Imachron Dosage/Direction for Use

Therapy should be initiated by a physician experienced in the treatment of patients with hematological malignancies and malignant sarcomas, as appropriate.
The prescribed dose should be administered orally with a meal and a large glass of water to minimize the risk of gastrointestinal disturbances. Doses of 400 mg or 600 mg should be administered once daily, whereas a daily dose of 800 mg should be administered as 400 mg twice a day, in the morning and in the evening.
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 patients (e.g. children) unable to swallow the capsules, their content may be diluted in a glass of still water or apple juice. Since studies in animals have shown reproductive toxicity, and the potential risk for the human fetus is unknown, women of child-bearing potential, who open capsules should be advised to handle contents with caution and avoid skin-eye contact or inhalation (see Fertility, Pregnancy and Lactation). Hands should be washed immediately after handling open capsules.
Treatment should be continued as long as the patient continues to benefit.
Monitoring of response to imatinib mesylate (Imachron) therapy in Ph+ CML patients should be performed routinely and when therapy is modified, to identify suboptimal response, loss of response to therapy, poor patient compliance, or possible drug-drug interaction. Results of monitoring should guide appropriate CML management.
General target population: Dosage in CML: The recommended dosage of imatinib mesylate (Imachron) is 400 mg/day for adult patients in chronic phase CML and 600 mg/day for patients in accelerated phase or blast crisis.
Dose increase from 400 mg to 600 mg or 800 mg in patients with chronic phase disease, or from 600 mg to a maximum of 800 mg daily in 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 hematological response after at least 3 months of treatment; failure to achieve a cytogenetic response after 12 months of treatment; or loss of a previously achieved hematological and/or cytogenetic response.
Dosage in Ph+ ALL: The recommended dose of imatinib mesylate (Imachron) is 600 mg/day for adult patients with Ph+ ALL.
Dosage in MDS/MPD: The recommended dose of imatinib mesylate (Imachron) is 400 mg/day for adult patients with MDS/MPD.
Dosage in SM: The recommended dose of imatinib mesylate (Imachron) is 400 mg/day for adult patients with SM without the D816V KIT mutation or mutational status unknown or not responding satisfactorily to other therapies.
For patients with SM associated with eosinophilia, a clonal hematological disease related to the fusion kinase FIP1L1-PDGFR-alpha, a starting dose of 100 mg/day is recommended. A dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.
Dosage in HES/CEL: The recommended dose of imatinib mesylate (Imachron) is 400 mg/day for adult patients with HES/CEL.
For HES/CEL patients with demonstrated FIP1L1-PDGFR-alpha fusion kinase, a starting dose of 100 mg/day is recommended. A dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.
Dosage in GIST: The recommended dose of imatinib mesylate (Imachron) is 400 mg/day for adult patients with unresectable and/or metastatic, malignant GIST. A dose increase from 400 mg to 600 mg or 800 mg for patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy. The recommended dose of imatinib mesylate (Imachron) is 400 mg/day for the adjuvant treatment of adult patients following resection of GIST. The recommended minimum treatment duration is 36 months.
In the adjuvant setting the optimal treatment duration with imatinib mesylate (Imachron) is not known.
Dosage in DFSP: The recommended dose of imatinib mesylate (Imachron) is 800 mg/day for adult patients with DFSP.
Dose adjustments for adverse drug reactions: Non-hematological adverse drug reactions: If a severe non-hematological adverse drug reaction develops with imatinib mesylate (Imachron) use, treatment must 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, imatinib mesylate (Imachron) should be withheld until bilirubin levels have returned to a <1.5 x IULN and transaminase levels to <2.5 x IULN. Treatment with imatinib mesylate (Imachron) may then be continued at a reduced daily dose. In adults the dose should be reduced from 400 to 300 mg, or from 600 to 400 mg, or from 800 mg to 600 mg, and in children from 340 to 260 mg/m²/day.
Hematological adverse drug reactions: Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia are recommended as indicated in the table as follows. (See Table 12.)

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Special populations: Children: There is no experience with the use of imatinib mesylate (Imachron) in children with CML below 2 years of age and with Ph+ALL below 1 year of age. There is very limited to no experience with the use of imatinib mesylate (Imachron) in children in other indications.
Dosing in children should be on the basis of body surface area (mg/m²). The dose of 340 mg/m² daily is recommended for children with chronic phase and advanced phase CML and Ph+ALL (not to exceed the total dose of 600 mg daily). Treatment can be given as a once daily dose in CML and Ph+ALL. In CML, alternatively the daily dose may be split into two administrations - one in the morning and one in the evening (see Pharmacology: Pharmacodynamics under Actions).
Hepatic insufficiency: Imatinib is mainly metabolized by the liver. Patients with mild, moderate or severe liver dysfunction should be given the minimum recommended dose of 400 mg daily. The dose can be reduced if not tolerated (see Precautions, Adverse Reactions and Pharmacology: Pharmacodynamics under Actions).
Renal insufficiency: Imatinib and its metabolites are not significantly excreted via the kidney. Patients with renal dysfunction or on dialysis could be given the minimum recommended dose of 400 mg daily as starting dose (see Pharmacology: Pharmacodynamics under Actions). However, in these patients caution is recommended. The dose can be reduced if not tolerated. If tolerated, the dose can be increased for lack of efficacy (see Precautions).
Elderly patient: No significant age related pharmacokinetic differences have been observed in adult patients in clinical trials which included over 20% of patients age 65 and older. No specific dose recommendation is necessary in the elderly.