Vincristine belongs to a group of drugs known as the vinca alkaloids. Vinca alkaloids are organic compounds made up of carbon, hydrogen, nitrogen, and oxygen that derive from the periwinkle plant. These drugs block cell growth by stopping mitosis by interfering with microtubule polymerization. Other drugs in this class approved for use in the United States include vinblastine and vinorelbine.[1][2]

The United States Food and Drug Administration (FDA) approved indications of vincristine are acute lymphocytic leukemia, lymphoid blast crisis of chronic myeloid leukemia and Hodgkin and Non-Hodgkin lymphoma. Vincristine also has several off-label uses that include central nervous system (CNS) tumors, Ewing sarcoma, gestational trophoblastic tumors, multiple myeloma, ovarian cancer, primary CNS lymphoma, small cell lung cancer, and advanced thymoma in adult patients.[3]

 FDA Approved indications in pediatric patients:

• Acute lymphocytic lymphoma (ALL)
• Burkitt lymphoma and B-cell ALL
• Hodgkin lymphoma
• Neuroblastoma
• Rhabdomyosarcoma
• Wilms tumor

 Off-label uses:

• Ewing sarcoma
• Medulloblastoma
• Retinoblastoma

Vincristine acts by binding to tubulin and inhibiting the formation of microtubules. This inhibition causes mitosis to arrest at metaphase, through the disruption of mitotic spindle formation, especially during the M and S phases. Another mechanism of action of vincristine includes interfering with nucleic acid and protein synthesis by blocking glutamic acid utilization.[4]

The nurse or other personnel who administers vincristine should ALWAYS check the label for the dose, duration, and route of administration. Administration of vincristine is NEVER an emergency; several fatal cases have resulted from administering vincristine via the wrong route or rapid rate.

Vincristine should be administered intravenously as a short 5 to 10-minute infusion. The Institute for Safe Medication Practices (ISMP) and the World Health Organization (WHO) strongly recommends vincristine be dispensed in a 25 to 50 ml mini bag. If the mini bag is not available, vincristine administration may be as a slow 1-minute intravenous push. Administration via any other routes may be fatal. For patients receiving medications intended for CNS administration, vincristine should be administered separately and not at the same time.[5]

Vincristine is a vesicant; therefore, proper caution needs to be taken to ensure correct needle or catheter placement prior to and during intravenous infusion to avoid extravasation. In instances where extravasation occurs, the infusion should be discontinued and disconnected immediately leaving the needle or cannula in place. The extravasated solution should then be gently aspirated ensuring the line is NOT flushed. Then the hyaluronidase antidote should be initiated, followed by the removal of the needle or cannula, and a warm, dry compression should be applied for 20 minutes 4 times a day on days 1 and 2 of extravasation. Lastly, reevaluation should occur and the remaining vincristine dose administered intravenously through a separate vein.[6][7]

 Metabolism

Vincristine is rapidly removed from the bloodstream and is tightly bound to tissues, but it poorly penetrates the blood-brain barrier. Vincristine undergoes extensive metabolism in the liver via CYP3A4. Patients with serum bilirubin levels > 3 mg/dl will require dose adjustments; per the manufacturer's label, the dose in such patients should be 50% of the normally administered dose. Vincristine is excreted primarily in the feces.[8]

The adverse effects caused by vincristine affects many systems in the body. Notable systems include: cardiovascular, CNS, dermatological, endocrine and metabolic, gastrointestinal, genitourinary, hepatic, renal, respiratory, neuromuscular, otic, and ophthalmic. Some adverse effects that can occur while administering vincristine based on body system include[9]:

Cardiovascular: Edema, hyper/hypotension, myocardial infarction, ischemic heart disease

Central nervous system: Coma, motor dysfunction, paralysis, neuralgia, peripheral neuropathy, sensory disturbances, dizziness, muscle impairment, decreased tendon reflex

Dermatological: Alopecia and skin rashes

Endocrine and metabolic: Hyperuricemia, weight loss, or uric acid nephropathy

Gastrointestinal system: Abdominal cramps, constipation, nausea, vomiting, sore throat, or intestinal necrosis

Genitourinary: Bladder dysfunction, urinary retention, or dysuria

Other adverse effects worth mentioning may include: 

Hematologic & oncologic: Anemia, hemolytic uremic syndrome, leukopenia, thrombocytopenia (mild), thrombotic thrombocytopenic purpuraHepatic: Hepatic sinusoidal obstruction syndrome Local: Local irritationNeuromuscular & skeletal: Back, limb and jaw pain, amyotrophy, myalgia, otalgiaOphthalmic: Blindness, nystagmus, optic atrophy with blindness

Adverse effects that may be less notable include: Deafness, polyuria, bronchospasm, dyspnea

Vincristine use is contraindicated in patients with demyelinating Charcot-Marie-Tooth syndrome. While documentation of allergenic cross-reactivity for drugs within this class is limited, due to the similarities in chemical structures and pharmacological actions, cross-sensitivity cannot be ruled out.[10]

US Boxed Warnings:

Experienced physician:

Administration of vincristine should be by individuals with experience in administering the drug.

Extravasation:

Intravenous (IV) needle or catheter must be in proper position before infusion or injection of any of the medication. Improper positioning may lead to leakage into the surrounding tissue during IV administration. Leakage may cause considerable irritation. Injection or infusion must be discontinued immediately if extravasation occurs. 

For IV use only:

Vincristine is indicated for IV use only. It is fatal if given by any other routes. Vincristine administered by intrathecal routes usually results in death.

All syringes containing vincristine must be labeled and have the provided auxiliary sticker attached. The auxiliary label must state; " For intravenous use only. Fatal if given by other routes."