VINCASAR PFS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VINCASAR PFS (VINCASAR PFS).
Vincristine is a vinca alkaloid that binds to tubulin, inhibiting microtubule formation and disrupting mitotic spindle assembly, thereby arresting cell division in metaphase.
| Metabolism | Primarily hepatic metabolism via CYP3A4, with biliary excretion; minor renal elimination. |
| Excretion | Primarily hepatobiliary excretion; approximately 80% of the dose is eliminated in feces, with less than 20% excreted unchanged in urine. Renal clearance is minor. |
| Half-life | Terminal elimination half-life ranges from 24 to 35 hours in adults, with a mean of approximately 25 hours. The half-life may be prolonged in patients with hepatic impairment. |
| Protein binding | About 75% bound to plasma proteins, primarily albumin and beta-globulins. |
| Volume of Distribution | Volume of distribution is large, approximately 8 L/kg (range 4–15 L/kg), indicating extensive tissue binding and distribution into peripheral compartments. |
| Bioavailability | Not administered orally; intravenous administration yields 100% bioavailability. |
| Onset of Action | Following IV administration, clinical effects (e.g., reduction in white blood cell count in leukemia) are typically observed within 7 to 10 days, with maximum effect around 10–14 days. |
| Duration of Action | Duration of myelosuppressive effect is typically 1 to 3 weeks, but can vary depending on the specific chemotherapeutic regimen and patient factors. Neurotoxicity may persist for weeks to months after discontinuation. |
| Molecular Weight | 923.04 |
1.4 mg/m2 intravenously once weekly, typically not exceeding 2 mg.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment necessary for GFR ≥10 mL/min; for GFR <10 mL/min, reduce dose by 50%. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use or reduce dose by 75%. |
| Pediatric use | 1.5-2 mg/m2 intravenously once weekly, with maximum single dose of 2 mg. |
| Geriatric use | Consider starting at 1 mg/m2 intravenously once weekly due to increased risk of neurotoxicity; monitor closely. |
| 1st trimester | Contraindicated due to teratogenicity (embryotoxic, fetotoxic). Can cause fetal malformations, spontaneous abortion. Use only if benefit outweighs risk, but generally avoid. |
| 2nd trimester | Teratogenic risk persists; avoid use unless essential. May cause fetal growth restriction and other adverse outcomes. |
| 3rd trimester | Avoid near term due to risk of neonatal toxicity (e.g., myelosuppression, infection). Contraindicated in pregnancy unless necessary for maternal survival. |
Clinical note
Comprehensive clinical and safety monograph for VINCASAR PFS (VINCASAR PFS).
| Placental transfer | Vincristine crosses the placenta; animal studies show embryotoxicity and teratogenicity. Human data limited but suggest transfer and potential harm. |
| Breastfeeding | Excreted into breast milk in low concentrations. Due to potential for serious adverse effects in nursing infants (e.g., immunosuppression, neutropenia), breastfeeding is not recommended during therapy. Consider withholding breastfeeding for at least one week after last dose. |
■ FDA Black Box Warning
Vincristine is for intravenous use only. Fatal if given intrathecally. Extravasation can cause severe local tissue injury.
| Serious Effects |
Hypersensitivity to vincristine or any componentPatients with the demyelinating form of Charcot-Marie-Tooth syndromeIntrathecal administration (fatal)Severe hepatic impairment (modify dose, but contraindicated if severe)Active infection (relative, but caution)
| Precautions | Neurotoxicity (peripheral neuropathy, autonomic neuropathy, cranial nerve palsies), constipation/ileus, myelosuppression, extravasation, hepatic impairment, pulmonary toxicity, SIADH, ocular toxicity. |
| Food/Dietary | Grapefruit and grapefruit juice may increase vincristine exposure and risk of toxicity. Avoid consumption of grapefruit and grapefruit juice during treatment. No other significant food interactions are established. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Vincasar PFS is embryotoxic and teratogenic. First trimester exposure carries high risk of spontaneous abortion and major congenital malformations, including skeletal, CNS, and cardiac defects. Second and third trimester exposure is associated with fetal growth restriction, oligohydramnios, and potential neurodevelopmental impairment. Contraindicated in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests (LFTs), renal function, and serum uric acid. Assess for neurotoxicity (peripheral neuropathy, constipation, ileus). Fetal monitoring includes serial ultrasounds for growth, amniotic fluid volume, and anatomy; consider fetal echocardiography. Monitor maternal ECG and electrolytes. |
| Fertility Effects | Potential for ovarian failure and azoospermia; may cause irreversible infertility. Pre-treatment fertility preservation counseling recommended. |
| Clinical Pearls | Vincristine (VINCASAR PFS) is a vinca alkaloid that causes peripheral neuropathy by binding to tubulin and disrupting microtubule formation. It is a vesicant; administer via IV push over 1 minute into a freely flowing IV line and avoid extravasation. Dose-limiting toxicity is neurotoxicity (e.g., loss of deep tendon reflexes, paresthesias), not myelosuppression. Monitor for constipation and paralytic ileus due to autonomic neuropathy. Use with caution in patients with hepatic impairment (reduce dose) or pre-existing neuropathy. Do not give intrathecally (fatal). |
| Patient Advice | Avoid grapefruit and grapefruit juice during treatment as they may increase side effects. · Report any numbness, tingling, or weakness in your hands or feet immediately. · Drink plenty of fluids and use stool softeners to prevent constipation. · This drug may cause hair loss, which is usually temporary. · Use effective contraception during treatment and for at least 6 months after the last dose. · Tell your doctor if you have any pain, redness, or swelling at the injection site. |