• Newly diagnosed Philadelphia positive (Ph+) chronic myeloid leukemia (CML).
• CML in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha treatment.
• Kit (CD117) positive metastatic/unresectable malignant GI stromal tumors.
• Adjuvant treatment following resection of Kit (CD117) positive GI stromal tumors.
• Pediatric patients with Ph+ CML after failure of bone marrow transplant or resistance to interferon-alpha.
• Adult patients with relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL).
• Newly diagnosed Ph+ ALL (in combination with chemotherapy).
• Myelodysplastic/myeloproliferative disease associated with platelet-derived growth factor receptor gene rearrangements.
• Aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown.
• Hypereosinophilic syndrome and/or chronic eosinophilic leukemia.
• Unresectable, recurrent, or metastatic dermatofibrosarcoma protuberans.

Contraindicated in:

• Hypersensitivity
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Hepatic impairment (dose ↓ recommended if bilirubin >3 x upper limit of normal (ULN) or AST/ALT >5 x ULN)
• Cardiac disease (severe HF and left ventricular dysfunction may occur)
• Renal impairment, diabetes, hypertension, HF (↑ risk of nephrotoxicity)
• Women of reproductive potential
• Pedi: Children <1 yr (safety and effectiveness not established)
• Geri: ↑risk of edema in older adults.

CV: edema, HF.

Derm: petechiae, pruritus, rash, DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS).

EENT: epistaxis, nasopharyngitis, blurred vision.

Endo: ↓growth (in children), hypothyroidism.

GI: abdominal pain, anorexia, constipation, diarrhea, dyspepsia, nausea, vomiting, HEPATOTOXICITY.

GU: nephrotoxicity.

Hemat: BLEEDING, NEUTROPENIA, THROMBOCYTOPENIA.

Metab: ↑weight.

MS: arthralgia, muscle cramps, myalgia, pain.

Neuro: fatigue, headache, weakness, dizziness, somnolence.

Resp: cough, dyspnea, pneumonia.
Misc: fever, night sweats, TUMOR LYSIS SYNDROME.

Drug-Drug:

• Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, or voriconazole, may ↑ levels and risk of toxicity.
• Strong CYP3A4 inducers, including dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, and phenobarbital, may ↓ levels and effectiveness; if used concurrently, ↑ imatinib dose by 50%.
• May ↑ levels and risk of toxicity of benzodiazepines, simvastatin, and calcium channel blockers.

Drug-Food:

• Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

(Generic available)

• Tablets: 100 mg; 400 mg;

Chronic Myeloid Leukemia

• PO (Adults): Chronic phase: 400 mg once daily, may be ↑ to 600 mg once daily; Accelerated phase or blast crisis: 600 mg once daily; may be ↑ to 800 mg/day given as 400 mg twice daily based on response and circumstances.
• PO (Children): Newly diagnosed Ph+ CML: 340 mg/m² once daily (not to exceed 600 mg); CML recurrence after failure of bone marrow transplant or resistance to interferon-alpha: 260 mg/m² once daily.

Gastrointestinal Stromal Tumors

• PO (Adults): Metastatic or unresectable: 400 mg once daily; may be ↑ to 400 mg twice daily if well tolerated and response insufficient; Adjuvant treatment after resection: 400 mg once daily.

Ph+ Acute Lymphoblastic Leukemia

• PO (Adults): 600 mg once daily.
• PO (Children): 340 mg/m² once daily (not to exceed 600 mg).

Myelodysplastic/Myeloproliferative Diseases

• PO (Adults): 400 mg once daily.

Aggressive Systemic Mastocytosis

• PO (Adults): 400 mg once daily. Patients with eosinophilia: 100 mg once daily; ↑ to 400 mg once daily if well tolerated and response insufficient.

Hypereosinophilic Syndrome and/or Chronic Eosinophilic Leukemia

• PO (Adults): 400 mg once daily. For patients with FIP1L1–PDGFRa fusion kinase: 100 mg once daily; ↑ to 400 mg once daily if well tolerated and response insufficient.

Dermatofibrosarcoma Protuberans

• PO (Adults): 400 mg twice daily.

Gleevec

• Inhibits kinases, which may be produced by malignant cell lines.

• Inhibits production of malignant cell lines with decreased proliferation of leukemic cells in CML, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, and ALL and malignant cells in GI stromal tumor, myelodysplastic/myeloproliferative disease, aggressive systemic mastocytosis, and dermatofibrosarcoma protuberans.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

Absorption: Well absorbed (98%) following oral administration.

Distribution: Unknown.

Protein Binding: 95%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme to N-demethyl imatinib, which is as active as imatinib. Excreted mostly in feces as metabolites. 5% excreted unchanged in urine.

Half-life: Imatinib: 18 hr; N-desmethyl imatinib: 40 hr.

(plasma concentrations of imatinib)

• Explain purpose of imatinib to patient. Instruct patient to take imatinib as directed. If a dose is missed, take next dose at regular scheduled time. Do not double doses.
• Advise patient to avoid grapefruit and grapefruit juice during therapy.
• May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Inform patient of possibility of edema and fluid retention. Advise patient to notify health care professional if unexpected rapid weight gain occurs.
• Advise patient to notify health care professional if signs and symptoms of liver failure (jaundice, anorexia, bleeding or bruising) or DRESS occur.
• Advise female patient of reproductive potential to use effective contraception during and for at least 14 days after last dose of imatinib. Advise patient to notify health care professional if pregnancy is planned or suspected; avoid breastfeeding for at least 1 mo after last dose of imatinib.

i-MAT-i-nib