Drugs that may alter imatinib plasma concentrations
Drugs that may increase imatinib plasma concentrations:
Caution is recommended when administering Gleevec with inhibitors of the CYP3A4 family (e.g., ketoconazole,
itraconazole, erythromycin, clarithromycin). Substances that inhibit the cytochrome P450 isoenzyme (CYP3A4) activity
may decrease metabolism and increase imatinib concentrations. There is a significant increase in exposure to imatinib
when Gleevec is coadministered with ketoconazole (CYP3A4 inhibitor).
Drugs that may decrease imatinib plasma concentrations:
Substances that are inducers of CYP3A4 activity may increase metabolism and decrease imatinib plasma concentrations.
Co-medications that induce CYP3A4 (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, phenobarbital or St.
Johns Wort) may significantly reduce exposure to Gleevec. Pretreatment of healthy volunteers with multiple doses of
rifampin followed by a single dose of Gleevec, increased Gleevec oral-dose clearance by 3.8-fold, which significantly
(p<0.05) decreased mean cmax and AUC(0-8). In patients where rifampin or other CYP3A4 inducers are
indicated, alternative therapeutic agents with less enzyme induction potential should be considered.
Drugs that may have their plasma concentration altered by Gleevec
Gleevec increases the mean cmax and AUC of simvastatin (CYP3A4 substrate) 2- and 3.5-fold,
respectively, suggesting an inhibition of the CYP3A4 by Gleevec. Particular caution is recommended when administering
Gleevec with CYP3A4 substrates that have a narrow therapeutic window (e.g., cyclosporine or pimozide). Gleevec will
increase plasmaconcentration of other CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine
calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.).
Because warfarin is metabolized by CYP2C9 and CYP3A4, patients who require anticoagulation should receive
low-molecular weight or standard heparin.
in vitro, Gleevec inhibits the cytochrome P450 isoenzyme CYP2D6 activity at similar concentrations that
affect CYP3A4 activity. Systemic exposure to substrates of CYP2D6 is expected to be increased when coadministered
with Gleevec. No specific studies have been performed and caution is recommended.
in vitro, Gleevec inhibits acetaminophen O-glucuronidation (Ki value of 58.5 µM) at therapeutic
levels. Systemic exposure to acetaminophen is expected to be increased when coadministered with Gleevec. No specific
studies in humans have been performed and caution is recommended.