VINCRISTINE SULFATE PFS
Clinical safety rating: avoid
Contraindicated (not allowed)
Vincristine is a vinca alkaloid that binds to tubulin, inhibiting microtubule formation and disrupting mitotic spindle assembly, causing metaphase arrest in dividing cells.
| Metabolism | Primarily hepatic via CYP3A4; excreted in bile and feces; renal excretion is minor. |
| Excretion | Primarily hepatobiliary excretion (70-80%); renal excretion accounts for 10-20% (mostly metabolites); <1% excreted unchanged in urine. |
| Half-life | Terminal half-life is 19-155 hours (mean ~85 hours) in adults; prolonged in hepatic impairment or elderly. |
| Protein binding | 75-90% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 4-10 L/kg (large, indicating extensive tissue binding and distribution). |
| Bioavailability | Oral bioavailability is <10% (not administered orally); administered IV only. |
| Onset of Action | IV: Onset within 4-7 days for hematologic effects; peak effect at 7-10 days. |
| Duration of Action | Duration of action: Approximately 7-10 days; neurotoxicity may persist for weeks to months after cessation. |
| Molecular Weight | 923.04 Da |
1.4 mg/m2 IV push weekly, maximum single dose 2 mg.
| Dosage form | INJECTABLE |
| Renal impairment | No adjustment required for GFR >10 mL/min; for GFR ≤10 mL/min, consider 50% dose reduction. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 75%. |
| Pediatric use | 1.5-2 mg/m2 IV weekly, maximum 2 mg; for infants ≤10 kg: 0.05 mg/kg IV weekly. |
| Geriatric use | Start at lower end of dosing range (e.g., 1 mg/m2) due to increased risk of neurotoxicity; monitor closely. |
| 1st trimester | Contraindicated due to high risk of teratogenicity; embryotoxic in animal studies. |
| 2nd trimester | Contraindicated; may cause fetal harm. Use only if benefit outweighs risk. |
| 3rd trimester | Contraindicated; potential for neonatal adverse effects (e.g., myelosuppression). |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause severe peripheral neuropathy and extravasation injury.
| Placental transfer | Crosses placenta based on animal studies and human case reports. |
| Breastfeeding | Excreted into breast milk in small amounts; potential for serious adverse reactions in nursing infants. Discontinue breastfeeding during therapy. |
| Lactation Rating |
■ FDA Black Box Warning
For intravenous use only; fatal if given intrathecally. Must be administered under the supervision of a physician experienced in cancer chemotherapy.
| Common Effects | lymphomas |
| Serious Effects |
Hypersensitivity to vincristine or any component of the formulationIntrathecal administration (fatal)Severe hepatic impairmentActive severe infectionCharcot-Marie-Tooth disease (or other demyelinating conditions)
| Precautions | Neurotoxicity (peripheral neuropathy, areflexia, autonomic dysfunction); myelosuppression; constipation and ileus; extravasation risk; monitor hepatic function; dose adjustments in hepatic impairment. |
| Food/Dietary | Avoid grapefruit and grapefruit juice, as they inhibit CYP3A4 and may increase vincristine toxicity. No other significant food interactions are known. Maintain adequate hydration and fiber intake to prevent constipation. |
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| L5 (Contraindicated) |
| Teratogenic Risk | Vincristine is embryotoxic and fetotoxic in animals. First trimester exposure carries a high risk of spontaneous abortion and major congenital malformations (e.g., skeletal, cardiac, CNS). Second and third trimester use may cause fetal growth restriction, oligohydramnios, and neonatal myelosuppression. Use is contraindicated in pregnancy unless no alternative. |
| Fetal Monitoring | Maternal: Complete blood count with differential, liver function tests, serum uric acid, renal function, neurological exam for peripheral neuropathy. Fetal: Ultrasound for growth and amniotic fluid volume every 4-6 weeks if used in second/third trimester; consider fetal echocardiography if first-trimester exposure occurred. |
| Fertility Effects | Vincristine can cause ovarian failure and amenorrhea in females and oligospermia or azoospermia in males, potentially irreversible. Antral follicle count may decrease. Pre-treatment fertility preservation counseling is recommended for patients of reproductive potential. |
| Clinical Pearls | Vincristine sulfate is a vinca alkaloid that inhibits microtubule formation, causing metaphase arrest. It is a vesicant; administer intravenously via a secure line to avoid extravasation, which causes severe tissue necrosis. Monitor for peripheral neuropathy, which is dose-limiting and cumulative. Constipation is common; initiate prophylactic bowel regimen (e.g., stool softeners, laxatives). Avoid intrathecal administration, as it is fatal. Dose adjustments may be needed in hepatic impairment; no renal adjustment required. Check for drug interactions with CYP3A4 inhibitors/inducers, as they can alter vincristine metabolism. |
| Patient Advice | This medication is given intravenously by a healthcare professional; it must never be given into the spine. · You may experience numbness, tingling, or pain in your hands or feet; report these symptoms immediately. · Constipation is a common side effect; you should take stool softeners and laxatives as prescribed. · Avoid grapefruit and grapefruit juice during treatment as they may affect how the drug works. · Notify your healthcare provider if you develop fever, sore throat, easy bruising, or unusual bleeding. · This drug may cause hair loss; this is usually temporary and hair will grow back after treatment ends. · Women of childbearing age should use effective contraception during treatment and for at least 3 months after the last dose. |