Glivec

Imatinib mesylate

Adult & ped patients w/ newly diagnosed Philadelphia chromosome +ve chronic myeloid leukemia (Ph+ CML); Ph+ CML in blast crisis, accelerated phase or in chronic phase after failure of interferon-α therapy; newly diagnosed Philadelphia chromosome +ve acute lymphoblastic leukemia (Ph+ ALL) integrated w/ chemotherapy. Adult patients w/ relapsed or refractory Ph+ ALL as monotherapy; myelodysplastic/myeloproliferative diseases (MDS/MPD) associated w/ platelet-derived growth factor receptor (PDGFR) gene re-arrangements; systemic mastocytosis (SM) w/o D816V c-Kit mutation or w/ unknown c-Kit mutational status; hypereosinophilic syndrome (HES) &/or chronic eosinophilic leukemia (CEL); Kit+ (CD117) unresectable &/or metastatic malignant gastrointestinal stromal tumors (GIST); unresectable, recurrent &/or metastatic dermatofibrosarcoma protuberans (DFSP). Adjuvant treatment of adult patients following resection of Kit+ GIST.

Adult CML Chronic phase: 400 mg daily, may be increased to 600 or 800 mg daily in absence of severe adverse drug reaction & severe non-leukemia-related neutropenia or thrombocytopenia. Accelerated phase or blast crisis: 600 mg daily, may be increased to max of 800 mg daily in absence of severe adverse drug reaction & severe non-leukemia-related neutropenia or thrombocytopenia. Ph+ ALL 600 mg daily. MDS/MPD 400 mg daily. SM w/o D816V KIT mutation or w/ unknown mutational status, HES/CEL 400 mg daily. SM associated w/ eosinophilia, HES/CEL w/ demonstrated FIP1L1-PDGFR-α fusion kinase Initially 100 mg daily, may be increased to 400 mg daily in absence of adverse drug reaction if assessment demonstrates insufficient response to therapy. Unresectable &/or metastatic malignant GIST 400 mg daily, may be increased to 600 or 800 mg in absence of adverse drug reaction if assessment demonstrates insufficient response to therapy. Adjuvant treatment following GIST resection 400 mg daily. Min treatment duration: 36 mth. DFSP 800 mg daily. Renal impairment or on dialysis, mild, moderate or severe hepatic impairment Min recommended dose: 400 mg daily as starting dose. Ped patient <18 yr CML (chronic & advanced phase), Ph+ ALL 340 mg/m² once daily. Not to exceed total dose of 600 mg daily. In CML, alternatively may split daily dose into 2 administration: 1 in morning & 1 in evening.

Should be taken with food: Take w/ large amount of water.

Hypersensitivity.

Severe fluid retention. Tumor lysis syndrome. Hepatitis B reactivation in patients who are chronic carriers of HBV. Closely monitor thyroidectomy patients undergoing levothyroxine replacement for TSH levels; patients w/ cardiac disease, risk factors for cardiac failure or history of renal failure; patients for GI symptoms at start of & during therapy. Regularly perform CBC & monitor liver function (transaminases, bilirubin, alkaline phosphatase) during therapy. Concomitant use w/ rifampicin or other strong CYP3A4 inducers, ketoconazole or other strong CYP3A4 inhibitors, CYP3A4 (eg, cyclosporin or pimozide) or CYP2C9 (eg, warfarin & other coumarin derivatives) substrates w/ narrow therapeutic window. Caution when driving a car or operating machinery. Monitor peripheral blood counts & liver enzymes in mild, moderate or severe hepatic impairment; hepatic function in combination w/ chemotherapy regimens associated w/ hepatic dysfunction. Evaluate renal function prior to the start of therapy & closely monitor during therapy. Females of reproductive potential should use effective contraception during & for at least 15 days after treatment. Pregnancy. Not recommended during lactation & for at least 15 days after treatment. Closely monitor growth of ped patients <18 yr under treatment. Ped patients w/ CML <2 yr & ALL <1 yr.

Neutropenia, thrombocytopenia, anemia; headache; nausea, diarrhea, vomiting, dyspepsia, abdominal pain; periorbital edema, dermatitis/eczema/rash; muscle spasm & cramps, musculoskeletal pain including myalgia, arthralgia, bone pain; fluid retention & edema, fatigue; increased wt. Pancytopenia, febrile neutropenia; anorexia; insomnia; dizziness, paresthesia, taste disturbance, hypoaesthesia; eyelid edema, increased lacrimation, conjunctival hemorrhage, conjunctivitis, dry eye, blurred vision; flushing, hemorrhage; dyspnea, epistaxis, cough; flatulence, abdominal distension, gastroesophageal reflux, constipation, dry mouth, gastritis; increased hepatic enzymes; pruritus, face edema, dry skin, erythema, alopecia, night sweats, photosensitivity reaction; joint swelling; weakness, pyrexia, anasarca, chills, rigors; decreased wt.

Exposure may be reduced w/ CYP3A4 inducers eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb or St. John's wort. Increased oral-dose clearance w/ rifampicin; enzyme-inducing anti-epileptic drugs eg, carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarb & primidone. Decreased AUC w/ St. John's wort. Decreased metabolism & increased conc w/ CYP3A4 inhibitors eg, ketoconazole, itraconazole, erythromycin, clarithromycin. Increased exposure w/ ketoconazole. Increased mean C_max & AUC of simvastatin. Concomitant use w/ CYP3A4 substrates w/ narrow therapeutic window eg, cyclosporin or pimozide. May increase plasma conc of other CYP3A4 metabolized drugs eg, triazolo-benzodiazepines, dihydropyridine Ca channel blockers, certain HMG-CoA reductase inhibitors (ie, statins). PT prolongation w/ warfarin.

Targeted Cancer Therapy

L01EA01 - imatinib ; Belongs to the class of BCR-ABL tyrosine kinase inhibitors. Used in the treatment of cancer.

Rx