Vincristine

What it is used for

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.

How to take it

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.

Side effects, and when to stop

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. The severity of such reactions seems to increase when the calculated amount of drug is given in divided doses. Other adverse reactions, such as hair loss, sensory loss, paresthesia, difficulty in walking, slapping gait, loss of deep–tendon reflexes, and muscle wasting, may persist for at least as long as therapy is continued. Generalized sensorimotor dysfunction may become progressively more severe with continued treatment. Although most such symptoms usually disappear by about the sixth week after discontinuance of treatment, some neuromuscular difficulties may persist for prolonged periods in some patients. Regrowth of hair may occur while maintenance therapy continues.

The following adverse reactions have been reported:

Hepatic veno-occlusive disease has been reported in patients receiving vincristine, particularly in pediatric patients, as part of standard combination chemotherapy regimens. Some of the patients had fatal outcomes; some who survived had undergone liver transplantation.

Who should not take it

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.

Other medicines and 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.

Vincristine sulfate is a substrate for cytochrome P450 3A isozymes (CYP3A). Concurrent administration of vincristine sulfate with itraconazole or fluconazole (known inhibitors of the CYP3A metabolic pathway) has been reported to cause an earlier onset and/or an increased severity of neuromuscular side effects (see ADVERSE REACTIONS ). This interaction is presumed to be related to inhibition of the metabolism of vincristine. Therefore, the concomitant use of strong CYP3A inhibitors with vincristine sulfate should be avoided. Patients should be frequently monitored for adverse reactions with concomitant use of moderate CYP3A inhibitors (e.g., fluconazole) with vincristine sulfate.

Concurrent use of strong CYP3A inducers (e.g., St. John's Wort) with vincristine sulfate should be avoided.

Vincristine sulfate is also a substrate for P-glycoprotein (P-gp). Therefore, the concomitant use of P-gp inhibitors or inducers should be avoided.

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.

Storing it

This product should be refrigerated between 2°C–8°C (36°F–46°F). Discard unused solution. Protect from light. Store Upright.

General

Acute uric acid nephropathy, which may occur after the administration of oncolytic agents, has also been reported with vincristine sulfate. In the presence of leukopenia or a complicating infection, administration of the next dose of Vincristine Sulfate Injection warrants careful consideration. Treatment with vincristine sulfate in combination with other chemotherapy agents may cause myelosuppression. Monitor complete blood counts during treatment with vincristine sulfate (see Laboratory Tests below) and provide supportive care, including administration of hematopoietic growth factors, as clinically indicated.

If central nervous system leukemia is diagnosed, additional agents may be required, because vincristine does not appear to cross the blood–brain barrier in adequate amounts.

Particular attention should be given to dosage and neurologic side effects if Vincristine Sulfate Injection is administered to patients with preexisting neuromuscular disease and when other drugs with neurotoxic potential are also being used.

Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids. These reactions have been encountered most frequently when the vinca alkaloid was used in combination with mitomycin–C and may require aggressive treatment, particularly when there is preexisting pulmonary dysfunction. The onset of these reactions may occur minutes to several hours after the vinca alkaloid is injected and may occur up to 2 weeks following the dose of mitomycin. Progressive dyspnea requiring chronic therapy may occur. Vincristine sulfate should not be readministered.

Care must be taken to avoid contamination of the eye with concentration of Vincristine Sulfate Injection used clinically. If accidental contamination occurs severe irritation (or, if the drug was delivered under pressure, even corneal ulceration) may result. The eye should be washed immediately and thoroughly.

The safety of immunization with live vaccines during treatment with vincristine sulfate has not been studied and vaccination with a live virus is not recommended during treatment with vincristine sulfate. Follow current vaccination practice guidelines for administration of live vaccines for patients who have received chemotherapy after completion of treatment with vincristine sulfate.