The main drug-drug interactions associated with sunitinib include

CYP3A4 Inhibitors/ Inducers

CYP3A4 Inhibitors

No clinically significant interaction has been observed between vandetanib and itraconazole, a potent CYP3A4 inhibitor.1

CYP3A4 Inducers

Concomitant administration of the strong CYP3A4 inducer rifampicin resulted in a 40% reduction in exposure to vandetanib.1-3

QT Prolongators

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

CYP3A4 Substrates

There is no change in exposure for the CYP3A4 substrate, midazolam, when co-administered with vandetanib.1,2

P-glycoprotein Substrates

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

References

  1. Food and Drug Administration. Vandetanib (CAPRELSA) Prescribing information. 2015.
  2. European Medicines Agency. Vandetanib (CAPRELSA). Summary of Product Characteristics. 2015.
  3. 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.

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