Imatinib

• Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML): Oral:

Chronic phase: 400 mg once daily; may be increased to 600 mg daily, if tolerated, for disease progression, lack of hematologic response after 3 months, lack of cytogenetic response after 6 to 12 months, or loss of previous hematologic or cytogenetic response. An increase to 800 mg daily has been used

• Accelerated phase or blast crisis: 600 mg once daily; may be increased to 800 mg daily (400 mg twice daily), if tolerated, for disease progression, lack of hematologic response after 3 months, lack of cytogenetic response after 6 to 12 months, or loss of previous hematologic or cytogenetic response

• Ph+ acute lymphoblastic leukemia (ALL) (relapsed or refractory): Oral: 600 mg once daily

• Gastrointestinal stromal tumors (GIST) (adjuvant treatment following complete resection): Oral: 400 mg once daily; recommended treatment duration: 3 years

• GIST (unresectable and/or metastatic malignant): Oral: 400 mg once daily; may be increased up to 800 mg daily (400 mg twice daily), if tolerated, for disease progression. Note: Significant improvement (progression-free survival, objective response rate) was demonstrated in patients with KIT exon 9 mutation with 800 mg (versus 400 mg), although overall survival (OS) was not impacted. The higher dose did not demonstrate a difference in time to progression or OS patients with Kit exon 11 mutation or wild-type status

• Aggressive systemic mastocytosis (ASM) associated with eosinophilia: Oral: Initiate at 100 mg once daily; if assessments demonstrate insufficient response, increase from 100 mg to 400 mg/day in the absence of adverse reactions.

• ASM without D816V c-Kit mutation or c-Kit mutation status unknown: Oral: 400 mg once daily

Dermatofibrosarcoma protuberans (DFSP): Oral: 400 mg twice daily

• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL): Oral: 400 mg once daily

• HES/CEL with FIP1L1-PDGFRα fusion kinase: Oral: Initiate at 100 mg once daily; if assessments demonstrate insufficient response, increase from 100 mg to 400 mg/day in the absence of adverse reactions.

• Myelodysplastic/myeloproliferative disease (MDS/MPD) with PDGF receptor gene rearrangements: Oral: 400 mg once daily

• Chordoma, progressive, advanced, or metastatic expressing PDGFRB and/or PDGFB (off-label use): Oral: 400 mg twice daily

• Desmoid tumors, unresectable and/or progressive (off-label use): Oral: 300 mg twice daily (BSA ≥1.5 m²), 200 mg twice daily (BSA 1 to 1.49 m²), 100 mg twice daily (BSA <1 m²) (Chugh 2010) or 400 mg once daily; may increase to 400 mg twice daily if progressive disease on 400 mg daily (Penel 2011)

Melanoma, advanced or metastatic with C-KIT mutation (off-label use): Oral: 400 mg twice daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

• Note: Imatinib is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting

• Acute lymphoblastic leukemia (ALL), Philadelphia chromosome-positive (Ph+); newly diagnosed: Children and Adolescents: Oral: 340 mg/m²/day administered once daily; in combination with intensive chemotherapy (Schultz 2014); maximum daily dose: 600 mg/day; treatment may be continued until disease progression or unacceptable toxicity

• Chronic myeloid leukemia (CML), Philadelphia chromosome-positive (Ph+); chronic phase, newly diagnosed: Children and Adolescents: Oral: 340 mg/m²/day administered once daily or in 2 divided doses; maximum daily dose: 600 mg/day. Treatment may be continued until disease progression or unacceptable toxicity. The optimal duration of therapy for CML in complete remission is not yet determined. Discontinuing CML treatment is not recommended unless part of a clinical trial

• Dosing adjustment with concomitant strong CYP3A4 inducers: Children and Adolescents: Avoid concomitant use of strong CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin); if concomitant use cannot be avoided, increase imatinib dose by at least 50% with careful monitoring.

• Dosing adjustment for nonhematologic adverse reactions: Children and Adolescents: Withhold treatment until toxicity resolves; may resume if appropriate (depending on initial severity of adverse event)

• Dosing adjustment for hematologic adverse reactions: Children and Adolescents:

ALL Ph+ (newly diagnosed): Hematologic toxicity requiring dosage adjustments was not observed in the study. No major toxicities were observed with imatinib at 340 mg/m²/day in combination with intensive chemotherapy

• CML Ph+ (chronic phase): If ANC <1 x 10⁹/L and/or platelets <50 x 10⁹/L: Withhold until ANC ≥1.5 x 10⁹/L and platelets ≥75 x 10⁹/L; resume treatment at previous dose. For recurrent neutropenia and/or thrombocytopenia, withhold until recovery and reinstitute treatment at a reduced dose as follows: If initial dose 340 mg/m²/day, reduce dose to 260 mg/m²/day.