Imatinib
Mechanism :
Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). It inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia.
Indication :
- Philadelphia chromosome positive chronic phase CML
- Philadelphia chromosome positive (Ph+) ALL
Contraindications :
Contraindicated in patients with hypersensitivity to imatinib or to any other component.
Dosing :
Above 1 year:
340 mg/m²/day orally; Max: 600 mg/day.
Below 1 year:
Safety and efficacy not established.
Adverse Effect :
Muscle cramps, nausea and vomiting, edema, diarrhea, myalgia, musculoskeletal pain, rash, bone marrow suppression, nasopharyngitis, dyspepsia, cough, abdominal pain.
Interaction :
Ketoconazole, Itraconazole, Erythromycin, Clarithromycin, substances that inhibit the Cytochrome P450 Isoenzyme (CYP3A4) activity: May increase imatinib plasma concentrations.
Inducers of CYP3A4 (e.g., Dexamethasone, Phenytoin, Carbamazepine, Rifampin, Phenobarbital): May decrease imatinib plasma concentrations.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function. |
| <10 | Dose as in normal renal function. |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in normal renal function |
| HD | Unlikely to be dialysed. Dose as in normal renal function |
| HDF/High flux | Unlikely to be dialysed. Dose as in normal renal function |
| CAV/VVHD | Unknown dialysability. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
Mild to moderate hepatic impairment: No adjustment necessary
Severe hepatic impairment: Reduce dose by 25%
Hepatotoxicity during therapy
If elevations of bilirubin >3 times upper limit of normal (ULN) or liver transaminases >5 times ULN: withhold treatment until bilirubin <1.5 times ULN and transaminases <2.5 times ULN. Resume treatment at a reduced dose as follows: If current dose 340 mg/m2/day, reduce dose to 260 mg/m2/day. Maximum daily dose range:300 to 400 mg/day