Vincristine Sulfate IV injection is used in the treatment of acute leukemia. It is also commonly used in combination with other anticancer agents for the treatment of various malignancies, including Hodgkin’s disease, non-Hodgkin’s lymphomas (such as lymphocytic, mixed-cell, histiocytic, undifferentiated, nodular, and diffuse types), rhabdomyosarcoma, neuroblastoma, and Wilms’ tumor.

Vincristine Sulfate is an alkaloid derived from the periwinkle plant (Vinca rosea). It appears as a white to slightly yellow powder that is highly soluble in water and slightly soluble in alcohol. After intravenous administration, it follows a triphasic elimination pattern with half-lives of approximately 5 minutes (initial), 2.3 hours (intermediate), and about 85 hours (terminal), although the terminal half-life may vary widely. The drug is rapidly distributed into body tissues within 15–30 minutes after injection, where it binds strongly but reversibly. The liver plays a major role in elimination, with approximately 80% excreted in feces and 10–20% in urine.

Extreme care must be used in calculating and administering the dose of vincristine, since overdosage may have a very serious or fatal outcome. The drug is given i.v. at weekly intervals. Fatal if given intrathecally.

Adults: The usual dose of vincristine is 1.4 mg/m2.

Children: The usual dose of vincristine is 1.5–2 mg/m2. For children weighing 10 kg or less, the initial dose of vincristine should be 0.05 mg/kg once a week, with careful increasing of dosing thereafter based on effects. Vincristine should not be administered to patients receiving radiation therapy through ports that include the liver. When vincristine is used in combination with L-asparaginase, it should be given 12 to 24 hours prior to administration of the enzyme in order to minimize toxicity because L-asparaginase may reduce hepatic clearance of vincristine. Or, as directed by the registered physician.

Administration: Vincristine solution may be injected either directly into a vein or into the tubing of an i.g. infusion. Injection of the solution may be completed in about 1 minute. Further dilution: The solution may be further diluted with 0.9% sodium chloride injection or 0.5% dextrose injection if desired.

Allopurinol may increase the risk of bone marrow suppression caused by cytotoxic therapy, although the exact mechanism is not fully understood. The neurotoxic effects of vincristine may be enhanced when used with drugs such as asparaginase, isoniazid, or other agents affecting the peripheral nervous system. Concurrent use of vincristine with doxorubicin and prednisone may result in increased myelosuppression, and this combination should generally be avoided. Vincristine may also increase the uptake of methotrexate by cancer cells, a property utilized in high-dose methotrexate therapy.

Vincristine sulfate is contraindicated in patients with the demyelinating form of Charcot-Marie-Tooth syndrome. It should not be administered to patients receiving radiation therapy involving the liver. Patients with known hypersensitivity to vinca alkaloids or mannitol should not receive this drug.

Prior to the use of this drug, patients and/or parents/guardians 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. The following adverse reactions have been reported:

Hypersensitivity: Rare cases of allergic-type reactions, such as anaphylaxis, rash, and oedema, that are temporally related to vincristine therapy have been reported in patients receiving vincristine as part of multidrug chemotherapy regimens.

Gastrointestinal: Autonomic toxicity such as constipation and paralytic ileus are not uncommon and are frequently associated with abdominal cramps. Stool softeners, mild laxatives and enemas may be helpful. A routine prophylactic regimen of laxatives and enemas is usually recommended for patients receiving vincristine. Constipation may take the form of upper colon impaction, and on physical examination, the rectum may be empty. Colicky abdominal pain coupled with an empty rectum may mislead the physician.

Genitourinary/Hyperuricaemia: Hyperuricaemia may occur in some patients receiving vincristine, especially those with non-Hodgkin's lymphomas or leukaemia. In some patients, uric acid nephropathy may result. These effects may be minimised by adequate hydration, alkalinisation of the urine and/or administration of allopurinol. Polyuria, dysuria, and urinary retention due to bladder atony have occurred.

Cardiovascular: Hypertension and hypotension have occurred. Chemotherapy combinations that have included vincristine sulfate, when given to patients previously treated with mediastinal radiation, have been associated with coronary artery disease and myocardial infarction. Causality has not been established.

Neurologic: Frequently, there is a sequence to the development of neuromuscular side effects. Initially, only sensory impairment and paraesthesiae may be encountered. With continued treatment, neuritic pain and later motor difficulties may occur. There have been no reports of any agent that can reverse the neuromuscular manifestations that may accompany therapy with vincristine.

Other: Fever and headache have occurred. Other side effects include defective sweating, myoclonic jerks, abnormal Valsalva response, impotence and diminished libido. Weight loss has been reported at high doses.

Vincristine is classified as Pregnancy Category D and may cause harm to the fetus. There are no adequate controlled studies in pregnant women.The drug has been detected in human milk; therefore, breastfeeding should be avoided during treatment.

It is essential to ensure that the needle is correctly placed within the vein before administering vincristine. Accidental leakage into surrounding tissues during intravenous administration can lead to significant irritation. If extravasation occurs, the injection should be stopped immediately, and the remaining dose should be administered into another vein. Local administration of hyaluronidase along with the application of moderate heat to the affected area may help disperse the drug and reduce discomfort as well as the risk of cellulitis. Vincristine should be administered only by physicians experienced in cytotoxic chemotherapy. The drug is highly irritating and must not be given intramuscularly, subcutaneously, or intrathecally. Intrathecal administration is usually fatal. Management following accidental intrathecal administration has included immediate removal of cerebrospinal fluid and flushing with Lactated Ringer’s solution or other fluids; however, such measures have generally failed to prevent ascending paralysis and death. In one reported case, progressive paralysis was halted when immediate treatment was initiated after intrathecal exposure. Vincristine is a vesicant and may cause severe local tissue damage upon extravasation. If leakage occurs, administration should be stopped and the remaining dose given through another vein. Local injection of hyaluronidase combined with heat application may assist in drug dispersion and reduce tissue injury.

Leucopenia is less common with vincristine compared to other anticancer agents. However, caution is advised in patients with a history of gout or uric acid kidney stones, as acute uric acid nephropathy has been reported. Due to its limited penetration across the blood-brain barrier, additional therapeutic approaches may be required for central nervous system leukemia. The neurotoxic effects of vincristine may be enhanced when combined with other neurotoxic agents, spinal irradiation, or existing neurological disorders. Careful monitoring of dosage and neurological side effects is necessary, particularly in patients with prior cytotoxic therapy, radiation exposure, or pre-existing neuromuscular conditions. Acute dyspnea and severe bronchospasm have been reported following administration of vinca alkaloids, especially when used with mitomycin. These reactions may require intensive management, particularly in patients with pre-existing lung disease. In such cases, vincristine should not be administered again.

Cytotoxic chemotherapy

Store in a refrigerator at 2°C–8°C. Do not freeze. Protect from light. Keep out of reach of children.