Monograph Details
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Neoplasms
> Kinase inhibitors
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GLEEVEC |
| Manufacturer |
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Novartis Pharmaceuticals Corp |
| Legal Classification |
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Rx
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| Pharmacological Class |
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Signal transduction inhibitor. |
| Generic Name |
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Imatinib (as mesylate) 100mg, 400mg; tabs. |
| Indications |
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Philadelphia-chromosome (+) chronic myeloid leukemia (CML): in newly-diagnosed adults and children in chronic phase; in patients in blast crisis, accelerated phase, or chronic phase after failure of interferon-alpha therapy; in children with Ph (+ ) chronic phase CML whose disease recurred after stem cell transplant or who are resistant to interferon alpha. Adults with relapsed or refractory Ph (+) acute lymphoblastic leukemia (ALL). Patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements. Adults with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown. Patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unkown. Adults with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP). Kit (CD117) (+) unresectable and/or metastatic malignant GI stromal tumors (GIST). |
| Children |
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Take with food and water in 1 or 2 divided doses; may disperse tab in water or apple juice and take promptly. <2yrs: not recommended. ≥2yrs: Newly diagnosed Ph+CML: 340mg/m2 per day (max 600mg). Chronic phase CML recurrent after stem cell transplant or resistant to interferon-α therapy: 260mg/m2 per day. If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Hematologic reactions: see literature. Potent CYP3A4 inducers (eg, phenytoin): increase imatinib dose by at least 50%; monitor closely. |
| Adults |
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Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: Chronic phase CML: 400mg once daily. Accelerated phase or blast crisis: 600mg once daily. Relapsed/refractory Ph+ ALL: 600mg once daily. MDS/MPD: 400mg once daily. ASM without D816V c-Kit mutation or status unknown: 400mg once daily. ASM associated with eosinophilia: initially 100mg once daily; may increase to 400mg once daily if insufficient response. HES/CEL: 400mg once daily. HES/CEL w. FIP1L1-PDGFRα fusion kinase: initially 100mg once daily; may increase to 400mg once daily if insufficient response. DFSP: 400mg twice daily. GIST: 400mg or 600mg once daily. If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: initially 300mg once daily. Hematologic reactions: see literature. Potent CYP3A4 inducers (eg, rifampin): increase imatinib dose by at least 50%. |
| Precautions |
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Hepatic or renal impairment. Immunosuppressed. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed. Cardiovascular disease. Elderly. Avoid pregnancy (Cat.D); nursing mothers: not recommended; see literature. |
| Interactions |
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Potentiated by CYP3A4 inhibitors (eg, azole antifungals, macrolides). Antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, phenobarbital, carbamazepine, St. John's wort, rifampin). May potentiate drugs metabolized by CYP3A4 (eg, acetaminophen, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, pimozide, statins), CYP2D6, or CYP2C9 (use heparin instead of warfarin). |
| Adverse Reactions |
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GI disturbances, edema (may be severe), bleeding, muscle cramps, fever, pain, rash (may be severe; eg, erythema multiforme, Stevens-Johnson syndrome), fatigue, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression; rare: severe CHF, left ventricular dysfunction. |
| How Supplied |
100mg—100
400mg—30 |
| Additional Resources |
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• Related Prescribing Note |
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