Vinorelbine

Class: Vinca alkaloid (semisynthetic derivative of vinblastine)

Formulation: IV (solution, injection), Oral capsules (less common, not available everywhere).

Mechanism of Action (MOA):

• Binds to β-tubulin, inhibiting microtubule assembly.
• Prevents mitotic spindle formation → M-phase arrest → apoptosis.
• More selective for mitotic microtubules vs. neuronal → less neurotoxicity than vincristine.

Indications:

• Non–Small Cell Lung Cancer (NSCLC) (alone or with cisplatin).
• Breast cancer (metastatic or advanced).
• Ovarian cancer, Hodgkin’s/Non-Hodgkin’s lymphoma (off-label).

Dosing:

• IV: 25–30 mg/m² IV weekly (NSCLC, breast cancer).
• Oral (where available): 60–80 mg/m² weekly.
• Pediatric: Rare/off-label, mainly investigational.
• Dose adjustment:
  • Reduce in hepatic impairment (based on bilirubin/AST).
  • No renal dose adjustment required.

Toxicities:

🔹 Dose-limiting toxicity: Myelosuppression (neutropenia)

• More pronounced than with vincristine.

🔹 Other toxicities:

• Neuropathy (less frequent/severe vs. vincristine).
• Constipation, nausea, vomiting.
• Alopecia.
• SIADH (rare).
• Vesicant → extravasation risk.

Contraindications / Warnings:

• Never administer intrathecally (fatal).
• Avoid strong CYP3A4 inhibitors (azole antifungals, clarithromycin, protease inhibitors) → ↑ toxicity.
• Hepatic impairment increases risk of toxicity.

Clinical Pearls for Pharmacists:

• Compared to other vinca alkaloids:
  • Vincristine → neurotoxicity
  • Vinblastine → myelosuppression
  • Vinorelbine → neutropenia (dose-limiting)
• Safer neurologic profile → useful in elderly patients with lung cancer.
• Oral formulation available in some regions (convenience vs. adherence challenges).
• Proactive infection monitoring and growth factor support may be required in neutropenic patients.