Imachron

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. Adults 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/ c-Kit mutational status unknown; hypereosinophilic syndrome (HES) &/or chronic eosinophilic leukemia (CEL); Kit+ (CD117) unresectable &/or metastatic malignant GI stromal tumors (GIST); unresectable, recurrent &/or metastatic dermatofibrosarcoma protuberan (DFSP). Adjuvant treatment of adults following resection of Kit+ GIST.

400 or 600 mg doses should be administered once daily; 800 mg daily dose should be administered as 400 mg bid, in morning & evening. Adult Chronic phase CML 400 mg daily, may be increased to 600 or 800 mg. CML in accelerated phase or blast crisis 600 mg daily, may be increased to a max of 800 mg daily. Ph+ ALL 600 mg daily. MDS/MPD 400 mg daily. SM w/o D816V KIT mutation or mutational status unknown or not responding satisfactorily to other therapies 400 mg daily. SM associated w/ eosinophilia, a clonal hematological disease related to the fusion kinase FIP1L1-PDGFR-α Initially 100 mg daily, may be increased to 400 mg. HES/CEL 400 mg daily. HES/CEL w/ demonstrated FIP1L1-PDGFR-α fusion kinase Initially 100 mg daily, may be increased to 400 mg. Unresectable &/or metastatic, malignant GIST 400 mg daily, may be increased to 600 or 800 mg. Adjuvant treatment following resection of GIST 400 mg daily. Min treatment duration: 36 mth. DFSP 800 mg daily. Childn Chronic & advanced phase CML & Ph+ ALL 340 mg/m² daily; not to exceed total dose of 600 mg daily. Treatment can be given as once daily dose in CML & Ph+ ALL. In CML, alternatively daily dose may be split into 2 administrations (1 in morning & 1 in evening). Patient w/ mild, moderate or severe liver dysfunction Min recommended dose of 400 mg daily, can be reduced if not tolerated. Patient w/ renal dysfunction or on dialysis Min recommended dose of 400 mg daily as starting dose. Dose may be reduced if not tolerated, or increased for lack of efficacy.

Should be taken with food: Take w/ large glass of water to minimize risk of GI disturbances. Patient unable to swallow: Tab may be dispersed in glass of water or apple juice. Required number of tab should be placed in appropriate vol of beverage (approx 50 mL for 100 mg tab, 200 mL for 400 mg tab) & stirred w/ a spoon. Susp should be administered immediately after complete disintegration of tab.

Hypersensitivity.

Perform routine monitoring of response to therapy in Ph+ CML patients. Monitor patients for GI symptoms at the start of & during therapy. Consider discontinuation when patient develops GI hemorrhage. Reports of hypothyroidism in thyroidectomy patients undergoing levothyroxine replacement during treatment; occurrences of severe fluid retention; tumor lysis syndrome. Closely monitor TSH levels. Correct clinically significant dehydration & treat high uric acid levels prior to initiation of treatment. Carefully monitor patients w/ cardiac disease, risk factors for cardiac failure or history of renal failure; evaluate & treat any patient w/ signs or symptoms consistent w/ cardiac or renal failure. Risk of hepatitis B reactivation in patients who are chronic carriers of the virus. Test for hepatitis B infection before initiating treatment. Perform regular CBC & monitoring of liver function (transaminases, bilirubin, alkaline phosphatase). Concomitant use w/ rifampicin or other strong CYP3A4 inducers, ketoconazole or other strong CYP3A4 inhibitors, CYP3A4 substrates w/ narrow therapeutic window (eg, cyclosporin or pimozide) or CYP2C9 substrates w/ narrow therapeutic window (eg, warfarin & other coumarin derivatives). Caution when driving a car or operating machinery; may experience undesirable effects (eg, dizziness, blurred vision or somnolence) during treatment. Carefully monitor peripheral blood counts & liver enzymes in patients w/ mild, moderate or severe hepatic dysfunction. Monitor hepatic function when combined w/ chemotherapy regimens also known to be associated w/ hepatic dysfunction. Patients w/ renal dysfunction or on dialysis. Human studies on male patients receiving imatinib mesylate & its effect on male fertility & spermatogenesis have not been performed. Should be used during pregnancy only if the expected benefit outweighs the potential risk to the fetus. Women taking Imachron should not breast-feed. No experience w/ use in childn <2 yr w/ CML & childn <1 yr w/ PH+ ALL. Very limited to no experience in childn in other indications. Reports of growth retardation in childn & pre-adolescents; close monitoring of growth is recommended.

Neutropenia, thrombocytopenia, anemia; headache; nausea, diarrhea, vomiting, dyspepsia, abdominal pain; periorbital edema, dermatitis/eczema/rash; muscle spasm & cramps, musculo-skeletal 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, GERD, 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.

Significantly reduced exposure w/ CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb or Hypericum perforatum, also known as St. John's Wort). Decreased metabolism & increased conc w/ CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, clarithromycin). Increased mean C_max & AUC of simvastatin (CYP3A4 substrate). Caution when co-administering 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). Prothrombin time prolongation was observed w/ warfarin.

Targeted Cancer Therapy

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

Rx