Trevive Dosage/Direction for Use

Therapy should be initiated by a physician experienced in the treatment of patients with haematological malignancies and malignant sarcomas, as appropriate. For doses of 400 mg and above (see dosage recommendation as follows) a 400 mg tablet (not divisible) is available.
For doses other than 400 mg and 800 mg (see dosage recommendation as follows) a 100 mg divisible tablet is available.
The prescribed dose should be administered orally with a meal and a large glass of water to minimize the risk of gastrointestinal irritations. 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 tablets, the tablets may be dissolved 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.
Posology for CML: The recommended dosage of Imatinib Tablets is 400 mg/day for adult patients in chronic phase CML and 600mg/day for patients in accelerated phase or blast crisis.
Dose increases 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 in patients with 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 use as follows).
Posology for GIST: The recommended dose of Imatinib Tablets is 400 mg/day for adult patients with unresectable and/or metastatic malignant GIST. A dose increases 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 Tablets is 400 mg/day for the adjuvant treatment of adult patients following complete gross resection of GIST. The optimal treatment duration with Imatinib Tablets is not known.
Posology for Ph+ ALL: The recommended dose of Imatinib Tablets is 600 mg/day for adult patients with Ph+ ALL (see Special populations: Paediatric use as follows). Haematological experts in the management of this disease should supervise the therapy throughout all phases of care.
Posology for MDS/MPD: The recommended dose of Imatinib Tablets is 400 mg/day for adult patients with MDS/MPD.
Posology for ASM: The recommended dose of Imatinib Tablets 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.
Posology for HES/CEL: The recommended dose of Imatinib Tablets 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.
Posology for DFSP: The recommended dose of Imatinib Tablets is 800 mg/day for adult patients with DFSP.
Dose adjustment for adverse reactions: Non-haemotological adverse reactions: If a severe non-haematological adverse reaction develops with Imatinib Tablets 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 Tablets should be withheld until bilirubin levels have returned to < 1.5 x IULN and transaminase levels to <2.5 x IULN. Treatment with Imatinib Tablets 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 260mg/m²/day.
Haematological adverse 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: Paediatric use: There is no experience 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 use of Imatinib Tablets 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.
Hepatic insufficiency: Imatinib is mainly metabolised by 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.
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.
Route of Administration: Oral.