/m ² over a 3-day period).

General Advice

• 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.

Storage/Stability

Refrigerate. Protect from light.

Drug Interactions

Vincristine elimination may be reduced by cytochrome P450 enzyme inhibitors.

May decrease digoxin plasma concentration.

Vincristine neurotoxicity has occurred during coadministration.

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

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

May reduce phenytoin plasma concentration.

Vincristine may decrease oral absorption of quinolone antibiotics.

Laboratory Test Interactions

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.

Genitourinary

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.

Special Senses

Optic atrophy with blindness; transient cortical blindness; ptosis; diplopia; photophobia.

Miscellaneous

Fever.

Precautions

Pregnancy

Category D . Can cause fetal harm when administered to pregnant women.

Lactation

Undetermined.

Hypersensitivity

Hypersensitivity temporally related to vincristine therapy has occurred.

Dosage adjustment (pediatric)

Follow dosage adjustment guidelines recommended for adults.

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.

Overdosage

Symptoms

Side effects are dose-related. Expect exaggerated side effects.

Patient Information

• 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 breast-feeding.
• 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.