1 ML vincristine sulfate 1 MG/ML Injection [Vincasar]

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.

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 . A 50% reduction in the dose of Vincristine Sulfate Injection is recommended for patients having a direct serum bilirubin value above 3 mg/100 mL. The drug is administered intravenously at weekly intervals. TO REDUCE THE POTENTIAL FOR FATAL MEDICATION ERRORS DUE TO INCORRECT ROUTE OF ADMINISTRATION, VINCRISTINE SULFATE INJECTION SHOULD BE DILUTED IN A FLEXIBLE PLASTIC CONTAINER AND PROMINENTLY LABELED AS INDICATED FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES (See WARNINGS ). The concentration of Vincristine Sulfate Injection is 1 mg/mL. Do not add extra fluid to the vial prior to removal of the dose. Withdraw the solution of Vincristine Sulfate Injection into an accurate dry syringe, measuring the dose carefully. Do not add extra fluid to the vial in an attempt to empty it completely. Preparation for flexible plastic container Vincristine Sulfate Injection when diluted with 0.9% Sodium Chloride Injection in concentrations from 0.0015 mg/mL to 0.08 mg/mL is stable for up to 24 hours when protected from light or 8 hours under normal light at 25°C. Caution: 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. Local injection of hyaluronidase and the application of moderate heat to the area of leakage will help disperse the drug and may minimize discomfort and the possibility of cellulitis. Vincristine Sulfate Injection must be administered via an intact, free–flowing intravenous needle or catheter. Care should be taken that there is no leakage or swelling occurring during administration (see boxed WARNINGS ). The diluted Vincristine Sulfate Injection may be infused via a flexible plastic container directly into an intravenous catheter/needle or into a running intravenous infusion (see Drug Interactions below). Patients Receiving Radiation Therapy Vincristine Sulfate Injection should not be given to patients while they are receiving radiation therapy through ports that include the liver. When Vincristine Sulfate Injection is used in combination with L–asparaginase, Vincristine Sulfate Injection should be given 12 to 24 hours before administration of the enzyme in order to minimize toxicity; administering L–asparaginase before Vincristine Sulfate Injection may reduce hepatic clearance of vincristine. Drug Interactions Vincristine Sulfate Injection should not be diluted in solutions that raise or lower the pH outside the range of 3.5 to 5.5. It should not be mixed with anything other than 0.9% Sodium Chloride Injection USP. Whenever solution and container permit, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Handling and Disposal Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

WARNINGS This preparation is for intravenous use only. It should be administered by individuals experienced in the administration of Vincristine Sulfate Injection. The intrathecal administration of Vincristine Sulfate Injection usually results in death. To reduce the potential for fatal medication errors due to incorrect route of administration, Vincristine Sulfate Injection should be diluted in a flexible plastic container and prominently labeled as indicated "FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES." See OVERDOSAGE section for the treatment of patients given intrathecal Vincristine Sulfate Injection. Pregnancy Vincristine sulfate can cause fetal harm when administered to a pregnant woman. When pregnant mice and hamsters were given doses of vincristine sulfate that caused resorption of 23% to 85% of fetuses, fetal malformations were produced in those that survived. Five monkeys were given single doses of vincristine sulfate between days 27 and 34 of their pregnancies; 3 of the fetuses were normal at term, and 2 viable fetuses had grossly evident malformations at term. In several animal species, vincristine sulfate can induce teratogenesis as well as embryo death at doses that are nontoxic to the pregnant animal. There are no adequate and well–controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential hazard to the fetus. Women of child–bearing potential should be advised to avoid becoming pregnant.

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 .

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, 2.3 hours, and 85 hours respectively; however, the range of the terminal half–life in humans is from 19 to 155 hours. The liver is the major excretory organ in humans and animals. The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes (see PRECAUTIONS ). About 80% of an injected dose of vincristine sulfate appears in the feces and 10% to 20% can be found in the urine. Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound. Current principles of cancer chemotherapy involve the simultaneous use of several agents. Generally, each agent used has a unique toxicity and mechanism of action so that therapeutic enhancement occurs without additive toxicity. It is rarely possible to achieve equally good results with single–agent methods of treatment. Thus, vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone–marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy). See DOSAGE AND ADMINISTRATION section for possible increased toxicity when used in combination therapy.