Overview
DESCRIPTION Vincristine Sulfate Injection, USP is the salt of an alkaloid obtained from a common flowering herb, the periwinkle plant ( Vinca rosea Linn). Originally known as leurocristine, it has also been referred to as LCR and VCR. The molecular formula for Vincristine Sulfate, USP is C 46 H 56 N 4 O 10 ∙H 2 SO 4 . It has a molecular weight of 923.04.
Mechanism of Action
CLINICAL PHARMACOLOGY The mechanisms of action of vincristine sulfate remain under investigation. The mechanism of action of vincristine sulfate has been related to the inhibition of microtubule formation in mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Central nervous system leukemia has been reported in patients undergoing otherwise successful therapy with vincristine sulfate. This suggests that vincristine does not penetrate well into the cerebrospinal fluid. Pharmacokinetic studies in patients with cancer have shown a triphasic serum decay pattern following rapid intravenous injection. The initial, middle and terminal half–lives are 5 minutes, 2.
Indications
- INDICATIONS AND USAGE Vincristine Sulfate Injection is indicated in acute leukemia. Vincristine Sulfate Injection has also been shown to be useful in combination with other oncolytic agents in Hodgkin's disease, non–Hodgkin's malignant lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor.
Common Doses
- 2 mg
- 0.05 mg
- 1.4 mg
- 3 mg
Dosage
DOSAGE AND ADMINISTRATION This preparation is for intravenous use only (see WARNINGS ). Neurotoxicity appears to be dose related. Extreme care must be used in calculating and administering the dose of Vincristine Sulfate Injection since overdosage may have a very serious or fatal outcome. The usual dose of Vincristine Sulfate Injection for pediatric patients is 1.5–2 mg/m 2 . For pediatric patients weighing 10 kg or less, the starting dose should be 0.05 mg/kg, administered once a week. The usual dose of Vincristine Sulfate Injection for adults is 1.4 mg/m 2 .
Black Box Warning
WARNINGS Caution–This preparation should be administered by individuals experienced in the administration of Vincristine Sulfate Injection. It is extremely important that the intravenous needle or catheter be properly positioned before any vincristine is injected. Leakage into surrounding tissue during intravenous administration of Vincristine Sulfate Injection may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein.
Contraindications
- CONTRAINDICATIONS Patients with the demyelinating form of Charcot–Marie–Tooth syndrome should not be given Vincristine Sulfate Injection. Careful attention should be given to those conditions listed under WARNINGS and PRECAUTIONS .
Side Effects
- ADVERSE REACTIONS Prior to the use of this drug, patients and/or their parents/guardian should be advised of the possibility of untoward symptoms. In general, adverse reactions are reversible and are related to dosage. The most common adverse reaction is hair loss; the most troublesome adverse reactions are neuromuscular in origin. When single, weekly doses of the drug are employed, the adverse reactions of leukopenia, neuritic pain, and constipation occur but are usually of short duration (ie., less than 7 days). When the dosage is reduced, these reactions may lessen or disappear.
Interactions
- Drug Interactions The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. Dosage adjustment should be based on serial blood level monitoring. The contribution of vincristine sulfate to this interaction is not certain. The interaction may result from reduced absorption of phenytoin and an increase in the rate of its metabolism and elimination.