Vinorelbine Sandoz

Approved Indications:

• Non‑Small Cell Lung Cancer (NSCLC): Used in advanced (stage III/IV), recurrent, or metastatic NSCLC, as monotherapy or in combination with platinum-based agents (e.g., cisplatin). Also utilized as adjuvant therapy in resected disease under guideline protocols.
• Metastatic Breast Cancer: Indicated for patients relapsed or refractory to anthracyclines; used alone or in combination (e.g., with trastuzumab).

Clinically Accepted Off‑Label Uses:

• Recurrent or refractory ovarian cancer: As monotherapy or part of salvage regimens.
• Advanced pancreatic cancer and mesothelioma: Utilized in selected patients, often within clinical trials.

Route of Administration: Intravenous only. Must not be given intrathecally or by other routes.

Adults:

• Monotherapy: 25–30 mg/m² IV weekly.
• With Cisplatin (NSCLC): 25–30 mg/m² IV on days 1 and 8 of a 21-day cycle, plus cisplatin 100 mg/m² on day 1.

Elderly (≥70 years):

• Initiate at 20–25 mg/m² weekly; adjust based on tolerance and blood counts.

Pediatrics:

• Not routinely used; administered only in clinical trial settings.

Renal Impairment:

• No adjustment usually required; monitor CBC and fluid status.

Hepatic Impairment:

• Bilirubin 1.5–3 mg/dL: reduce dose by ~33%.
• Bilirubin >3 mg/dL: reduce dose by ~50% or withhold.

Administration Guidelines:

• Infuse slowly over 6–10 minutes via a running saline line.
• Ensure IV patency; avoid extravasation.
• Wear cytotoxic handling PPE; discard unused drug appropriately.

Vinorelbine tartrate is a semi-synthetic vinca alkaloid that binds to the tubulin β-subunit, inhibiting microtubule polymerization. This disrupts mitotic spindle formation during metaphase, arresting cell division (M-phase) and triggering apoptosis. Its selective action on mitotic microtubules reduces neurotoxicity compared to earlier vinca compounds.

• Absorption: Not absorbed orally; intravenous administration only.
• Distribution: Rapid and extensive; large volume (20–40 L/kg); crosses little into CNS.
• Protein Binding: 80–90%.
• Metabolism: Hepatic via CYP3A4 into active (4-O-deacetylvinorelbine) and inactive metabolites.
• Half-life: Biphasic, with a terminal half-life of 27–43 hours.
• Elimination: Primarily biliary and fecal (~70%), with <20% renal excretion.

• Pregnancy: Contraindicated. Teratogenic and embryotoxic; may cause fetal harm. Effective contraception recommended during treatment and for at least 3 months after.
• Lactation: Contraindicated. Likely excreted in breast milk; risk of serious infant toxicity.
• Fertility: May impair reproductive function in both sexes; fertility preservation should be discussed.

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

• Hypersensitivity to vinorelbine or vinca alkaloids
• Severe neutropenia (ANC <1,500/mm³) or thrombocytopenia
• Pregnancy and breastfeeding
• Intrathecal administration
• Hepatic impairment with bilirubin >3 mg/dL

• Severe neutropenia: Monitor CBC prior to each dose; delay treatment for ANC <1,000/mm³.
• Hepatic impairment: Adjust dose or withhold in severe dysfunction.
• Neurotoxicity: Mild to moderate neuropathy may occur; monitor for paresthesia.
• Pulmonary toxicity: Rare interstitial pneumonitis or fibrosis observed—monitor symptoms.
• Gastrointestinal toxicity: May cause constipation or ileus—consider prophylactic laxatives.
• Extravasation risk: Irritant; manage promptly.
• Black box warning: Fatal if administered intrathecally.
• Elderly patients: Higher risk of hematologic and non-hematologic toxicities; monitor closely.

Common (≥10%):

• Hematologic: Neutropenia, anemia, thrombocytopenia
• Gastrointestinal: Constipation, nausea, vomiting, anorexia
• Neurologic: Peripheral neuropathy—paresthesia
• General: Fatigue, asthenia, injection-site reactions

Serious or Rare:

• Febrile neutropenia
• Paralytic ileus
• Interstitial pneumonitis/pulmonary fibrosis
• SIADH (rare)
• Severe infections and sepsis
• Anaphylactoid reactions
• Cardiovascular events (rare: chest pain, arrhythmia)

Timing & Dose Dependence:

• Neutropenia peaks ~day 7–10. GI effects may begin within 24–48 hours; neuropathy is cumulative.

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May increase toxicity—avoid or adjust dose.
• CYP3A4 inducers (e.g., rifampin, phenytoin): May reduce efficacy.
• Other myelosuppressive drugs: Additive effect on bone marrow suppression.
• Live vaccines: Avoid during and after treatment due to immunosuppression.
• Verapamil/diltiazem: Can alter vinorelbine levels via CYP3A4 modulation.
• Grapefruit juice / alcohol: Potential CYP3A4 interaction; best avoided.

• Regulatory guidance (FDA/EMA): Reaffirmed Black Box warning on intrathecal fatality and updated hepatic dose adjustments.
• ASCO/NCCN: Endorsed vinorelbine as suitable for elderly NSCLC patients due to its tolerability profile.
• Investigational use: Ongoing trials of oral vinorelbine and combined regimens with targeted therapies in lung and breast cancers.

• Temperature: Store refrigerated at 2–8 °C; do not freeze.
• Light: Protect from light using amber vials or foil wrapping.
• Handling: Cytotoxic agent—use PPE, gloves, gown, eye protection.
• Dilution Stability: Once diluted with 0.9% saline or 5% dextrose, stable up to 24 hours refrigerated. Administer as soon as practical.
• Disposal: Follow local hazardous drug waste regulations.