VINCREX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VINCREX (VINCREX).
Vinca alkaloid that binds to tubulin, inhibiting microtubule formation, thus disrupting mitotic spindle assembly and arresting cell division at metaphase.
| Metabolism | Primarily hepatic via CYP3A4; excreted in bile and feces. |
| Excretion | Primarily hepatic metabolism via CYP3A4, with biliary excretion of metabolites (65-75% in feces). Renal excretion accounts for 10-20% as unchanged drug and metabolites. Minimal (1-3%) in urine as parent compound. |
| Half-life | Terminal elimination half-life is 18-36 hours (mean 27 hours) in adults; prolonged in hepatic impairment (up to 60 hours) due to reduced clearance. |
| Protein binding | 85-90% bound primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.0 L/kg (mean 0.9 L/kg) indicating extensive tissue distribution; crosses blood-brain barrier with CNS concentrations ~20% of plasma. |
| Bioavailability | Oral: 35-45% (due to first-pass metabolism); Sublingual: 50-60%; Intramuscular: 80-90%. |
| Onset of Action | Intravenous: 5-10 minutes; Oral: 1-2 hours (time to peak concentration). Clinical effect correlates with plasma levels. |
| Duration of Action | Intravenous: 4-6 hours (clinical effect); Oral: 8-12 hours (sustained release). Duration may increase with renal/hepatic impairment. |
| Molecular Weight | 810.98 Da |
1.5 mg/m2 IV push weekly, maximum single dose 2 mg.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >= 50 mL/min: no adjustment; CrCl 30-49 mL/min: reduce dose by 25%; CrCl < 30 mL/min: reduce dose by 50%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 2 mg/m2 IV weekly, with dose capped at 2 mg for body surface area >1.33 m2; for infants <6 months: 1.5 mg/m2. |
| Geriatric use | Use with caution; consider starting at 1.2 mg/m2 due to increased susceptibility to neurotoxicity; monitor closely for peripheral neuropathy. |
| 1st trimester | Contraindicated due to teratogenic effects. Vinca alkaloids cause fetal malformations in animal studies. |
| 2nd trimester | Contraindicated. Risk of fetal harm outweighs any potential benefit. |
| 3rd trimester | Contraindicated. May cause fetal bradycardia, hematologic toxicity, or neurotoxicity. |
Clinical note
Comprehensive clinical and safety monograph for VINCREX (VINCREX).
| Placental transfer | Crosses the human placenta. Vinca alkaloids are known to concentrate in fetal tissues with evidence of embryotoxicity. |
| Breastfeeding | Excreted into breast milk in low concentrations. Due to potential for serious adverse reactions (e.g., immunosuppression, neutropenia) in the nursing infant, breastfeeding is not recommended during therapy and for at least 30 days after last dose. |
■ FDA Black Box Warning
For intravenous use only. Intrathecal administration is fatal.
| Serious Effects |
Hypersensitivity to vinorelbine or other vinca alkaloidsSevere pre-existing neutropenia (absolute neutrophil count < 1000 cells/mm³)Current or recent severe infectionConcurrent yellow fever vaccine
| Precautions | Extravasation (severe tissue damage), neurotoxicity (peripheral neuropathy, constipation, seizures), myelosuppression (neutropenia, thrombocytopenia), pulmonary toxicity (bronchospasm, dyspnea), and tumor lysis syndrome. |
| Food/Dietary | Grapefruit and grapefruit juice may inhibit CYP3A4 metabolism, potentially increasing vincristine toxicity. Avoid concurrent consumption. No other significant food interactions. |
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| Lactation Rating |
| L5 (Avoid) |
| Teratogenic Risk | Vincristine is contraindicated in pregnancy. First trimester: High risk of major congenital malformations, spontaneous abortion, and embryotoxicity. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and neonatal pancytopenia. Avoid use unless life-threatening maternal condition. |
| Fetal Monitoring | Maternal: Complete blood count with differential, liver function tests, renal function, serum electrolytes, neurologic examination for peripheral neuropathy, and cardiac monitoring per protocol. Fetal: Serial ultrasound for growth, amniotic fluid volume, and biophysical profile; consider fetal echocardiogram if second/third trimester exposure. |
| Fertility Effects | May cause ovarian failure, amenorrhea, azoospermia, and infertility; effects can be irreversible. Sperm and oocyte cryopreservation recommended prior to treatment. |
| Clinical Pearls | Vincristine (VINCREX) is a vinca alkaloid that inhibits microtubule formation, causing metaphase arrest. It is highly neurotoxic, with dose-limiting peripheral neuropathy manifesting as loss of deep tendon reflexes, paresthesias, and motor weakness. Extravasation causes severe tissue necrosis; administer via central line if possible. Oral bioavailability is poor; give IV push over 1 minute. Dose reduction needed for hepatic impairment (bilirubin >3 mg/dL). |
| Patient Advice | Report any numbness, tingling, or weakness in hands/feet immediately. · Avoid constipation by increasing fluid intake and using stool softeners; report if no bowel movement for 3 days. · Do not receive live vaccines during treatment. · Use effective contraception during and for 6 months after therapy. · This drug is a vesicant; report any burning or redness at IV site immediately. |