The main drug-drug interactions associated with imatinib include
CYP3A4 Inhibitors/ Inducers
Concomitant use of imatinib with CYP3A4 inhibitors may decrease metabolism and increase imatinib concentrations.1 Examples include: protease inhibitors such as indinavir, lopinavir/ritonavir, saquinavir, telaprevir, boceprevir; azole antifungals such as ketoconazole, itraconazole, posaconazole, voriconazole; macrolides such erythromycin, clarithromycin and telithromycin.1 Ketoconazole for example, increased exposure to imatinib with an increase in Cmax and AUC of imatinib of 36% and 40%, respectively.1
Concomitant administration of imatinib with CYP3A4 inducers may decrease exposure to imatinib, increasing the risk of treatment failure. Examples include dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital, fosphenytoin, primidone or St. John’s wort.1 The anti-epileptic drugs carbamazepine, rifampicin and phenytoin have been shown to reduce imatinib plasma levels by approximately 70%.2
Other Drug-drug Interactions
Imatinib and Antineoplastic Agents
Drug-drug interactions between imatinib and chemotherapy are not well characterised. Concomitant use with L-asparaginase could be associated with increased hepatoxicity. 1
See also CYP3A4 substrates below.
Imatinib increases the Cmax and AUC of the CYP3A4 substrate simvastin, 2- and 3.5-fold, respectively. Caution should therefore be used when co-administering imatinib with CYP3A4 substrates with a narrow therapeutic index such as cyclosporine, pimozide, tacrolimus, sirolimus, ergotamine, diergotamine, fentanyl, alfentanil, terfenadine, bortezomib, docetaxel and quinidine. Imatinib may also increase plasma concentrations of other CYP3A4 metabolised drugs such as triazolo-benzodiazepines, dihydropyridine calcium channel blockers and certain HMB-CoA reductase inhibitors such as statins.1
Imatinib inhibits CYP2D6 activity, for example the Cmax and AUC of metoprolol is increased by ~23% with imatinib.1
There is an increased bleeding risk when taking imatinib with warfarin, due to competition with cytochrome P450 isoenzymes 3
- European Medicines Agency. Imatinib (GLIVEC). Summary of Product Characteristics. 2015.
- Pajares B, Torres E, Trigo JM et al. Tyrosine kinase inhibitors and drug interactions: a review with practical recommendations. Clin Transl Oncol 2012; 14: 94-101.
- 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.