Imatinib
Dosing in kidney impairment
Renal Impairment The effect of renal impairment on the pharmacokinetics of imatinib was assessed in 59 patients with cancer and varying degrees of renal impairment at single and steady state imatinib doses ranging from 100 to 800 mg/day. The mean exposure to imatinib (dose normalized AUC) in patients with mild and moderate renal impairment increased 1.5- to 2-fold compared to patients with normal renal function.
There are not sufficient data in patients with severe renal impairment [see Clinical Pharmacology] . Dose reductions are necessary for patients with moderate and severe renal impairment [ see Dosage and Administration ]. Table 17: Renal Function Classification Renal dysfunction Renal function tests Mild CrCL = 40 to 59 mL/min Moderate CrCL = 20 to 39 mL/min Severe CrCL = less than 20 mL/min Abbreviation: CrCL, creatinine clearance.
Dosing in liver impairment
Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of both imatinib and its major metabolite, CGP74588, was assessed in 84 patients with cancer with varying degrees of hepatic impairment at imatinib doses ranging from 100 mg to 800 mg. Mild and moderate hepatic impairment do not influence exposure to imatinib and CGP74588.
In patients with severe hepatic impairment, the imatinib C max and area under curve (AUC) increased by 63% and 45% and the CGP74588 C max and AUC increased by 56% and 55%, relative to patients with normal hepatic function [see Clinical Pharmacology ]. Reduce the dose by 25% for patients with severe hepatic impairment [ see Dosage and Administration ].
Table 16: Liver Function Classification Liver function test Normal (n = 14) Mild (n = 30) Moderate (n = 20) Severe (n = 20) Total bilirubin less than or equal to ULN greater than 1.0 to 1.5 times the ULN greater than 1.5 to 3 times the ULN greater than 3 to 10 times the ULN SGOT less than or equal to ULN greater than ULN (can be normal if Total Bilirubin is greater than ULN) Any Any Abbreviation: SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); ULN, upper limit of normal for the institution.
| Adults with Ph+ CML CP (2.2): | 400 mg/day |
| Adults with Ph+ CML AP or BC (2.2): | 600 mg/day |
| Pediatrics with Ph+ CML CP (2.3): | 340 mg/m2/day |
| Adults with Ph+ ALL (2.4): | 600 mg/day |
| Pediatrics with Ph+ ALL (2.5) | 340 mg/m2/day |
| Adults with MDS/MPD (2.6): | 400 mg/day |
| Adults with ASM (2.7): | 100 mg/day or 400 mg/day |
| Adults with HES/CEL (2.8): | 100 mg/day or 400 mg/day |
| Adults with DFSP (2.9): | 800 mg/day |
| Adults with metastatic and/or unresectable GIST (2.10): | 400 mg/day |
| Adjuvant treatment of adults with GIST (2.11): | 400 mg/day |
| Patients with mild to moderate hepatic impairment (2.12): | 400 mg/day |
| Patients with severe hepatic impairment (2.12): | 300 mg/day |
Preparation and administration
Drug Administration The prescribed dose should be administered orally, with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. For patients unable to swallow the film-coated tablets, the tablets may be dispersed in a glass of water or apple juice.
The required number of tablets should be placed in the appropriate volume of beverage (approximately 50 mL for a 100-mg tablet, and 200 mL for a 400-mg tablet) and stirred with a spoon. The suspension should be administered immediately after complete disintegration of the tablet(s). For daily dosing of 800 mg and above, dosing should be accomplished using the 400-mg tablet to reduce exposure to iron.
Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.