Glivec

Imatinib mesilate

Adult & ped patients: Treatment of newly diagnosed Philadelphia chromosome +ve (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the 1st-line of treatment; Ph+ CML in chronic phase after failure of interferon-α therapy, or in accelerated phase or blast crisis; newly diagnosed Philadelphia chromosome +ve acute lymphoblastic leukaemia (Ph+ ALL) integrated w/ chemotherapy. Adult patients: Treatment of relapsed or refractory Ph+ ALL as monotherapy; myelodysplastic/myeloproliferative diseases (MDS/MPD) associated w/ platelet-derived growth factor receptor (PDGFR) gene re-arrangements; advanced hypereosinophilic syndrome (HES) &/or chronic eosinophilic leukaemia (CEL) w/ FIP1L1-PDGFRα rearrangement. Treatment of Kit (CD117) +ve unresectable &/or metastatic malignant GI stromal tumours (GIST). Adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit +ve GIST. Treatment of unresectable dermatofibrosarcoma protuberans (DFSP) & recurrent &/or metastatic DFSP in patients not eligible for surgery.

Adult Chronic phase CML 400 mg/day, may be increased to 600 or 800 mg. Accelerated phase or blast crisis CML 600 mg/day, may be increased to 800 mg (given as 400 mg bd, 1 in the morning & 1 in the evening). Ph+ ALL 600 mg/day. Relapsed/refractory Ph+ ALL 600 mg/day. MDS/MPD 400 mg/day. HES/CEL 100 mg/day, may be increased to 400 mg. Unresectable &/or metastatic, malignant GIST 400 mg/day, may be increased to 600 or 800 mg. Adjuvant treatment following resection of GIST 400 mg/day. DFSP 800 mg/day. Childn Chronic or advanced phase CML 340 mg/m² daily, may be increased to 570 mg/m² daily. Max total dose: 800 mg. Ph+ ALL 340 mg/m² daily. Max total dose: 600 mg. Patient w/ mild, moderate or severe liver dysfunction 400 mg daily, may be reduced if not tolerated. Patient w/ renal dysfunction or on dialysis 400 mg daily, may be reduced if not tolerated.

Should be taken with food: Take w/ meals to minimize GI irritation. For patients w/ swallowing difficulties, open cap & dilute contents in a glass of water/apple juice.

Hypersensitivity.

Reports of hypothyroidism in thyroidectomy patients undergoing l-thyroxine replacement; liver injury; severe fluid retention; GI haemorrhage; thrombotic microangiopathy. Risk of tumour lysis syndrome; HBV reactivation; phototoxicity. Carefully monitor peripheral blood counts & liver enzymes in patients w/ hepatic dysfunction. Carefully monitor patients w/ cardiac disease or risk factors for cardiac failure or history of renal failure. Perform CBC & monitor liver function regularly during treatment. Long-term treatment may be associated w/ clinically significant decline in renal function. Evaluate renal function prior to start of therapy, & closely monitor during therapy. Caution w/ concomitant use of PIs, azole antifungals, certain macrolides, CYP3A4 substrates w/ narrow therapeutic window, warfarin & other coumarin derivatives. Avoid concomitant use of strong CYP3A4 inducers. Possible dizziness, blurred vision or somnolence; advise caution when driving a car or operating machinery. Women of childbearing potential must use effective contraception during treatment for at least 15 days after stopping treatment. Not to be used during pregnancy unless clearly necessary. Do not breast-feed during treatment & for at least 15 days after stopping treatment. Reports of growth retardation occurring in childn & pre-adolescents. Close monitoring of growth in childn is recommended. No experience in childn <2 yr w/ CML & childn <1 yr w/ Ph+ ALL. Safety & efficacy have not been established in childn <18 yr w/ MDS/MPD, DFSP, GIST & HES/CEL.

Neutropenia, thrombocytopenia, anaemia; headache; nausea, diarrhoea, vomiting, dyspepsia, abdominal pain; periorbital oedema, dermatitis/eczema/rash; muscle spasm & cramps, musculoskeletal pain (eg, myalgia, arthralgia, bone pain); fluid retention & oedema, fatigue; increased wt. Pancytopenia, febrile neutropenia; anorexia; insomnia; dizziness, paraesthesia, taste disturbance, hypoaesthesia; eyelid oedema, increased lacrimation, conjunctival haemorrhage, conjunctivitis, dry eye, blurred vision; flushing, haemorrhage; dyspnoea, epistaxis, cough; flatulence, abdominal distension, gastro-oesophageal reflux, constipation, dry mouth, gastritis; increased hepatic enzymes; pruritus, face oedema, dry skin, erythema, alopecia, night sweats, photosensitivity reaction; joint swelling; weakness, pyrexia, anasarca, chills, rigors; decreased wt.

Increased plasma conc w/ CYP3A4 inhibitors (eg, indinavir, lopinavir/ritonavir, saquinavir, telaprevir, nelfinavir, boceprevir; ketoconazole, itraconazole, posaconazole, voriconazole; erythromycin, clarithromycin, telithromycin). Decreased plasma conc w/ CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb, fosphenytoin, St. John's wort). Increased C_max & AUC of simvastatin, CYP3A4 substrates w/ narrow therapeutic window (eg, cyclosporine, pimozide, tacrolimus, sirolimus, ergotamine, diergotamine, fentanyl, alfentanil, terfenadine, bortezomib, docetaxel & quinidine), other CYP3A4 substrates (eg, triazolo-benzodiazepines, dihydropyridine Ca channel blockers, certain HMG-CoA reductase inhibitors). Increased risk of bleeding w/ coumarin derivatives eg, warfarin. Increased plasma conc of CYP2D6 substrates w/ narrow therapeutic window (eg, metoprolol). Inhibited paracetamol O-glucuronidation. Decreased plasma exposure to l-thyroxine. Increased hepatotoxicity w/ L-asparaginase.

Targeted Cancer Therapy

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

P₁S₁S₃