vincristine sulfate
Oncovin, Vincasar PFS

Available forms
Available by prescription only
Injection: 1 mg/1 ml, 2 mg/2 ml, 5 mg/5 ml in multiple-dose vials; 1 mg/1 ml, 2 mg/2 ml, 5 mg/ml in preservative-free vials

Indications and dosages
Dosage and indications may vary. Check current literature for recommended protocol.
 Acute lymphoblastic and other leukemias; Hodgkin’s disease; lymphosarcoma; reticulum cell, osteogenic, and other sarcomas; neuroblastoma; rhabdomyosarcoma; Wilms’ tumor; lung cancer; breast cancer ◇. Adults: 1.4 mg/m² I.V. weekly. Maximum single dose (adults and children) is 2 mg.
Children: 2 mg/m² I.V. weekly.
Children who weigh less than 10 kg (22 lb) or have a body surface area less than 1 m²: 0.05 mg/kg once weekly.
≡ Dosage adjustment. Reduce dosage by 50% in patients with direct serum bilirubin level exceeding 3 ml/dl or other evidence of significant hepatic impairment.

Pharmacodynamics
Antineoplastic action: Exerts cytotoxic activity by arresting the cell cycle in the metaphase portion of cell division, resulting in a blockade of mitosis. Also inhibits DNA-dependent RNA synthesis and interferes with amino acid metabolites, inhibiting purine synthesis.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Rapidly and widely distributed into body tissues; bound to erythrocytes and platelets. Drug crosses blood-brain barrier but doesn’t achieve therapeutic levels in CSF.
Metabolism: Extensively metabolized in liver.
Excretion: Drug and metabolites primarily excreted into bile. Smaller portion eliminated through kidneys. Triphasic plasma elimination; half-lives of about 4 minutes, 2 1/4 hours, and 85 hours for distribution, second, and terminal phases, respectively.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those who have the demyelinating form of Charcot-Marie-Tooth syndrome. Don’t give to patients who are receiving radiation therapy through ports that include the liver. Use cautiously in patients with hepatic dysfunction, neuromuscular disease, or infection.

Interactions
Drug-drug. Asparaginase: Decreases hepatic clearance of vincristine. Adjust vincristine dosage.
Calcium channel blockers: Enhances vincristine accumulation in cells. Monitor patient closely; adjust vincristine dosage.
Digoxin: Decreases digoxin levels. Monitor serum digoxin levels.
Methotrexate: Increases therapeutic effect of methotrexate. May require a lower dosage of methotrexate.
Mitomycin: May increase frequency of bronchospasm and acute pulmonary reactions. Avoid use together.
Neurotoxic drugs: Increases neurotoxicity; causes additive effect. Monitor patient closely; adjust vincristine dosage as needed.
Phenytoin: May decrease plasma phenytoin levels. Monitor phenytoin levels.

Adverse reactions
CNS: fever, peripheral neuropathy, sensory loss, loss of deep tendon reflexes, paresthesia, wristdrop and footdrop, seizures, coma, headache, ataxia, cranial nerve palsies, jaw pain, hoarseness, vocal cord paralysis, muscle weakness and cramps.
CV: hypotension, hypertension.
EENT: diplopia, optic and extraocular neuropathy, ptosis, photophobia, transient cortical blindness, optical atrophy.
GI: diarrhea, constipation, cramps, ileus that mimics surgical abdomen, paralytic ileus, nausea, vomiting, anorexia, dysphagia, intestinal necrosis, stomatitis.
GU: urine retention, dysuria, acute uric acid neuropathy, polyuria.
Hematologic: anemia, leukopenia, thrombocytopenia.
Metabolic: hyperuricemia, hyponatremia, weight loss.
Respiratory: acute bronchospasm, dyspnea.
Skin: reversible alopecia; severe local reaction with extravasation; phlebitis, cellulitis at injection site.
Other: SIADH.

Effects on lab test results
• May decrease sodium levels.
• May decrease hemoglobin and WBC and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include alopecia, myelosuppression, paresthesia, neuritic pain, motor difficulties, loss of deep tendon reflexes, nausea, vomiting, and ileus.
 Treatment is usually supportive and includes transfusion of blood components, antiemetics, enemas for ileus, phenobarbital for seizures, and other appropriate symptomatic therapy. Administration of calcium leucovorin at a dosage of 15 mg I.V. every 3 hours for 24 hours, and then every 6 hours for 48 hours may help protect cells from the toxic effects of vincristine.

Special considerations
• Drug may be administered by I.V. push injection over 1 minute into the tubing of a freely flowing I.V. infusion.
• Dilution into larger volumes isn’t recommended for infusion into peripheral veins; this method increases risk of extravasation. Drug may be administered as an I.V. infusion through a central venous catheter.
 ALERT Extravasation may cause necrosis. Manufacturer recommends treatment with moderate heat to the area and prompt administration of intradermal hyaluronidase. See package insert for additional recommendations.
• Because of potential for neurotoxicity, don’t give drug more than once weekly. Children are more resistant to neurotoxicity than adults. Neurotoxicity is dose-related and usually reversible; reduce dosage if symptoms of neurotoxicity develop. Some neurotoxicities may be permanent.
• Prevent uric acid nephropathy with generous oral fluid intake and administration of allopurinol. Alkalinization of urine may be required if serum uric acid level is increased.
• Reduced dosage may be needed in patients with obstructive jaundice or liver disease.
 ALERT Don’t confuse vincristine with vinblastine or vindesine.
• Drug may cause SIADH. Treatment requires fluid restriction and a loop diuretic.
 ALERT Management of patients mistakenly receiving intrathecal vincristine is a medical emergency. Prognosis is generally poor.
 ALERT After administering drug, monitor patient for life-threatening bronchospasm. It’s most likely to occur in patients also receiving mitomycin.
• Watch for neurotoxicity by checking for depression of Achilles tendon reflex, numbness, tingling, footdrop or wristdrop, difficulty in walking, ataxia, and slapping gait. Also check ability to walk on heels.
• Monitor patient’s bowel function. Patient should have stool softener, laxative, or water before dosing. Constipation may be an early indication of neurotoxicity.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. However, because of risk of serious adverse reactions, mutagenicity, and carcinogenicity in infant, breast-feeding isn’t recommended.
Geriatric patients
• Elderly patients who are weak or bedridden may be more susceptible to neurotoxic effects. Use cautiously.

Patient education
• Encourage adequate fluid intake to increase urine output and facilitate excretion of uric acid.
• Tell patient to call regarding use of laxatives if constipation or stomach pain occurs.
• Assure patient that hair should grow back after therapy ends.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use