Imatinib Mesylate (3 brand names, 3 dosage forms, 1 route)
Available dosage forms: TABLET, CAPSULE, SOLUTION.
Routes of administration: ORAL.
Brand Names
- GLEEVEC
- IMATINIB MESYLATE
- IMKELDI
Contraindications
None.
Adverse Reactions
The following serious adverse reactions are described elsewhere in the labeling: • Fluid Retention and Edema [see Warnings and Precautions ( 5.1)] • Hematologic Toxicity [see Warnings and Precautions ( 5.2)] • Congestive Heart Failure and Left Ventricular Dysfunction [see Warnings and Precautions ( 5.3)] • Hepatotoxicity [see Warnings and Precautions ( 5.4)] • Hemorrhage [see Warnings and Precautions ( 5.5)] • Gastrointestinal Disorders [see Warnings and Precautions ( 5.6)] • Hypereosinophilic Cardiac Toxicity [see Warnings and Precautions ( 5.7)] • Dermatologic Toxicities [see Warnings and Precautions ( 5.8)] • Hypothyroidism [see Warnings and Precautions ( 5.9)] • Growth Retardation in Children and Adolescents [see Warnings and Precautions ( 5.11)] • Tumor Lysis Syndrome [see Warnings and Precautions ( 5.12)] • Impairments Related to Driving and Using Machinery [see Warnings and Precautions ( 5.13)] • Renal Toxicity [see Warnings and Precautions ( 5.14)]
Mechanism of Action
Imatinib mesylate is a proteintyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Imatinib inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Imatinib inhibits colony formation in assays using ex vivoperipheral blood and bone marrow samples from CML patients. In vivo, imatinib inhibits tumor growth of BCR-ABL transfected murine myeloid cells as well as BCR-ABL positive leukemia lines derived from CML patients in blast crisis. Imatinib is also an inhibitor of the receptor tyrosine kinases for plateletderived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in GIST cells, which express an activating c-Kit mutation.
Overdosage
Experience with doses greater than 800 mg is limited. Isolated cases of imatinib mesylate overdose have been reported. In the event of overdosage, observe the patient and give appropriate supportive treatment. Adult Overdose 1,200 to 1,600 mg (duration varying between 1 to 10 days):Nausea, vomiting, diarrhea, rash erythema, edema, swelling, fatigue, muscle spasms, thrombocytopenia, pancytopenia, abdominal pain, headache, decreased appetite. 1,800 to 3,200 mg (as high as 3,200 mg daily for 6 days):Weakness, myalgia, increased CPK, increased bilirubin, GI pain. 6,400 mg (single dose):One case in the literature reported one patient who experienced nausea, vomiting, abdominal pain, pyrexia, facial swelling, neutrophil count decreased, increase transaminases. 8 to 10 g (single dose):Vomiting and GI pain have been reported. A patient with myeloid blast crisis experienced Grade 1 elevations of serum creatinine, Grade 2 ascites and elevated liver transaminase levels, and Grade 3 elevations of bilirubin after inadvertently taking 1,200 mg of imatinib mesylate tablets daily for 6 days. Therapy was temporarily interrupted and complete reversal of all abnormalities occurred within 1 week. Treatment was resumed at a dose of 400 mg daily without recurrence of adverse reactions. Another patient developed severe muscle cramps after taking 1,600 mg of imatinib mesylate tablets daily for 6 days. Complete resolution of muscle cramps occurred following interruption of therapy and treatment was subsequently resumed. Another patient that was prescribed 400 mg daily, took 800 mg of imatinib mesylate tablets on Day 1 and 1,200 mg on Day 2. Therapy was interrupted, no adverse reactions occurred and the patient resumed therapy. Pediatric Overdose One 3 year old male exposed to a single dose of 400 mg experienced vomiting, diarrhea, and anorexia; and another 3 year old male exposed to a single dose of 980 mg experienced decreased white blood cell (WBC) count and diarrhea.