Vincristine

Article Author:
Jameshia Below
Article Editor:
Joe M Das
Updated:
1/1/2019 8:04:19 PM
PubMed Link:
Vincristine

Indications

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

Mechanism of Action

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]

Administration

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]

Adverse Effects

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

Contraindications

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." 

Monitoring

For patients that are on vincristine, several aspects should be monitored such as the infusion site, the patient’s neurological functions, and different laboratory values. Monitoring of laboratory values including serum electrolytes such as serum sodium, as well as serum uric acid, hepatic function, and a complete blood count with differential is required, as is monitoring for the signs and symptoms of peripheral neuropathy.

Enhancing Healthcare Team Outcomes

Since vincristine can result in a wide range of complications, it is imperative that health care professionals are educated and taking the precautions for proper administration. Vincristine should only be administered by individuals experienced in the administration of the drug.  Periodic lab tests and clinical examination should be used to monitor serum electrolytes, hepatic function, neurological examination, and to watch for signs and symptoms of peripheral neuropathy. Interprofessional teamwork and communication is key to providing success for all patients. All parties involved play a critical role in the care of cancer patients. The oncologist should ensure that oncology therapies are patient specific and selected after a thorough evaluation of the patient. They should also ensure that all healthcare providers involved are made aware of the monitoring parameters and potential adverse events.


References

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[2] Pernot B,Gyan E,Maillot F,Hodges P,Ertault M,Ferreira-Maldent N, Lymphomas diagnosed in an internal medicine department compared to lymphomas diagnosed in other departments: Clinical and outcome differences. Medicine. 2018 Nov     [PubMed PMID: 30461623]
[3] Schiller GJ,Damon LE,Coutre SE,Hsu P,Bhat G,Douer D, High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial. Journal of adolescent and young adult oncology. 2018 Oct     [PubMed PMID: 30239252]
[4] Martino E,Casamassima G,Castiglione S,Cellupica E,Pantalone S,Papagni F,Rui M,Siciliano AM,Collina S, Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead. Bioorganic     [PubMed PMID: 30122223]
[5] Beaver C, Vincristine Minibag Administration: A Quality Improvement Project to Minimize Medical Errors. Clinical journal of oncology nursing. 2018 Dec 1     [PubMed PMID: 30452001]
[6] Nurgat ZA,Smythe M,Al-Jedai A,Ewing S,Rasheed W,Belgaumi A,Ahmed SO,Ashour M,Al Agil A,Siddiqui K,Aljurf M, Introduction of vincristine mini-bags and an assessment of the subsequent risk of extravasation. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2015 Oct     [PubMed PMID: 24821691]
[7] Gilbar P,Chambers CR,Larizza M, Medication safety and the administration of intravenous vincristine: international survey of oncology pharmacists. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2015 Feb     [PubMed PMID: 24418800]
[8] Voorhorst MJ,van Maarseveen EM,van Lankveld AJ,Teske E, Bioavailability of cyclophosphamide and vincristine after intraperitoneal administration in cats. Anti-cancer drugs. 2014 Nov     [PubMed PMID: 25144346]
[9] Tsubaki M,Takeda T,Matsumoto M,Kato N,Yasuhara S,Koumoto YI,Imano M,Satou T,Nishida S, Tamoxifen suppresses paclitaxel-, vincristine-, and bortezomib-induced neuropathy via inhibition of the protein kinase C/extracellular signal-regulated kinase pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2018 Oct     [PubMed PMID: 30360692]
[10] Vaisheva F,Delbes G,Hales BF,Robaire B, Effects of the chemotherapeutic agents for non-Hodgkin lymphoma, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), on the male rat reproductive system and progeny outcome. Journal of andrology. 2007 Jul-Aug     [PubMed PMID: 17409468]