NEOPAX FILM-COATED TABLET 400MG [SIN17065P]

Product Info

NEOPAX FILM-COATED TABLET 400MG

[SIN17065P]

4.1 Therapeutic indications

Neopax is indicated for the

• treatment of adult and paediatric patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukaemia (Ph+ CML).

• treatment of adult and paediatric patients with Ph+ CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.

• treatment of paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy.

• treatment of adult patients with relapsed or refractory Ph+ ALL as monotherapy.

• treatment of adult patients with Kit+ (CD 117) unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).

• adjuvant treatment of adult patients following complete gross resection of Kit+ GIST.

The effectiveness of imatinib is based on overall haematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ ALL, on objective response rates in unresectable and/or metastatic GIST and on recurrence-free survival in adjuvant GIST. Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating increased survival.

4.2 Posology and method of administration

Posology

Therapy should be initiated by a physician experienced in the treatment of patients with haematological malignancies or GIST, as appropriate.

For doses of 400 mg and above (see dosage recommendation below) a 400 mg tablet (not divisible) is available.
For doses other than 400 mg and 800 mg (see dosage recommendation below) a 100 mg divisible tablet is available.

The prescribed dose should be administered orally with a meal and a large glass of water to minimise 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 film-coated tablets, the tablets may be dispersed in a glass of still 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 in adult patients

The recommended dosage of Neopax 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 prescribed dose should be administered orally, once daily with a meal and a large glass of water.

Dose increases from 400 mg to 600 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. Patients should be monitored closely following dose escalation given the potential for an increased incidence of adverse reactions at higher dosages.

Posology for CML in children
Dosing for children should be on the basis of body surface area (mg/m²). The recommended dose of Neopax for children with newly diagnosed Ph+ CML is 340 mg/m²/day (not to exceed 600mg). Doses of 260 mg/m²/day and 340 mg/m²/day are recommended for children with chronic phase CML and advanced phase CML respectively, after failure of interferon-alpha therapy. However, the total daily dose in children should not exceed adult equivalent doses of 400 mg and 600 mg respectively. Treatment can be given as a once daily dose or alternatively the daily dose may be split into two administrations – one in the morning and one in the evening. The dose recommendation is currently based on a small number of paediatric patients.
There is no experience with the treatment of children below 2 years of age.

Posology for Ph+ ALL in adult patients
The recommended dose of Neopax is 600 mg/day for adult patients with relapsed/refractory Ph+ ALL.

Posology for Ph+ ALL in children
Dosing for children should be on the basis of body surface area (mg/ m²). The recommended dose of Neopax to be given in combination with chemotherapy to children with newly diagnosed Ph+ALL is 340 mg/m²/day (not to exceed 600 mg). Treatment can be given as a once daily dose. The dose recommendation is currently based on a small number of paediatric patients.

Posology for GIST
The recommended dose of Neopax 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.

Treatment with imatinib in GIST patients should be continued until disease progression.

The recommended dose of Neopax is 400 mg/day for the adjuvant treatment of adult patients following resection of GIST. Optimal treatment duration is not yet established. Length of treatment in the clinical trial supporting this indication was 36 months.

Dose adjustment for adverse reactions

Non-haematological adverse reactions
If a severe non-haematological adverse 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 < 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 children from 260 to 200 mg/m²/day or from 340 to 260 mg/m²/day.

Haematological adverse reactions
Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia are recommended as indicated in the table below.

Dose adjustments for neutropenia and thrombocytopenia:

Special populations

Paediatric population
There is no experience in children with CML below 2 years of age and with Ph+ALL below 1 year of age.

Dosing in pediatric patients should be on the basis of body surface are (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 impairment
Imatinib is mainly metabolised through the liver. Patients with mild or moderate liver dysfunction should be given the minimum recommended dose of 400 mg daily, and patients with severe liver dysfunction should start at 300 mg daily. The dose can be reduced if not tolerated (see sections 4.4, 4.8 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Renal impairment
Imatinib and its metabolites are not significantly excreted via the kidney. Patients with renal dysfunction or on dialysis should 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 (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Elderly
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 elderly.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.