Clinically relevant drug interactions with multikinase inhibitors: A review

Koen G. A. M. Hussaarts*, G. D. Marijn Veerman, Frank G. A. Jansman, Teun van Gelder, Ron H. J. Mathijssen, Roelof W. F. van Leeuwen

*Bijbehorende auteur voor dit werk

    Onderzoeksoutput: Review articlepeer review

    59 Citaten (Scopus)
    128 Downloads (Pure)


    Multikinase inhibitors (MKIs), including the tyrosine kinase inhibitors (TKIs), have rapidly become an established factor in daily (hemato)-oncology practice. Although the oral route of administration offers improved flexibility and convenience for the patient, challenges arise in the use of MKIs. As MKIs are prescribed extensively, patients are at increased risk for (severe) drug-drug interactions (DDIs). As a result of these DDIs, plasma pharmacokinetics of MKIs may vary significantly, thereby leading to high interpatient variability and subsequent risk for increased toxicity or a diminished therapeutic outcome. Most clinically relevant DDIs with MKIs concern altered absorption and metabolism. The absorption of MKIs may be decreased by concomitant use of gastric acid-suppressive agents (e.g. proton pump inhibitors) as many kinase inhibitors show pH-dependent solubility. In addition, DDIs concerning drug (uptake and efflux) transporters may be of significant clinical relevance during MKI therapy. Furthermore, since many MKIs are substrates for cytochrome P450 isoenzymes (CYPs), induction or inhibition with strong CYP inhibitors or inducers may lead to significant alterations in MKI exposure. In conclusion, DDIs are of major concern during MKI therapy and need to be monitored closely in clinical practice. Based on the current knowledge and available literature, practical recommendations for management of these DDIs in clinical practice are presented in this review.

    Originele taal-2English
    Aantal pagina's34
    TijdschriftTherapeutic advances in medical oncology
    Vroegere onlinedatum4-jan.-2019
    StatusPublished - jan.-2019

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