vandetanib: clinical use

Prescribing considerations

• Confirm a RET mutation with a validated test before initiation; available evidence indicates insufficient activity when no RET mutation is identified.
• Initiation and supervision require expertise in medullary thyroid cancer, anti-cancer therapy and ECG interpretation.
• Assess cardiovascular history, blood pressure, renal and hepatic function, electrolyte disturbance, diarrhoea risk, aneurysm history and planned major surgery.
• Provide and discuss the patient alert card. Consider vandetanib's long persistence when managing toxicity or interactions.

Contraindications and cautions

• Hypersensitivity to vandetanib or an excipient.
• Congenital long-QT syndrome or a pretreatment QTc interval above the product threshold.
• Concomitant use with specified medicines that prolong QT or induce torsades de pointes.
• Breastfeeding.

Monitoring

• Baseline and serial ECGs, with potassium, magnesium, calcium and thyroid-stimulating hormone.
• Blood pressure, renal function and hydration; intensify assessment during diarrhoea or dehydration.
• Periodic liver-function testing, particularly alanine aminotransferase.
• Assess new respiratory symptoms promptly for interstitial lung disease and neurological symptoms for posterior reversible encephalopathy syndrome.

Clinical pharmacology

Vandetanib inhibits RET, VEGFR-2, EGFR and, less strongly, VEGFR-3 tyrosine kinases. It has extensive distribution and protein binding, partial CYP3A4 metabolism and a plasma half-life of about 19 days; exposure rises with renal impairment.

Formulation and product differences

• The selected presentation is a film-coated oral tablet.
• The tablet can be dispersed in still water without crushing and the resulting dispersion can be administered through an appropriate feeding tube.

Tablet

Route: Oral

Strengths: 100 mg, 300 mg