The main drug-drug interactions associated with sunitinib include
CYP3A4 Inhibitors/ Inducers
No clinically significant interaction has been observed between vandetanib and itraconazole, a potent CYP3A4 inhibitor.1
Concomitant administration of the strong CYP3A4 inducer rifampicin resulted in a 40% reduction in exposure to vandetanib.1-3
QTc Interval-Prolonging Drugs
Vandetanib prolongs the QT interval, hence, concomitant administration with products known to prolong the QT interval should be avoided. Co-administration with ondasetron has a small additive effect on prolongation of the QTc interval.1,2
Other Drug-drug Interactions
There is no change in exposure for the CYP3A4 substrate, midazolam, when co-administered with vandetanib.1,2
The AUC and Cmax for the P-glycoprotein substrate digoxin increased by 23% and 29% respectively, with vandetanib co-administration. The bradycardiac effect of digoxin may increase the risk for vandetanib QTc interval prolongation and Torsade de Points.1,2
Organic Cation 2 (OCT2) Transporter Substrates
The AUC and Cmax for metformin increased by 74% and 50% respectively, with vandetanib co-administration.1,2
- Food and Drug Administration. Vandetanib (CAPRELSA) Prescribing information. 2015.
- European Medicines Agency. Vandetanib (CAPRELSA). Summary of Product Characteristics. 2015.
- van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 2014; 15: e315-326.