DOSAGE AND ADMINISTRATION
Therapy should be initiated by a physician experienced in the treatment of patients with chronic myeloid leukemia or gastrointestinal stromal tumors.
The recommended dosage of Gleevec® (imatinib mesylate) is 400 mg/day for adult patients in chronic phase CML and 600 mg/day for adult patients in accelerated phase or blast crisis. The recommended Gleevec dosage is 260 mg/m2/day for children with Ph+ chronic phase CML recurrent after stem cell transplant or who are resistant to interferon-alpha therapy. The recommended dosage of Gleevec is 400 mg/day or 600 mg/day for adult patients with unresectable and/or metastatic, malignant GIST.
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.
In children, Gleevec treatment can be given as a once-daily dose or alternatively the daily dose may be split into two - once in the morning and once in the evening. There is no experience with Gleevec treatment in children under 3 years of age.
Patients with mild and moderate hepatic impairment should be treated at a starting dose of 400 mg/day. Patients with severe hepatic impairment should be treated at a starting dose of 300 mg/day. (See CLINICAL PHARMACOLOGY and PRECAUTIONS)
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).
Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.
In CML, a dose increase from 400 mg to 600 mg in adult patients with chronic phase disease, or from 600 mg to 800 mg (given as 400 mg twice daily) in adult patients in accelerated phase or blast crisis may be considered in the absence of severe adverse drug reaction and severe non-leukemia related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time), failure to achieve a satisfactory hematologic response after at least 3 months of treatment, failure to achieve a cytogenetic response after 6-12 months of treatment, or loss of a previously achieved hematologic or cytogenetic response. In children with chronic phase CML, daily doses can be increased under circumstances similar to those leading to an increase in adult chronic phase disease, from 260 mg/m2/day to 340 mg/m2/day, as clinically indicated.
Dosage of Gleevec should be increased by at least 50%, and clinical response should be carefully monitored, in patients receiving Gleevec with a potent CYP3A4 inducer such as rifampin or phenytoin.
For daily dosing of 800 mg and above, dosing should be accomplished using the 400-mg tablet to reduce exposure to iron.
Dose Adjustment for Hepatotoxicity and Other Non -Hematologic Adverse Reactions
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.
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 or 600 mg to 400 mg). In children, daily doses can be reduced under the same circumstances from 260 mg/m2/day to 200 mg/m2/day or from 340 mg/m2/day to 260 mg/m2/day, respectively.
Dose Adjustment for Hematologic Adverse Reactions
Dose reduction or treatment interruptions for severe neutropenia and thrombocytopenia are recommended as indicated in Table 11.
Table 11 Dose Adjustments for Neutropenia and Thrombocytopenia Chronic Phase CML
(starting dose 400mg1)
| ANC <1.0 x 109/L
and/or
Platelets <50 x 109/L | 1. | Stop Gleevec until ANC ≥1.5 x 109/L and platelets ≥75 x 109/L |
or GIST
(starting dose either
400 mg or 600 mg) | | 2. | Resume treatment with Gleevec at the original starting dose of 400 mg1 or 600 mg |
| | 3. | 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 dose (300 mg2 if starting dose was 400 mg1, 400 mg if starting dose was 600 mg) |
Accelerated Phase
CML and Blast Crisis
(starting dose 600 mg) | 3ANC <0.5 x 109/L
and/or
Platelets <10 x 109/L | 1. | Check if cytopenia is related to leukemia (marrow aspirate or biopsy) |
| | 2. | If cytopenia is unrelated to leukemia, reduce dose of Gleevec to 400 mg |
| | 3. | If cytopenia persists 2 weeks, reduce further to 300 mg |
| | 4. | If cytopenia persists 4 weeks and is still unrelated to leukemia, stop Gleevec until ANC ≥1 x 109/L and platelets ≥20 x 109/L and then resume treatment at 300 mg |
1 or 260 mg/m2 in children
2 or 200 mg/m2 in children
3occurring after at least 1 month of treatment
|
