Table 6: Pharmacokinetic interactions of BCR/ABL inhibitors.
BCRP: breast cancer resistance protein.
UGT: uridinglucuronyl transferase.
Mechanism BCR/ABL inhibitor Drug Consequences/Recommendations
Potent CYP3A4 inhibitors All Boceprevir, clarithromycin, itraconazole, ketoconazole, lopinavir / ritonavir, nefazodone, nelfinavir, indinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole, grape fruit juice. Increased concentrations of BCR/ABL inhibitor. Avoid.
Moderate CYP3A4 inhibitors All Amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir / ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, crizotinib, imatinib, verapamil, fruit juice. Increased concentrations of BCR/ABL inhibitor. Avoid high doses.
Potent CYP3A4 inducers All Carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifampin, rifabutin, St. John's Wort. Reduced concentrations of BCR/ABL inhibitor. Avoid.
Moderate CYP3A4 inducers All Bosentan, dexamethasone, efavirenz, etravirine, modafinil, nafcillin, nevirapine. Reduced concentrations of BCR/ABL inhibitor. Consider increasing the dose of the BCR/ABL inhibitor.
Potent P-glycoprote ininhibitors Imatinib, nilotinib, ponatinib Amiodarone, azithromycin, captopril, carvedilol, clarithromycin, cyclosporine, diltiazem, dronedarone, erythromycin, felopdipine, itraconazole, ketoconazole, lopinavir, ritonavir, quercetin, quinidine, verapamil. Increased concentrations of BCR/ABL inhibitor. Avoid.
Potent P-glycoprotein inducers Imatinib, nilotinib, ponatinib Carbamazepine, phenytoin, St. John's Wort, tipranavir/ritonavir. Reduced concentrations of BCR/ABL inhibitor. Avoid.
Potent BCRP inhibitors Ponatinib Cyclosporine eltrombopag, gefitinib Increased concentrations of ponatinib. Exercise caution.
CYP3A4 substrates Dasatinib, imatinib, nilotinib, ponatinib Alfentanil, aprepitant, astemizole, budesonide, buspirone, cisapride, cyclosporine, conivaptan, darifenacin, darunavir, dronedarone, eletriptan, eplerenome, ergotamine, everolimus, felodipine, fentanyl, fluticasone, indinavir, lopinavir, lovastatin, lurasidone, maraviroc, midazolam, nifedipine, nisoldipine, pimozide, quetiapine, saquinavir, sildenafil, somvastatin, sirolimus, tolvaptan, tipranavir, triazolam, vardenafil, triazolam. Increased concentrations of CYP3A4 substrates with an increased risk of toxicity. Avoid drugs with reduced therapeutic index. Exercise caution with the rest.
CYP2C9 substrates Dasatinib, imatinib, nilotinib Acenocoumarol, celecoxib, diclofenac, phenytoin, warfarin, S-warfarin, tolbutamide. Increased concentrations of CYP2C9 substrates with an increased risk of toxicity. Avoid drugs with reduced therapeutic index. Exercise caution with the rest.
2D6 substrates Imatinib, nilotinib Amitriptyline, aripiprazole, atomoxetine, carisoprodol, clomipramine, chlorpromazine, duloxetine, codeine, dextromethorphan, flecainide, haloperidol, imipramine, metoprolol, metoclopramide, mexiletine, mirtazapine, nevibolol, olanzapine, paroxetine, perphenazine, propafenone, R-warfarin, risperidone, tamoxifen, thioridazine, tolterodinetramadol, venlafaxine. Increased concentrations of 2D6 substrates with an increased risk of toxicity. Avoid drugs with reduced therapeutic index. Exercise caution with the rest.
CYP2C8 substrates Imatinib, nilotinib Rosiglitazone, pioglitazone, repaglinide, paclitaxel. Increased concentrations of CYP2C8 substrates with an increased risk of toxicity. Avoid drugs with reduced therapeutic index. Exercise caution with the rest.
P-glycoprotein substrates Imatinib, nilotinib, ponatinib Aliskiren, ambrisentan, cyclosporine, colchicine, dabigatran, digoxin, everolimus, phenoxyphenadine, indinavir, maraviroc, nilotinib, paclitaxel, posaconazole, pravastatin, ritonavir, saxagliptin, sirolimus, sitagliptin, tolvactan, topotecan, verapamil, vincristine. Increased concentrations of P-glycoprotein substrates with an increased risk of toxicity. Avoid drugs with reduced therapeutic index. Exercise caution with the rest.
BCRP substrates Dasatinib, imatinib, nilotinib, ponatinib Daunorubicin, doxorubicin, lapatinib, methotrexate, mitoxantrone, irinotecan, rosuvastatin, sulfasalazine, topotecan. Increased concentrations of BCRP substrates with an increased risk of toxicity. Avoid drugs with reduced therapeutic index. Exercise caution with the rest.
UGT1A1 substrates Nilotinib Atazanavir, dolutegravir, erlotinib, iritotecan, raltegravir. Increased concentrations of UGT1A1 substrates with an increased risk of toxicity. Avoid drugs with reduced therapeutic index. Exercise caution with the rest.
UGT1A1 inhibitors Nilotinib Atazanavir, dolutegravir, efavirenz, ketoconazole, pazopanib, zafirlukast. Increased concentrations of nilotinib with an increased potential for toxicity.