Hepatic Impairment:Patients with mild and moderate hepatic impairment do not require a dose adjustment and should be treated per the recommended dose. A 25% decrease in the recommended dose should be used for patients with severe hepatic impairment [see Use in Specific Populations (8.6)].

Renal Impairment:Patients with moderate renal impairment (CrCL = 20-39 mL/min) should receive a 50% decrease in the recommended starting dose and future doses can be increased as tolerated.Doses greater than 600 mg are not recommended in patients with mild renal impairment (CrCL = 40-59 mL/min).For patients with moderate renal impairment doses greater than 400 mg are not recommended.

Imatinib should be used with caution in patients with severe renal impairment.A dose of 100 mg/day was tolerated in two patients with severe renal impairment.[See Use in Specific Populations (8.7)]

2.10 Dose Adjustment for Hepatotoxicity and Non-Hematologic Adverse Reactions
If elevations in bilirubin >3 x institutional upper limit of normal (IULN) or in liver transaminases >5 x IULN occur, Gleevec should be withheld until bilirubin levels have returned to a <1.5 x IULN and transaminase levels to <2.5 x IULN. In adults, treatment with Gleevec may then be continued at a reduced daily dose (i.e., 400 mg to 300 mg, 600 mg to 400 mg or 800 mg to 600 mg). In children, daily doses can be reduced under the same circumstances from 340 mg/m2/day to 260 mg/m2/day or from 260mg/m2/day to 200 mg/m2/day, respectively.

If a severe non-hematologic adverse reaction develops (such as severe hepatotoxicity or severe fluid retention), Gleevec should be withheld until the event has resolved. Thereafter, treatment can be resumed as appropriate depending on the initial severity of the event.

2.11 Dose Adjustment for Hematologic Adverse Reactions
Dose reduction or treatment interruptions for severe neutropenia and thrombocytopenia are recommended as indicated in Table 1.

Table 1Dose Adjustments for Neutropenia and Thrombocytopenia ASM associated with eosinophilia (starting dose 100 mg) ANC <1.0 x 109/L
and/or
platelets <50 x 109/L Stop Gleevec until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L

Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction)
 
HES/CEL with FIP1L1-PDGFRα fusion kinase (starting dose 100mg) ANC <1.0 x 109/L
and/or
platelets <50 x 109/L Stop Gleevec until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L

Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction)
 
Chronic Phase CML (starting dose 400 mg)

MDS/MPD, ASM and HES/CEL (starting dose 400 mg)

GIST (starting dose
400 mg) ANC <1.0 x 109/L
and/or
platelets <50 x 109/L Stop Gleevec until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L

Resume treatment with Gleevec at the original starting dose of 400 mg

If recurrence of ANC <1.0 x 109/L and/or platelets <50 x 109/L, repeat step 1 and resume Gleevec at a reduced doseof 300 mg
 
Ph+ CML : Accelerated Phase and Blast Crisis(starting dose 600 mg)
Ph+ ALL
(starting dose 600 mg) ANC <0.5 x 109/L
and/or
platelets <10 x 109/L Check if cytopenia is related to leukemia (marrow aspirate or biopsy)

If cytopenia is unrelated to leukemia, reduce dose of Gleevec to 400 mg

If cytopenia per