Vinblast

Approved Indications:

• Hodgkin’s Lymphoma: Used as part of combination chemotherapy regimens (e.g., ABVD) for the treatment of Hodgkin's disease, including all stages.
• Non-Hodgkin’s Lymphoma (NHL): Indicated in the treatment of lymphocytic, histiocytic, and mixed-cell types.
• Testicular Cancer: Approved for use in metastatic testicular carcinoma as part of combination regimens (e.g., PVB protocol: Cisplatin, Vinblastine, Bleomycin).
• Kaposi’s Sarcoma (HIV-negative): Used in classical or endemic forms of Kaposi's sarcoma.
• Breast Cancer: Occasionally used in advanced or metastatic breast cancer unresponsive to hormonal therapy.
• Choriocarcinoma and Gestational Trophoblastic Neoplasia: May be used as second-line or adjunctive therapy.
• Langerhans Cell Histiocytosis (LCH): Used off-label in pediatric and adult LCH.
• Mycosis Fungoides (Cutaneous T-cell Lymphoma): Used off-label in advanced or refractory cases.

Route of Administration:

• Intravenous (IV) use only. Must never be administered intrathecally, as it can cause fatal neurotoxicity.

Adults:

• Initial Dose: 3.7 mg/m² IV once weekly.
• Subsequent Doses: May be increased gradually by 0.6 mg/m² weekly, up to a maximum of 5–6 mg/m², depending on tolerance and hematologic response.
• Maintenance Dose: Typically 3–5 mg/m² once weekly, adjusted based on WBC and platelet counts.

Pediatrics:

• Initial Dose: 2.5 mg/m² or 0.1 mg/kg once weekly.
• Dose Adjustment: Based on hematologic tolerance and tumor response.

Elderly:

• Use with caution; begin at the lower end of the dosing range due to increased risk of bone marrow suppression.

Renal Impairment:

• No dosage adjustment usually needed; monitor hematologic parameters carefully.

Hepatic Impairment:

• Reduce dose by 50% if bilirubin is 1.5–3 mg/dL.
• Reduce dose by ≥75% if bilirubin >3 mg/dL.
• Contraindicated in severe hepatic dysfunction due to decreased clearance and risk of toxicity.

Administration Notes:

• Administer via IV push or short infusion into a free-flowing IV line.
• Avoid extravasation; if it occurs, local injection of hyaluronidase and warm compresses may reduce tissue damage.

Vinblastine sulfate is a vinca alkaloid that binds to tubulin and inhibits microtubule formation in the mitotic spindle, thereby arresting cell division during metaphase. This disruption of the microtubule dynamics inhibits mitosis and eventually leads to cell death, particularly affecting rapidly dividing malignant cells. Unlike other cell-cycle nonspecific agents, vinblastine exerts its cytotoxic effects during the M-phase of the cell cycle.

• Absorption: Not absorbed orally; must be administered intravenously.
• Distribution: Widely distributed in tissues; high affinity for platelets and cellular elements; crosses the blood-brain barrier poorly.
• Protein Binding: ~80% to serum proteins.
• Metabolism: Extensively metabolized in the liver, primarily via CYP3A4 enzymes.
• Active Metabolites: Several, including desacetylvinblastine, which has limited clinical significance.
• Elimination Half-life: Biphasic; terminal half-life ranges from 24 to 36 hours.
• Excretion: ~10–20% via urine; ~40–50% via feces (biliary excretion). Renal elimination is not the major pathway.

• Pregnancy:
• FDA Category (old system): Category D.
• Risks: Known teratogenic in animal studies; may cause fetal harm. Use only if benefits outweigh potential fetal risks, especially in life-threatening cancers.
• Lactation:
• Excretion in human milk is unknown; however, due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during therapy and for several days after treatment ends.

• Primary Class: Antineoplastic Agent
• Subclass: Vinca Alkaloid (Microtubule Inhibitor)

• Known hypersensitivity to vinblastine or any component of the formulation
• Severe bone marrow suppression
• Intrathecal administration (strictly contraindicated due to fatal neurotoxicity)
• Significant hepatic dysfunction
• Active infection not under control

• Fatal Intrathecal Use Warning: Intrathecal administration of vinblastine is fatal; it should be labeled and handled with utmost caution.
• Bone Marrow Suppression: Dose-limiting toxicity; monitor WBC, platelet, and RBC counts regularly.
• Neurotoxicity: May cause peripheral neuropathy, including paresthesia, hyporeflexia, and motor weakness.
• Extravasation Risk: Vesicant; can cause severe local tissue necrosis—ensure proper IV access before administration.
• Hepatic Impairment: Increases risk of toxicity due to reduced clearance.
• Pulmonary Toxicity: Rare cases of bronchospasm and dyspnea reported.
• Constipation & Ileus: Gastrointestinal toxicity, including paralytic ileus, particularly in children; monitor closely.

Common Adverse Effects:

• Hematologic: Leukopenia, neutropenia, thrombocytopenia
• Gastrointestinal: Nausea, vomiting, constipation, abdominal pain
• Neurologic: Peripheral neuropathy, muscle weakness, jaw pain
• Dermatologic: Alopecia

Serious or Rare Adverse Effects:

• Pulmonary: Bronchospasm, dyspnea, interstitial pneumonitis (rare)
• Neurologic: Severe autonomic neuropathy, including paralytic ileus or urinary retention
• Infection Risk: Due to immunosuppression
• Extravasation Injury: Severe local tissue necrosis and ulceration

Timing & Dose Dependency:

• Hematologic suppression is dose-limiting and may occur 4–10 days after dosing.
• Neurological symptoms may develop gradually and are dose-cumulative.

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): Increase vinblastine plasma levels and toxicity.
• CYP3A4 Inducers (e.g., rifampin, phenytoin): Reduce efficacy by increasing metabolism.
• Azole Antifungals (e.g., itraconazole): May enhance neurotoxicity and myelosuppression.
• Neurotoxic Agents (e.g., cisplatin): Additive peripheral neuropathy.
• Myelosuppressive Drugs: Increased risk of hematologic toxicity when used concurrently.
• Live Vaccines: Immunosuppression may reduce vaccine efficacy and increase risk of infection.

• Labeling Emphasis: Reinforced boxed warnings regarding fatal outcomes from intrathecal administration.
• Updated Pediatric Guidelines: WHO and pediatric oncology groups continue to recommend vinblastine as part of protocols for pediatric Hodgkin’s lymphoma and Langerhans cell histiocytosis.
• EMA and FDA Monitoring: Continuous pharmacovigilance for signs of cumulative neurotoxicity and hepatic injury in long-term use.

• Temperature: Store between 2°C to 8°C (36°F to 46°F); refrigerate; do not freeze.
• Light Protection: Protect from light; keep in original packaging until use.
• Handling Precautions: Use gloves and protective equipment; avoid direct contact with skin or mucous membranes.
• Reconstitution/Stability:
• Once diluted, stable at room temperature for up to 24 hours.
• Discard any unused solution per cytotoxic waste disposal protocols.