VINCRISTINE SULFATE

Clinical safety rating: avoid

Strong CYP3A4 inhibitors may increase levels Can cause severe peripheral neuropathy and extravasation injury.

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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).

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inhibitors may increase levels Can cause severe peripheral neuropathy and extravasation injury.

FDA category	Contraindicated
Breastfeeding	Excretion into human milk is unknown; M/P ratio not available. Due to potential for severe adverse reactions in nursing infants, including myelosuppression and neurotoxicity, breastfeeding is contraindicated during therapy and for at least 1 month after last dose.
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.

Warnings & precautions

■ FDA Black Box Warning

Vincristine is for intravenous use only. Fatal if given intrathecally. Extreme care must be taken to avoid accidental intrathecal administration.

Side Effect Profile

Common Effects	lymphomas
Serious Effects

Absolute Contraindications

Hypersensitivity to vincristine or any component, patients with Charcot-Marie-Tooth disease, intrathecal administration (contraindicated), and concurrent use with live vaccines.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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VINCRISTINE SULFATE

Clinical safety rating: avoid

Strong CYP3A4 inhibitors may increase levels Can cause severe peripheral neuropathy and extravasation injury.

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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).

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inhibitors may increase levels Can cause severe peripheral neuropathy and extravasation injury.

FDA category	Contraindicated
Breastfeeding	Excretion into human milk is unknown; M/P ratio not available. Due to potential for severe adverse reactions in nursing infants, including myelosuppression and neurotoxicity, breastfeeding is contraindicated during therapy and for at least 1 month after last dose.
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.

Warnings & precautions

■ FDA Black Box Warning

Vincristine is for intravenous use only. Fatal if given intrathecally. Extreme care must be taken to avoid accidental intrathecal administration.

Side Effect Profile

Common Effects	lymphomas
Serious Effects

Absolute Contraindications

Hypersensitivity to vincristine or any component, patients with Charcot-Marie-Tooth disease, intrathecal administration (contraindicated), and concurrent use with live vaccines.