Gastrointestinal Stromal Tumours Knowledge Centre

Systemic Therapy

Imatinib - Management of Adverse Events

Although Glivec is generally well tolerated, several common hematologic and nonhematologic adverse events may occur and need to be monitored and managed. Occasionally, dose reduction or brief dose interruption may be necessary.1

Hematologic adverse events

Dose reduction or treatment interruption for severe neutropenia and thrombocytopenia is recommended (Table 1).1

Nonhematologic adverse events

If a severe nonhematologic adverse reaction develops with Glivec 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. Edemas may be managed with diuretics, with other supportive measures, or by reducing the dose of Glivec.

Fluid retention can usually be managed by withholding Glivec temporarily and with diuretics and other appropriate supportive care measures.1

Table 1. Dose Adjustments for Neutropenia and Thrombocytopenia1
Chronic-phase CML and
GIST (starting dose 400
mg)*
ANC <1.0 × 109/L or
platelets <50 × 109/L
  1. Stop Glivec® until ANC ≥1.5 × 109/L and
    platelets ≥75 × 109/L
  2. Resume treatment with Glivec at previous
    dose (ie, before severe adverse reaction)
  3. In the event of recurrence of ANC <1.0 ×
    109/L or platelets <50 × 109/L, repeat step
    1 and resume Glivec at reduced dose of
    300 mg†
Accelerated-phase CML
and blast crisis (starting
dose 600 mg)‡
ANC <0.5 × 109/L§ or
platelets <10 × 109/L
  1. Check whether cytopenia is related to
    leukemia (marrow aspirate or biopsy)
  2. If cytopenia is unrelated to leukemia,
    reduce dose of Glivec to 400 mg*
  3. If cytopenia persists for 2 weeks, reduce
    further to 300 mg†
  4. If cytopenia persists for 4 weeks and is
    still unrelated to leukemia, stop Glivec
    until ANC ≥1 × 109/L and platelets ≥20 ×
    109/L, then resume treatment at 300 mg†

*Or 260 mg/m2 in children.
Or 200 mg/m2 in children.
Or 340 mg/m2 in children.
§ Occurring after at least 1 month of treatment. ANC, absolute neutrophil count; CML, chronic myeloid leukemia; GIST, gastrointestinal stromal tumor.

Liver toxicity

If elevations in bilirubin >3× institutional upper limit of normal (IULN) or if liver transaminases >5× IULN occur, Glivec should be withheld until bilirubin levels have returned to <1.5× IULN and transaminase levels to <2.5× IULN. Treatment with Glivec may then be continued at a reduced daily dose. In adults, the dose should be reduced from 400 mg to 300 mg or from 600 mg to 400 mg; in children, the dose should be reduced from 260 mg to 200 mg/m2/d or from 340 mg to 260 mg/m2/d.

References:

1. Glivec summary of product characteristics [SMPC]. Basel, Switzerland: Novartis Pharma AG; 2006.

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