VINCRISTINE SULFATE
Clinical safety rating: avoid
Strong CYP3A4 inhibitors may increase levels Can cause severe peripheral neuropathy and extravasation injury.
Vincristine is a vinca alkaloid that binds to tubulin, inhibiting microtubule assembly and causing metaphase arrest in dividing cells. It disrupts mitotic spindle formation, leading to cell cycle arrest at M-phase and apoptosis in rapidly proliferating cells.
| Metabolism | Hepatic metabolism primarily via CYP3A4. Also metabolized by CYP3A5. Biliary excretion is the main route of elimination. |
| Excretion | Primarily biliary/fecal: ~70-80% excreted unchanged in bile and feces; renal: ~10-20% as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life: 19-35 hours (mean ~24 hours) in adults; prolonged to up to 85 hours in hepatic impairment or elderly. |
| Protein binding | Approximately 75-90% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 4-8 L/kg (mean ~6.5 L/kg), indicating extensive tissue binding and distribution. |
| Bioavailability | Oral: <5% (low due to P-glycoprotein efflux and first-pass metabolism); IV: 100%. |
| Onset of Action | IV: Clinical effect on microtubules within minutes to hours; maximal hematologic toxicity typically at 7-10 days. |
| Duration of Action | Duration of effect: Neurotoxicity may persist for weeks to months; bone marrow suppression resolves over 1-3 weeks; pharmacokinetic effects persist for >24 hours. |
| Molecular Weight | 923.04 |
1.4 mg/m2 IV push once weekly, maximum single dose 2 mg.
| Dosage form | Injectable |
| Renal impairment | No dose adjustment required for GFR >10 mL/min; consider alternative therapy if GFR <10 mL/min. |
| 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 single dose 2 mg; often dosed at 0.05 mg/kg for infants <10 kg. |
| Geriatric use | Monitor for neurotoxicity; consider starting at lower end of dosing range (e.g., 1 mg/m2). |
| 1st trimester | Contraindicated due to teratogenicity; embryotoxic and fetotoxic effects observed in animal studies. Case reports of fetal malformations and spontaneous abortion. Use only if benefit outweighs risk and no alternative. |
| 2nd trimester | Contraindicated; continues to carry teratogenic risk. May cause fetal growth restriction, oligohydramnios, and preterm birth. Consider discontinuation or alternative therapy if pregnancy desired. |
| 3rd trimester | Contraindicated; risk of neonatal toxicity including myelosuppression, neuropathy, and sepsis. Avoid use near term due to potential neonatal adverse effects. |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause severe peripheral neuropathy and extravasation injury.
| FDA category | Contraindicated |
| Placental transfer | Vincristine crosses the placenta. In vitro studies using human placenta show transfer; clinical evidence from case reports indicates fetal exposure correlates with maternal dose. Distribution to fetal tissues is documented. |
■ FDA Black Box Warning
Vincristine is for intravenous use only. Fatal if given intrathecally. Extreme care must be taken to avoid accidental intrathecal administration.
| Common Effects | lymphomas |
| Serious Effects |
Hypersensitivity to vincristine or any component of the formulationPatients with demyelinating conditions (e.g., Charcot-Marie-Tooth syndrome) due to risk of severe neuropathyIntrathecal administration (fatal)Severe hepatic impairment (bilirubin >3 mg/dL) due to reduced clearance and increased toxicityActive, severe infection (including varicella-zoster, herpes zoster) due to immunosuppression
| Precautions | Neurotoxicity (peripheral neuropathy, autonomic neuropathy, cranial nerve palsies), constipation and ileus, myelosuppression, extravasation risk, Stevens-Johnson syndrome, pulmonary toxicity, hepatotoxicity, tumor lysis syndrome, and risk of aspiration in elderly. |
| Food/Dietary |
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| Breastfeeding | Vincristine is excreted into human milk in low concentrations. However, due to potential for serious adverse reactions in the nursing infant (e.g., immunosuppression, neurotoxicity), breastfeeding is not recommended during therapy and for at least 2 weeks after the last dose (or longer based on drug half-life and infant risk). Consider alternative feeding methods. |
| Lactation Rating | L5 |
| Teratogenic Risk | Vincristine sulfate is teratogenic. First trimester exposure is associated with major congenital malformations including skeletal, cardiac, and CNS defects. Second and third trimester exposure risks include intrauterine growth restriction, fetal death, and neonatal myelosuppression. Contraindicated in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests, serum uric acid, and neurologic assessments. Fetal monitoring includes serial ultrasound for growth and amniotic fluid index, and nonstress test or biophysical profile during third trimester. |
| Fertility Effects | Vincristine can cause gonadal suppression, amenorrhea, and azoospermia. May lead to irreversible infertility in both sexes. Pre-treatment fertility preservation counseling recommended. |
| Grapefruit and grapefruit juice may inhibit CYP3A4-mediated metabolism of vincristine, potentially increasing toxicity; avoid concurrent use. No other significant food interactions reported. |
| Clinical Pearls | Vincristine is a vesicant; administer via running IV to avoid extravasation, which causes severe tissue necrosis. Dose-limiting toxicity is peripheral neuropathy, often starting with paresthesias in fingers and toes. Cumulative doses exceeding 15-20 mg increase neuropathy risk. Obtain CBC before each dose; watch for myelosuppression (especially neutropenia). Use with caution in hepatic impairment; dose reduction may be needed for bilirubin >3 mg/dL. Intrathecal administration is fatal; never use vincristine IT. |
| Patient Advice | Avoid contact of the drug with skin or eyes; report any burning or pain during infusion immediately. · Notify your doctor if you experience numbness, tingling, pain, or weakness in hands/feet; difficulty walking; or constipation (neuropathy). · Vincristine may cause constipation; increase fluid intake and fiber; use stool softeners if needed. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception during treatment and for at least 3 months after the last dose. · Do not receive live vaccines (e.g., MMR, varicella) while on vincristine. |