Table II.
Pharmacokinetics and drug interactions for tyrosine kinase inhibitors approved by the US Food and Drug Administration.
| Variable | Imatinib9 | Dasatinib16 | Nilotinib17 |
|---|---|---|---|
| Metabolism | CYP3A4* | CYP3A4* | CYP3A4* |
| Drug interactions | Avoid warfarin; systemic exposure to acetaminophen increases | Drug levels decreased by antacids, histamine2-receptor antagonists, and proton pump inhibitors | Avoid agents known to prolong QT interval† and strong CYP3A4 inhibitors |
| Contraindications | None | None | Hypokalemia, hypomagnesemia, long QT syndrome (risk of sudden death) |
| Elimination | Feces | Feces | Feces |
| Hepatic impairment | 25% Dose reduction with severe impairment | No dose adjustment | Consider alternative therapy if possible Child-Pugh class A and B: starting dose 400 mg PO morning/200 mg PO evening Child-Pugh class C: starting dose 200 mg PO BID |
| Renal impairment | CrCI 20–39 mL/min: 50% dose reduction (dose >400 mg not recommended) CrCI 40–59 mL/min: dose >600 mg not recommended |
Patients with impaired renal function excluded from studies | Patients with impaired renal function (Cr >1.5) excluded from studies |
| Use in pregnancy | Category D (avoid use) | Category D (avoid use) | Category D (avoid use) |
CYP = cytochrome P450; CrCI = creatinine clearance.
*
Concomitant strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital) may decrease plasma concentrations; concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase plasma concentrations and should be used with caution.
†
Amiodarone, disopyramide, procainamide, quinidine, sotalol, chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil, and pimozide.