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Drug-Drug Interactions (DDIs) Associated with Kinase Inhibitors: General Introduction

This online resource provides guidance on how to safely manage drug-drug interactions with kinase inhibitors. This section cannot recommend whether a kinase inhibitor can be administered with another drug as the quality of evidence is generally low. In addition, it is extremely important that there is good communication between the prescribing oncologist and the (clinical) pharmacist and that everyone knows exactly what other medications the patient is taking (including herb- and over the counter drugs). It is also important that during medication review the pharmacist uses a program that sensitively detect potential harmful drug interactions. If a potential DDI is detected healthcare professionals must collaborate to adequately manage such a DDI.

The overall recommendations, clinical pharmacology, pharmacokinetics and key drug-drug interactions for each the eight most-commonly used kinase inhibitors for key tumour types will be explored. Further information on each aspect can be found by clicking on each kinase inhibitor:

Information on overall recommendations, clinical pharmacology, pharmacokinetics and key drug-drug interactions for each of the eight commonly-used kinase inhibitors can also be found by clicking on each type of drug-drug interaction below. As CYP3A4 inducers/inhibitors, QT prolongators and drug-drug interactions with acid-reducing agents are the three most clinically important types of drug-drug interactions associated with kinase inhibitors, information regarding these on a more extensive list of drugs can be found on these pages:

A drug interaction is the pharmacological or clinical response to the administration or co-exposure of a drug with another substance that modifies their pharmacokinetics or the patient’s response to the drug.1-4 When the co-administered substance is another drug, it is referred to as a drug–drug interaction.3 The occurrence of drug interactions is clinically relevant, as they can:3,4

  1. Increase or decrease therapeutic response.
  2. Cause a response that does not occur with the use of either agent alone.
  3. Reinforce or intensify an adverse event.

Drug interactions are generally classified as either pharmacokinetic or pharmacodynamics in nature, or as a combination of the two mechanisms1-3

Pharmacokinetic Drug Interactions

Pharmacodynamic Drug Interactions

Interactions that alter the absorption, distribution, metabolism, elimination and transport of a drug and are often the result of effects exerted by P450 enzymes.

An additive, synergistic or antagonistic effect, which influences drug response and is caused by the use of drugs with similar mechanisms of action or similar molecular targets.

References

  1. Mathijssen RH, Sparreboom A, Verweij J. Determining the optimal dose in the development of anticancer agents. Nat Rev Clin Oncol 2014; 11: 272-281.
  2. 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.
  3. Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer 2006; 6: 546-558.
  4. Buajordet I, Ebbesen J, Erikssen J et al. Fatal adverse drug events: the paradox of drug treatment. J Intern Med 2001; 250: 327-341.

Pharmacodynamics

Overview of drug-drug interactions associated that alter the pharmacodynamics, specifically QTc prolongation, of kinase inhibitors

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