Glivec

Adult & paed patients: Treatment of newly diagnosed Philadelphia chromosome +ve (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as 1st line of treatment; Ph+ CML in chronic phase after failure of interferon-α therapy, or in accelerated phase or blast crisis; newly diagnosed Ph+ acute lymphoblastic leukaemia (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 rearrangements; advanced hypereosinophilic syndrome (HES) &/or chronic eosinophilic leukaemia (CEL) w/ FIP1L1-PDGFRα rearrangement; Kit (CD117) +ve unresectable &/or metastatic malignant GI stromal tumours (GIST); unresectable dermatofibrosarcoma protuberans (DFSP), & recurrent &/or metastatic DFSP not eligible for surgery. Adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117) +ve GIST.

Administer 400-mg or 600-mg doses once daily, & 800-mg daily dose as 400 mg bd (in the morning & in the evening). Adult Chronic phase CML 400 mg/day, may be increased to 600 mg or 800 mg. Accelerated phase or blast crisis CML 600 mg/day, may be increased to max of 800 mg. Newly diagnosed or 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 mg 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; w/ renal dysfunction or on dialysis 400 mg daily, may be reduced if not tolerated.

Should be taken with food: Administer w/ meal & water to minimise risk of GI irritation. If unable to swallow tab: May disperse tab in still water or apple juice; place required number of tab in appropriate vol of beverage (approx 50 mL for 100-mg tab) & stir; administer susp immediately after complete disintegration of tab.

Hypersensitivity.

Risk of hypothyroidism in thyroidectomy patients undergoing levothyroxine replacement; liver injury, including hepatic failure & necrosis; severe fluid retention; cardiac adverse events; GI haemorrhage; tumour lysis syndrome; HBV reactivation; phototoxicity; thrombotic microangiopathy. Perform CBC & monitor liver function regularly during therapy. 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. Test for HBV infection before initiating treatment. Closely monitor HBV carriers for signs & symptoms of active HBV infection throughout therapy & for several mth following termination of therapy. Caution when taking w/ PIs, azole antifungals, certain macrolides, CYP3A4 substrates w/ narrow therapeutic window, or warfarin & other coumarin derivatives. Avoid concomitant use w/ strong CYP3A4 inducers. Caution when driving a car or operating machinery due to possible dizziness, blurred vision or somnolence during treatment. Women of childbearing potential must use effective contraception during treatment & for at least 15 days after stopping treatment. Should not be used during pregnancy unless clearly necessary. Potential risk to foetus if used during pregnancy. Do not breast-feed during treatment & for at least 15 days after stopping treatment. Reports of growth retardation in childn & pre-adolescents. Closely monitor growth in childn under treatment. 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 including 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, PIs (eg, indinavir, lopinavir/ritonavir, saquinavir, telaprevir, nelfinavir, boceprevir), azole antifungals (eg, ketoconazole, itraconazole, posaconazole, voriconazole), certain macrolides (eg, erythromycin, clarithromycin, telithromycin). Decreased plasma conc w/ CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb, fosphenytoin, primidone, St. John's wort). Increased plasma conc of CYP3A4 substrates w/ narrow therapeutic window (eg, simvastatin, 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); CYP2D6 substrates w/ narrow therapeutic window (eg, metoprolol). Increased risk of bleeding w/ coumarin derivatives eg, warfarin. Inhibited O-glucuronidation of paracetamol. Decreased plasma exposure to levothyroxine. 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.

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