Criston

Approved Indications:

• Acute Lymphoblastic Leukemia (ALL)
  – Used during induction, consolidation, and maintenance therapy in pediatric and adult patients.
• Hodgkin's Lymphoma
  – Typically part of combination regimens such as MOPP or ABVD.
• Non-Hodgkin’s Lymphoma (NHL)
  – Effective in combination chemotherapy (e.g., CHOP protocol).
• Rhabdomyosarcoma
  – Included in pediatric soft tissue sarcoma protocols.
• Neuroblastoma
  – Used in early and advanced stages, often as part of multidrug chemotherapy.
• Wilms’ Tumor
  – Administered with dactinomycin and/or doxorubicin as per staging.
• Ewing’s Sarcoma and other Sarcomas
  – Component of combination regimens (e.g., VAC or VDC).

Important Off-label or Accepted Uses:

• Multiple Myeloma – as part of VAD regimen (Vincristine, Adriamycin, Dexamethasone).
• Brain tumors (e.g., medulloblastoma, gliomas) – as part of pediatric chemotherapy protocols.
• Immune Thrombocytopenia (ITP) – salvage therapy in chronic or refractory cases.

Route of Administration:
Intravenous only. Vincristine sulfate must never be administered intrathecally due to fatal neurotoxicity.

Adults:

• Usual dose: 1.4 mg/m² IV once weekly.
• Maximum single dose: 2 mg to avoid cumulative neurotoxicity.

Pediatrics:

• Dose range: 1.5–2 mg/m² IV weekly (max 2 mg/dose), adjusted per protocol.

Elderly:

• Use with caution. No specific adjustment unless comorbidities present; monitor closely for neurotoxicity.

Renal Impairment:

• No major dose adjustment required; however, caution is advised.

Hepatic Impairment:

• If bilirubin 1.5–3 mg/dL: reduce dose by 50%.
• If bilirubin >3 mg/dL: reduce dose by 75%.

Administration Notes:

• IV push or short IV infusion.
• Must be diluted appropriately.
• Administer through a secure vein; extravasation should be avoided.
• Use protective gloves; hazardous drug.

Vincristine binds to the β-tubulin subunit of microtubules, inhibiting their polymerization and disrupting the formation of the mitotic spindle. This arrests dividing cells in the metaphase of mitosis, leading to apoptosis. It is most active during the M-phase of the cell cycle. By disrupting microtubule dynamics, vincristine impairs intracellular transport mechanisms, contributing to neurotoxicity.

• Absorption: Not orally absorbed; given IV.
• Distribution: Widely distributed; high affinity for nervous tissue and bone marrow. Large volume of distribution (~3–8 L/kg).
• Protein Binding: ~75%.
• Metabolism: Primarily hepatic via CYP3A4. Metabolites less active.
• Half-life: Triphasic – Terminal half-life ~85 hours.
• Excretion: Mainly via biliary/fecal route; <10% renally excreted.
• Time to Peak Effect: Cell cycle-specific; depends on tumor type and combination.

• Pregnancy Category D (FDA):
  Evidence of fetal harm. Vincristine may cause teratogenicity, fetal loss, or intrauterine growth restriction. Use only if benefit justifies the risk.
• Lactation:
  Excretion into breast milk is unknown, but due to potential serious adverse effects (e.g., immunosuppression, cytopenia), breastfeeding is not recommended during treatment.

• Primary Class: Antineoplastic agent
• Subclass: Vinca alkaloid
• Mechanistic Class: Mitotic inhibitor (M-phase specific)

• Known hypersensitivity to vincristine or any component of the formulation
• Intrathecal administration (absolute contraindication)
• Patients with Charcot-Marie-Tooth syndrome (particularly the Dejerine–Sottas variant)
• Obstructive jaundice (dose-limiting)
• Severe leukopenia unless due to malignancy

• Black Box Warning: Fatal if administered intrathecally.
• Neurotoxicity: Dose-limiting peripheral neuropathy (paresthesia, foot drop, jaw pain, constipation, ileus). Monitor closely.
• Bone marrow suppression: Mild compared to other agents, but additive when combined.
• SIADH: Monitor electrolytes and fluid status.
• Tumor lysis syndrome: May occur in fast-growing tumors; hydrate and monitor uric acid.
• Fertility effects: May impair spermatogenesis and ovulation.
• Extravasation risk: Can cause tissue necrosis.

Common Adverse Effects:

• Neurologic: Peripheral neuropathy, jaw pain, foot drop, autonomic neuropathy (constipation, ileus, urinary retention)
• Gastrointestinal: Constipation, nausea, abdominal cramps
• Hematologic: Mild myelosuppression (leukopenia)
• General: Fatigue, alopecia, weight loss

Serious/Rare Side Effects:

• Paralytic ileus
• Seizures
• SIADH (hyponatremia)
• Respiratory distress
• Acute uric acid nephropathy
• Hepatotoxicity (rare)

Onset/Severity:

• Neuropathy is cumulative and dose-dependent. GI effects may occur within hours to days.

• CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin): May increase vincristine levels → enhanced neurotoxicity.
• CYP3A4 inducers (e.g., rifampin, phenytoin): May reduce efficacy.
• Azole antifungals: Avoid co-administration; increases risk of toxicity.
• Digoxin: May reduce serum levels of digoxin.
• Neurotoxic agents (e.g., isoniazid, platinum compounds): Additive neurotoxicity.
• Live vaccines: Increased risk of infection due to immunosuppression.

• Fatal neurotoxicity due to intrathecal administration remains a critical boxed warning in updated prescribing guidelines.
• WHO Essential Medicines List (latest edition) continues to list vincristine for leukemia and lymphomas.
• New pediatric protocols emphasize careful cumulative dosing to reduce long-term neuropathic complications.
• ASCO and NCCN guidelines underscore vincristine’s role in pediatric cancers, with caution on neuropathy.

• Temperature: Store at 2°C to 8°C (refrigerated).
• Light protection: Protect from light; use amber-colored vials or shielding.
• Do not freeze.
• Handling: Cytotoxic agent – use gloves, mask, and protective equipment.
• Reconstitution (if applicable): Follow manufacturer's guidance. Discard unused portions per hazardous waste protocol.