Vandetanib

Category Immunomodulatory Drugs and Cytokines

Clinical Pharmacology

Mechanism of Action1,2

Vandetanib inhibits Epidermal growth factor receptor (EGFR), Vascular endothelial growth factor receptors (VEGFRs), rearranged during transfection (RET), protein tyrosine kinase 6 (BRK), TIE2, members of the EPH receptors kinase family and members of the Src family of tyrosine kinases. Vandetanib also inhibits Epidermal growth factor (EGF)-stimulated Receptor tyrosine kinase phosphorylation and VEGF-stimulated Tyrosine kinase phosphorylation. Vandetanib inhibits Angiogenesis, tumour cell permeability and tumour growth and metastasis.

Indication1,2

Symptomatic or progressive medullary thyroid cancer.

Indolent, asymptomatic or slowly-progressing disease.

Recommended dosage1,2

300 mg/day.

Pharmacokinetics

Overview

In medullary thyroid cancer patients given the 300-mg dose, the mean clearance of vandetanib was ~13.2 litres/hour, with a mean volume of distribution of ~7,450 litres, and a median plasma half-life of 19 days.1,2

Absorption and Distribution

Peak plasma concentrations occur within a median of 6 hours (range 4-10 hours), following oral administration vandetanib.1,2 On multiple dosing, vandetanib accumulates approximately 8-fold. Vandetanib binds to human serum albumin and a1-acid-glycoprotein with binding of approximately 90%.1,2

Metabolism and Elimination

Following oral dosing of 14C- vandetanib, unchanged vandetanib and metabolites vandetanib N-oxide and N-desmethyl vandetanib were detected in plasma, urine and faeces.1,2 Vandetanib is metabolised primarily by CYP3A4 and flavin-containing monooxygenase enzymes FM01 and FM03.1,2

Clearance of vandetanib is approximately 13.2 litres/hour with a plasma half-life of approximately 19 days. Elimination is primarily via faeces (44%) and urine (25%). Excretion is expected to occur beyond 21 days based on the plasma half-life.1,2

References

  1. Food and Drug Administration. Vandetanib (CAPRELSA) Prescribing information. 2015.
  2. European Medicines Agency. Vandetanib (CAPRELSA). Summary of Product Characteristics. 2015.

The Summary of Product Characteristics should be reviewed before prescribing any medication.

Last update: 01 July 2015