Vincristine – Uses, Dosage, Side Effects, Interaction

Vincristine Sulfate Liposome is a sphingomyelin/cholesterol liposomal formulation of vincristine sulfate with potential antineoplastic activity. Vincristine, a vinca alkaloid isolated from the plant Vinca rosea, irreversibly binds to and stabilizes tubulin, thereby interrupting microtubule assembly/disassembly dynamics, thereby preventing the formation of the mitotic spindle and leading to cell cycle arrest in metaphase. Liposomal encapsulation prolongs the bioavailability of vincristine, increases its delivery to tumor tissues, and reduces its toxicity profile. Compared to standard liposomal delivery, schistosomal drug delivery further increases the circulation time of serum drug and enhances drug accumulation at tumor sites, thereby leading to a further increase in efficacy.

Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin’s disease, Kaposi’s sarcoma?, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multi ringed units, vindoline, and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumor properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effects. The vinca alkaloids are considered to be cell cycle phase-specific.

Use in Cancer

Etoposide phosphate is approved to be used with other drugs to treat:

• Small cell lung cancer. It is used with cisplatin as first-line therapy.
• Testicular cancer. It is used in patients who have already been treated with surgery, radiation therapy?, or other chemotherapy and have not gotten better.

Etoposide phosphate is also available in a different form called etoposide. For more information, see the Drug Information Summary for Etoposide.

Etoposide phosphate is also being studied in the treatment of other types of cancer.

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, cross-sensitivity cannot be ruled out due to the similarities in chemical structures and pharmacological actions.[rx]

• anemia?
• decreased blood platelets
• low levels of a type of white blood cell called neutrophils
• Charcot-Marie-Tooth disease
• generalized? disorder of peripheral nerves
• a painful condition that affects the nerves in the legs and arms called peripheral neuropathy?
• a disorder of the peripheral nerves that enable movement called peripheral motor neuropathy?
• a disease affecting muscles and nerves
• abnormal liver? function tests
• pregnancy
• a patient who is producing milk and breastfeeding

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

Extravasation: An 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. Therefore, 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. Therefore, 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.”

Dosage?

Strengths: 1 mg/mL

Malignant? Disease

• Manufacturer suggested dose: 1.4 mg/m2 IV over one minute once a week
• This dose is the manufacturer’s recommendation. It is only a guideline. The institutional protocol should be consulted.
• The dose of this drug may depend upon the specific indication? for its use, and whether other cytotoxic agents are coadministered. Subsequent doses may be determined by the clinical? and hematologic response of the patient. Solid Tumors
• Manufacturer suggested dose: 1.4 mg/m2 IV over one minute once a week

Pediatric Dose for Malignant Disease

Less than 18 years and less than or equal to 10 kg:

• Initial dose: 0.05 mg/kg IV over one minute once a week
• Maximum dose: 2 mg/m2 IV over one minute once a week
• Less than 18 years and greater than 10 kg: 1 to 2 mg/m2 IV over one minute once a week
• This dose is the manufacturer’s recommendation. It is only a guideline. The institutional protocol should be consulted.
• The dose of this drug may depend upon the specific indication for its use, and whether other cytotoxic agents are coadministered. Subsequent doses may be determined by the clinical and hematologic response of the patient.

Pediatric Dose for Solid Tumors

Less than 18 years and less than or equal to 10 kg:

• Initial dose: 0.05 mg/kg IV over one minute once a week
• Maximum dose: 2 mg/m2 IV over one minute once a week
• Less than 18 years and greater than 10 kg: 1 to 2 mg/m2 IV over one minute once a week

Side Effects

The Most Common

• nausea?
• vomiting?
• sores in the mouth and throat?
• loss of appetite or weight
• stomach pain
• diarrhea
• headache
• hair loss

More common

• hives
• rash
• itching
• difficulty breathing or swallowing
• constipation
• increased or decreased urination
• swelling of the face, arms, hands, feet, ankles, or lower legs
• unusual bleeding or bruising
• unusual tiredness or weakness
• pain, numbness, burning, or tingling in the hands or feet
• difficulty walking or unsteady walking
• muscle or joint pain
• sudden changes in vision, including loss of vision
• hearing loss
• dizziness
• loss of the ability to move muscles and to feel a part of the body
• hoarseness or loss of ability to speak loudly
• seizures
• jaw pain
• fever, sore throat, chills, or other signs of infection

Rare

• blurred or double vision
• confusion
• constipation
• decrease or increase in urination
• depression
• dizziness or lightheadedness when getting up from a sitting or lying position
• drooping eyelids
• hallucinations
• headache
• hearing loss
• jaw pain
• joint pain
• lack of perspiration
• loss of appetite
• lower back or side pain
• numbness or tingling in fingers and toes
• pain in fingers and toes
• pain in testicles
• painful or difficult urination
• sleeping problems
• sores in mouth and on lips
• stomach cramps
• swelling of feet or lower legs
• weakness
• unconsciousness

Drug Interaction

Pregnancy and Lactation

FDA Pregnancy category D

Pregnancy

There is a possibility of birth defect if either partner is using vincristine at the time of conception, or if it is taken during pregnancy. It may also harm the baby in other ways if used during pregnancy. Use effective birth control while you are taking this medication, and tell the doctor immediately if you become pregnant.

Breast-feeding

It is not known whether vincristine passes into breast milk. Because of the risk of harm to the infant, women should not breastfeed while receiving vincristine.

References