Clinically relevant drug interactions with multikinase inhibitors: a review.

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Hussaarts KGAM, Veerman GDM, Jansman FGA, van Gelder T, Mathijssen RHJ, van Leeuwen RWF

Clinically relevant drug interactions with multikinase inhibitors: a review.

Ther Adv Med Oncol. 2019 Jan 4;11:1758835918818347. doi: 10.1177/1758835918818347. eCollection 2019.

PubMed ID

30643582 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Lenvatinib	P-glycoprotein 1	Protein	Humans	No	Substrate Inhibitor	Details
Lenvatinib	Solute carrier organic anion transporter family member 1B3	Protein	Humans	Unknown	Inhibitor	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Ceritinib Methimazole	The metabolism of Ceritinib can be decreased when combined with Methimazole.
Ceritinib Midostaurin	The metabolism of Ceritinib can be decreased when combined with Midostaurin.
Ceritinib Danazol	The metabolism of Ceritinib can be decreased when combined with Danazol.
Ceritinib Ritonavir	The metabolism of Ceritinib can be decreased when combined with Ritonavir.
Ceritinib Voriconazole	The metabolism of Ceritinib can be decreased when combined with Voriconazole.