Vincristine Sulfate

Pronunciation: (vin-KRISS-teen)
Class: Vinca alkaloid

Trade Names

Oncovin
- Solution for Injection 1 mg/mL

Pharmacology

Mode of action is unknown. In vitro, vincristine arrests mitotic division at metaphase. It reversibly binds to microtubule and spindle proteins in the S phase.

Pharmacokinetics

Absorption

Very rapidly absorbed via IV (15 to 30 min).

Distribution

More than 90% of drug is distributed from blood to tissue, where it remains tightly but not irreversibly. Penetration across the blood brain barrier is poor.

Metabolism

Triphasic serum decay following rapid IV injection.

Elimination

Terminal t _½ is 85 h (19 to 155 h). Liver is the major excretory organ. 80% of the dose appears in the feces, 10% to 20% in the urine.

Onset

15 to 30 min.

Special Populations

Hepatic Function Impairment

A 50% reduction in dose is recommended for patients having a direct serum bilirubin more than 3 mg/dL.

Indications and Usage

Adult/Pediatric

Acute lymphocytic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, Wilms tumor.

Unlabeled Uses

Small-cell lung carcinoma, brain tumors, multiple myeloma, Kaposi sarcoma, chronic lymphocytic and myelocytic leukemias, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura.

Contraindications

Patients with demyelinating form of Charcot-Marie-Tooth syndrome.

Dosage and Administration

Acute Lymphocytic Leukemia, Lymphomas, Rhabdomyosarcoma, Neuroblastoma, Wilms Tumor
Adult

IV 1.4 mg/m ² weekly (typical dose, 2 mg).

Children weighing more than 10 kg (or body surface area at least 1 m ² )

IV 1.4 to 2 mg/m ² weekly for 3 to 8 wk. Do not exceed a max of 2 mg/dose.

Children weighing up to 10 kg (or body surface area less than 1 m ² )

IV 0.05 mg/kg weekly initially. Titrate dose as tolerated, up to a max of 2 mg/dose. Continue therapy for 3 to 8 wk.

Adjustment in Hepatic Insufficiency
Adult

IV A 50% reduction in dose is recommended for patients having a direct serum bilirubin value more than 3 mg/dL.

Neuroblastoma, Combination Therapy
Children weighing more than 10 kg (or body surface area at least 1 m ² )

IV Vincristine 1 mg/m ² /day by continuous infusion over 24 h for 3 days (total dose of 3 mg/m ² over a 3-day period).

General Advice

Do not dilute vincristine for routine IV use. For continuous IV infusion, vincristine may be diluted with 0.9% Sodium Chloride or 5% Dextrose.
Administer by IV injection or continuous IV infusion.
Do not filter.
Give over a 1-min period by IV push injection or IV side arm into a running infusion.
Continuous infusions can only be administered through a central venous catheter resting in the vena cava. A peripherally-inserted central catheter, or PICC line, may also be appropriate.

Storage/Stability

Refrigerate. Protect from light.

Drug Interactions

CYP-450 inhibitors

Vincristine elimination may be reduced by CYP-450 enzyme inhibitors.

Digoxin

May decrease digoxin plasma concentration.

Itraconazole

Vincristine neurotoxicity has occurred during coadministration.

L-asparaginase

Vincristine clearance may decrease when L-asparaginase is given prior to vincristine. Give vincristine 12 to 24 hr prior to L-asparaginase.

Mitomycin

Acute shortness of breath and severe bronchospasm have occurred following concomitant or previous use of mitomycin.

Phenytoin

May reduce phenytoin plasma concentration.

Quinolone antibiotics

Vincristine may decrease oral absorption of quinolone antibiotics.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension; hypotension; MI.

CNS

Autonomic and peripheral neuropathy; headache.

Dermatologic

Alopecia; rash

GI

Mucositis; abdominal cramps; diarrhea; anorexia; intestinal necrosis or perforation; constipation that can lead to upper colon impaction; paralytic ileus; weight loss.

Genitourinary

Amenorrhea; polyuria; dysuria; urinary retention because of bladder atony; azoospermia.

Hematologic

Bone marrow suppression; nadir less than 7 days.

Musculoskeletal

Acute bone or jaw pain.

Respiratory

Acute shortness of breath; severe bronchospasm.

Special Senses

Optic atrophy with blindness; transient cortical blindness; ptosis; diplopia; photophobia.

Miscellaneous

Fever.

Precautions

Warnings

IV use only

Intrathecal use of other vinca alkaloids has been fatal. Label syringe “Warning - For IV Use Only; fatal if given intrathecally.”

Granulocytopenia

May be severe and predispose to infection. Do not administer to patients with granulocyte counts less than 1,000 cells/mm ³ .

Avoid extravasation

Proper placement of needle/catheter prior to administration. Local irritation or phlebitis may occur. Refer to your institution specific protocol.

Pregnancy

Category D . Can cause fetal harm when administered to pregnant women.

Lactation

Undetermined.

Hypersensitivity

Hypersensitivity temporally related to vincristine therapy has occurred.

Dosage adjustment (pediatric)

Follow dosage adjustment guidelines recommended for adults.

CNS leukemia

CNS leukemia has occurred. Additional agents may be required.

Pulmonary reactions

Acute shortness of breath and severe bronchospasm have occurred, most frequently when the drug was used with mitomycin-C.

Overdosage

Symptoms

Side effects are dose-related. Expect exaggerated side effects.

Patient Information

Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve max benefit possible.
Review dosing schedule with patient, family, or caregiver.
Advise patient, family, or caregiver that medication may cause hair loss but that it is reversible when therapy is stopped.
Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; shortness of breath or difficulty breathing; abnormal skin sensations; stumbling; muscle wasting; fever, chills, or other signs of infection; redness or swelling at injection site.
Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, constipation, diarrhea, or appetite loss; persistent or worsening general body weakness.
Caution women of childbearing potential to avoid becoming pregnant during therapy.