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Vincristine should be used only by physicians experienced in cytotoxic chemotherapy.
Precautions for Administration: This preparation is for intravenous use only. Can be fatal if administered intrathecally (see Dosage & Administration and Contraindications).
Vincristine is very irritating and should not be given intramuscularly, subcutaneously or intrathecally. Intrathecal administration of vincristine is usually fatal. When dispensed, flexible plastic containers containing this product should be labelled: "WARNING - FOR INTRAVENOUS USE ONLY - FATAL IF GIVEN BY OTHER ROUTES."
Emergency Treatment of Accidental Intrathecal Administration: Treatment of patients following accidental intrathecal administration of vincristine has included immediate removal of spinal fluid and flushing with Lactated Ringer's solution, as well as other solutions, and has not prevented ascending paralysis and death. In one case, progressive paralysis in an adult was arrested by the following treatment initiated immediately after the intrathecal injection: 1. As much spinal fluid was removed as could be safely done through lumbar access.
2. The subarachnoid space was flushed with Lactated Ringer's solution infused continuously through a catheter in a cerebral lateral ventricle at the rate of 150 mL/hour. The fluid was removed through a lumbar access.
3. As soon as fresh frozen plasma became available, the fresh frozen plasma, 25 mL, diluted in 1 L of Lactated Ringer's solution was infused through the cerebral ventricular catheter at the rate of 75 mL/hour with removal through the lumbar access. The rate of infusion was adjusted to maintain a protein level in the spinal fluid of 150 mg/dL.
4. Glutamic acid, 10 grams was given intravenously over 24 hours followed by 500 mg 3 times daily by mouth for 1 month or until neurological dysfunction stabilised. The role of glutamic acid in this treatment is not certain and may not be essential.
Extravasation: Vincristine is a vesicant and may cause a severe local reaction on extravasation. If leakage into the surrounding tissue should occur during intravenous administration of vincristine, the infusion should be discontinued immediately and any remaining portion of the dose should be introduced into another vein. Local injection of hyaluronidase with the application of heat has been used to disperse the drug in order to minimise discomfort and the possibility of tissue damage.
Haematological: Leucopenia is less likely following therapy with vincristine than is the case with other oncolytic agents. However, because of its possibility of granulocytopenia both physician and patient should remain alert for signs of any complicating infection.
If leucopenia or a complicating infection is present, then administration of the next dose of vincristine warrants careful consideration.
Urate Nephrotoxicity: The risk/benefit should be considered in patients with a history of gout or urate renal stones, as acute uric acid nephropathy, which may occur after the administration of oncolytic agents, has also been reported with vincristine.
Treatment of Central Nervous System Leukaemia: As vincristine penetrates the blood-brain barrier poorly, additional agents and routes of administration may be required for central nervous system leukaemia. Vincristine must not be administered intrathecally.
The neurotoxic effect of vincristine may be additive with other neurotoxic agents or increased by spinal cord irradiation and neurological disease.
Neurotoxicity: Neurotoxicity is the most common dose-limiting side effect (see Adverse Reactions). The development of neuromuscular effects is generally sequential with initial sensory impairment and paraesthesiae. With further treatment neuritic pain may develop and, later, motor difficulties. There have been no reports of any agent that can reverse these neuromuscular manifestations. Exacerbation of pre-existing neurological disorders may occur. Discontinuation of treatment should be considered if neuromuscular effects continue to be a problem.
Particular attention should be given to dosage and neurologic side effects if vincristine is administered to patients who have had previous cytotoxic drug therapy or irradiation and in those with pre-existing neuromuscular disease (including sensory peripheral neuropathy and steroid-induced myopathy), and also when other drugs with neurotoxic potential are being used. The neurotoxic effect of vincristine may be additive with other neurotoxic agents or increased by spinal cord irradiation and neurological disease. Care should also be taken in elderly patients, who may be more susceptible to neurotoxicity (see Dosage & Administration).
Respiratory: 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 and may require aggressive treatment, particularly when there is pre-existing pulmonary dysfunction. The onset of these reactions may be within minutes or several hours after the vinca is intravenously administered and may occur up to 2 weeks following the dose of mitomycin. Progressive dyspnoea requiring chronic therapy may occur. Vincristine should not be readministered.
Patients who received vincristine sulfate chemotherapy in combination with anticancer drugs known to be carcinogenic have developed secondary malignancies. The contributing role of vincristine sulfate in this development has not been determined. No evidence of carcinogenicity was found following intraperitoneal administration of vincristine in rats and mice, although this study was limited.
Optic: Care should be taken to avoid accidental contamination of the eyes, because vincristine is highly irritant and can cause corneal ulceration. The eyes should be washed with water immediately and thoroughly.
Infection: The risks and benefits should be considered before vincristine is administered to patients with an infection, due to its immunosuppressive effects. It should be administered with caution to patients with herpes zoster or with existing or recent chickenpox (including recent exposure), as there is a risk of severe generalised disease developing.
Immunisation: Immunisation of patients being treated with vincristine should only be undertaken with extreme caution (see Interactions). People in close contact with the patient, especially family members, should postpone immunisation with oral polio vaccines.
Effects on laboratory tests: Because dose-limiting clinical toxicity is manifested as neurotoxicity, clinical evaluation (e.g., history, physical examination) is necessary to detect the need for dosage modification. Following administration of vincristine sulfate, some individuals may have a fall in the white-blood-cell count or platelet count, particularly when previous therapy or the disease itself has reduced bone-marrow function. Therefore, a complete blood count should be done before administration of each dose. Acute elevation of serum uric acid may also occur during induction of remission in acute leukaemia; thus, such levels should be determined frequently during the first 3 to 4 weeks of treatment or appropriate measures taken to prevent uric acid nephropathy (see Adverse Reactions). The laboratory performing these tests should be consulted for its range of normal values.
Hepatocellular dysfunction has been noted in some patients treated with vincristine. Liver function tests are therefore recommended when vincristine therapy is initiated and at periodic intervals during therapy, depending on the patient's clinical state, the dosage used and any concomitant therapy.
Effects on ability to drive and use machines: The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration. However, adverse effects of vincristine sulfate (with unknown frequency) may include dizziness, visual disturbances and neuromuscular effects which could affect the ability to drive or use machines. See Adverse Reactions.
Use in hepatic impairment: Because of the hepatic metabolism and biliary excretion of vincristine, a dosage reduction may be required in patients with liver disease or jaundice. An increase in the severity of side-effects may be experienced by patients with liver disease sufficient to decrease biliary excretion.
Use in renal impairment: No data available.
Use in Children: See Dosage & Administration.
Use in the elderly: See Dosage & Administration.
