livec to 260 mg/m2.
3. If cytopenia persists for 2 weeks, reduce further to 200 mg/m2.
4. If cytopenia persists for 4 weeks and is still unrelated to leukaemia, stop Glivec until ANC 1 x 109/l and platelets 20 x 109/l, then reume treatment at 200 mg/m2.
DFSP
(at dose 800 mg)
ANC < 1.0 x 109/l
and/or
platelets < 50 x 109/l
1. Stop Glivec until ANC 1.5 x 109/l and platelets 75 x 109/l.
2. Resume treatment with Glivec at 600 mg.
3. In the event of recurrence of ANC < 1.0 x 109/l and/or platelets < 50 x 109/l, repeat step 1 and resume Glivec at reduced dose of 400 mg.
ANC = absolute neutrophil count
a occurring after at least 1 month of treatment
Paediatric use: There is no experience in children with CML below 2 years of age (see section 5.1). There is limited experience in children with Ph+ ALL and very limited experience in children with MDS/MPD and DFSP. There is no experience in children or adolescents with GIST and HES/CEL.
Hepatic insufficiency: Imatinib is mainly metabolised through 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 sections 4.4, 4.8 and 5.2).
Liver dysfunction classification:
Liver dysfunction
Liver function tests
Mild
Total bilirubin: = 1.5 ULN
AST: >ULN (can be normal or <ULN if total bilirubin is >ULN)
Moderate
Total bilirubin: >1.5–3.0 ULN
AST: any
Severe
Total bilirubin: >3–10 ULN
AST: any
ULN = upper limit of normal for the institution
AST = aspartate aminotransferase
Renal insufficiency: Since the renal clearance of imatinib is negligible, a decrease in free imatinib clearance is not expected in patients with renal insufficiency. Patients with mild or moderate renal dysfunction (creatinine clearance = 20–59 ml/min) should be given the minimum recommended dose of 400 mg daily as starting dose. Although very limited information is available, patients with severe renal dysfunction (creatinine clearance = < 20 ml/min) or on dialysis could also start at the same dose of 400 mg. However, in these patients caution is recommended. The dose can be reduced if not tolerated, or increased for lack of efficacy (see sections 4.4 and 5.2).
Elderly patients: Imatinib pharmacokinetics have not been specifically studied in the 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 the elderly.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
When Glivec is co-administered with other medicinal products, there is a potential for drug interactions (see section 4.5).
Concomitant use of imatinib and medicinal products that induce CYP3A4 (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or Hypericum perforatum, also known as St. John's Wort) may significantly reduce exposure to Glivec, potentially increasing the risk of therapeutic failure. Therefore, concomitant use of strong CYP3A4 inducers and imatinib should be avoided (see section 4.5).
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