ONCOVIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ONCOVIN (ONCOVIN).
Vincristine is a vinca alkaloid that binds to tubulin, inhibiting microtubule formation and disrupting mitotic spindle assembly, leading to metaphase arrest and cell death.
| Metabolism | Vincristine is primarily metabolized by the hepatic cytochrome P450 system, specifically CYP3A4 and CYP3A5, to active and inactive metabolites. It is extensively distributed and excreted primarily via bile and feces. |
| Excretion | Primarily hepatobiliary (fecal) excretion: ~80% as unchanged drug and metabolites via bile into feces. Renal excretion: <10% unchanged in urine. Extensive metabolism in liver via CYP3A4. |
| Half-life | Terminal elimination half-life: approximately 19-155 hours (mean ~85 hours) in adults. In elderly and hepatic impairment, half-life is prolonged. Highly variable due to extensive tissue binding and prolonged terminal phase. |
| Protein binding | ~75% bound to serum proteins, primarily albumin and also to α1-acid glycoprotein and lipoproteins. |
| Volume of Distribution | Very large, mean Vd: 8.0-15.0 L/kg (range 6-20 L/kg) indicating extensive tissue binding and distribution into tissues including heart, liver, kidney, and peripheral nerves (highest in thyroid, liver, kidney, and lung). |
| Bioavailability | Oral bioavailability is negligible (<5%) due to extensive first-pass metabolism and active efflux by P-glycoprotein; therefore, not administered orally. Only approved via IV route. |
| Onset of Action | IV administration: Onset of clinical effect (e.g., mitotic arrest, symptomatic improvement) typically within 24-48 hours for solid tumors and leukemia. |
| Duration of Action | Duration of antimitotic effect persists for several days to weeks after a single dose. Neurotoxic effects (e.g., peripheral neuropathy) can be prolonged or irreversible. |
| Molecular Weight | 824.96 |
1.4 mg/m2 IV weekly, maximum single dose 2 mg
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR ≥ 10 mL/min; avoid in GFR < 10 mL/min not on dialysis |
| Liver impairment | Child-Pugh A: 1.4 mg/m2; Child-Pugh B: 50% dose reduction; Child-Pugh C: avoid |
| Pediatric use | 1.5-2 mg/m2 IV weekly, maximum 2 mg; BSA < 0.5 m2: 0.05 mg/kg weekly |
| Geriatric use | Monitor neurotoxicity; consider starting at 1 mg IV weekly |
| 1st trimester | Contraindicated; risk of fetal harm (teratogenic, embryotoxic). |
| 2nd trimester | Contraindicated; avoid due to continued fetal development risks. |
| 3rd trimester | Contraindicated; avoid near term due to risk of neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for ONCOVIN (ONCOVIN).
| Placental transfer | Crosses placenta; documented in animal and human studies. |
| Breastfeeding | Excreted into breast milk in low concentrations; due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy. |
| Lactation Rating |
■ FDA Black Box Warning
ONCOVIN (vincristine) is for intravenous use only. Intrathecal administration is fatal and can cause progressive paralysis, coma, and death. Syringes containing this product must be labeled 'For Intravenous Use Only' and should be prepared and dispensed in a manner that prevents intrathecal administration.
| Common Effects | Urinary tract infection |
| Serious Effects |
Hypersensitivity to vincristine or other vinca alkaloidsIntrathecal administration (fatal)Severe bone marrow suppressionActive infectionPregnancy
| Precautions | Neurotoxicity: Dose-limiting peripheral neuropathy, including motor, sensory, and autonomic dysfunction; risk increases with cumulative dose., Extravasation: Causes severe tissue damage if extravasation occurs; administer via running IV infusion with close monitoring., Neuromuscular toxicity: May cause severe constipation, paralytic ileus, or urinary retention; use prophylactic bowel regimen., Myelosuppression: May cause leukopenia, thrombocytopenia, and anemia; monitor blood counts regularly., Patients with pre-existing neuromuscular disease or prior neurotoxic chemotherapy are at higher risk for neurotoxicity., Hepatic impairment: Dose reduction recommended for significant hepatic dysfunction., Carcinogenicity: Has been associated with secondary malignancies., Fertility impairment: May cause irreversible testicular or ovarian failure. |
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| L5 (Contraindicated) |
| Teratogenic Risk | Pregnancy Category D. First trimester: high risk of fetal malformations including craniofacial defects, skeletal anomalies, and CNS abnormalities. Second and third trimesters: risk of intrauterine growth restriction, prematurity, myelosuppression, and neonatal pancytopenia. Avoid use in pregnant women unless potential benefit outweighs severe fetal risk. |
| Fetal Monitoring | Monitor complete blood count, liver function tests, and renal function weekly. Assess for neurotoxicity (peripheral neuropathy, constipation). Fetal monitoring: serial ultrasound for growth restriction and anomalies; fetal echocardiography for cardiotoxicity. Monitor neonatal hematologic status at birth. |
| Fertility Effects | Causes gonadal suppression in males (azoospermia) and females (ovarian failure, amenorrhea). May lead to permanent infertility. Alkylating-like effects on germinal epithelium. |
| Food/Dietary | Grapefruit and grapefruit juice may increase vincristine toxicity by inhibiting CYP3A4 metabolism. Avoid concurrent consumption. No other significant food interactions. |
| Clinical Pearls | ONCOVIN (vincristine) is a vinca alkaloid that inhibits microtubule formation, causing metaphase arrest. It is a vesicant; administer via IV push over 1 minute through a free-flowing IV line, avoiding extravasation. Neurotoxicity (peripheral neuropathy, constipation, jaw pain) is dose-limiting and cumulative. Dose reductions may be needed for hepatic impairment (bilirubin >3 mg/dL: reduce by 50%). Monitor for SIADH, especially with high doses. Avoid intrathecal administration (fatal). |
| Patient Advice | Report any numbness, tingling, or weakness in your hands or feet immediately. · Constipation is common; take stool softeners or laxatives as prescribed. · Avoid alcohol and grapefruit juice during treatment. · Do not receive live vaccines during therapy. · Notify your doctor if you experience jaw pain, hoarseness, or difficulty walking. · This drug can cause hair loss, which is usually reversible. |