Vandetanib

Class: Oral multikinase inhibitor (TKI)

Mechanism of Action

• Inhibits multiple receptor tyrosine kinases:
  • RET (rearranged during transfection proto-oncogene) → key driver in medullary thyroid cancer (MTC)
  • VEGFR-2, VEGFR-3 → anti-angiogenic activity
  • EGFR → additional tumor growth inhibition

Indications

• Advanced/metastatic medullary thyroid carcinoma (MTC) in adults (and sometimes pediatric ≥5 years under restricted programs).
• Not used for differentiated thyroid cancer.

Dosing (Adults)

• 300 mg PO once daily (with or without food)
• Swallow whole; if unable, can disperse in water

Pediatrics (≥5 years):

• Weight-based dosing (max 300 mg daily)

Key Toxicities & Monitoring

• Cardiac:
  • QT prolongation → torsades risk (boxed warning)
  • Monitor ECG and electrolytes (K, Mg, Ca) before and during therapy
• Hypertension (common, may require antihypertensives)
• Diarrhea, rash, acneiform eruption
• Interstitial lung disease/pneumonitis (rare, serious)
• Reversible posterior leukoencephalopathy syndrome (RPLS) – rare
• Myelosuppression (less common)

Drug Interactions

• QT-prolonging agents (e.g., amiodarone, sotalol, fluoroquinolones, ondansetron) → ↑ arrhythmia risk
• CYP3A4 inhibitors/inducers can affect vandetanib levels
• Acid-reducing agents ↓ absorption

Clinical Pearls for Pharmacists

• Dispensing is restricted under a REMS program due to QT prolongation risk.
• Baseline and regular ECGs are required; hold if QTc >500 ms.
• Long half-life (~19 days) → adverse effects may persist even after discontinuation.
• Advise patients to report palpitations, syncope, severe diarrhea, or neurologic symptoms promptly.