Iminox Dosage/Direction for Use

Dosage Regimen and Administration: Therapy should be initiated by a physician experienced in the treatment of patients with haematological 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).
Treatment should be continued as long as the patient continues to benefit.
Monitoring of response to Imatinib 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 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-leukaemia-related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time); failure to achieve a satisfactory haematological 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 haematological and/or cytogenetic response.
See Special populations: Paediatric patients (below 18 years) as follows.
Dosage in Ph+ ALL: The recommended dose of Imatinib is 600 mg/day for adult patients with Ph+ ALL.
See Special populations: Paediatric patients (below 18 years) as follows.
Dosage in MDS/MPD: The recommended dose of Imatinib is 400 mg/day for adult patients with MDS/MPD.
Dosage in ASM: The recommended dose of Imatinib is 400 mg/day for adult patients with ASM without the D816V c-KIT mutation or mutational status unknown or not responding satisfactorily to other therapies.
For patients with ASM associated with eosinophilia, a clonal haematological 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 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 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 is 400 mg/day for the adjuvant treatment of adult patients following complete gross resection of GIST. The optimal treatment duration with Imatinib is not known.
Dosage in DFSP: The recommended dose of Imatinib is 800 mg/day for adult patients with DFSP.
Dose adjustments for adverse drug reactions: Non-haematological adverse drug reactions: If a severe non-haematological adverse drug reaction develops with Imatinib 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 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 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 paediatric patients 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 1.)

Click on icon to see table/diagram/image

Special populations: 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. 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.
Hepatic impairment: Imatinib is mainly metabolized by the liver. Patients with mild, moderate or severe liver impairment should be given the minimum recommended dose of 400 mg daily. The dose can be reduced if not tolerated.
Paediatric patients (below 18 years): There is no experience with the use of Imatinib in paediatric patients 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 in paediatric patients in other indications.
Dosing in paediatric patients 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.
Geriatric patients (65 years or above): No significant age-related pharmacokinetic differences have been observed in adult patients which included patients age 65 and older. No specific dose recommendation is necessary in the elderly.
Route of Administration: Oral.