Trevive

Imatinib mesylate

Newly diagnosed chronic myeloid leukaemia (CML) & CML in blast crisis, accelerated phase or in chronic phase after failure of interferon-α therapy. Unresectable &/or metastatic malignant GI stromal tumours (GIST). Newly diagnosed Philadelphia chromosome +ve acute lymphoblastic leukaemia (Ph+ ALL) integrated w/ chemotherapy. Relapsed or refractory Ph+ ALL as monotherapy. Myelo-/myeloproliferative diseases (MDS/MPD) associated w/ platelet-derived growth factor receptor (PDGFR) gene rearrangements. Hypereosinophilic syndrome (HES) &/or chronic eosinophilic leukaemia (CEL) w/ FIP1L1-PDGFRα rearrangement. Unresectable, recurrent &/or metastatic dermatofibrosarcoma protuberans (DFSP). Aggressive systemic mastocytosis (ASM) w/o D816V c-Kit mutation or w/ c-Kit mutational status unknown. Adjuvant treatment of adults following GIST resection.

Adult Chronic phase CML, GIST 400 mg daily, may be increased to 600-800 mg daily. Accelerated phase or blast crisis CML 600 mg daily, may be increased to max 800 mg daily. Adjuvant treatment following GIST resection 400 mg daily. Ph+ ALL 600 mg daily. MDS/MPD, ASM, HES/CEL 400 mg daily. ASM w/ eosinophilia, HES/CEL w/ demonstrated FIP1L1-PDGFRα fusion kinase Initially 100 mg daily, may be increased to 400 mg daily. DFSP 800 mg daily. Childn Chronic & advanced phase CML & Ph+ ALL 340 mg/m² daily. Max total dose: Not to exceed 600 mg daily. Hepatic & renal dysfunction, on dialysis Min recommended dose: 400 mg daily.

Should be taken with food: Take w/ meals to minimise GI irritation. For patients w/ difficulty swallowing, dissolve tab completely in a glass of water/apple juice & drink immediately.

Hypersensitivity.

Fluid retention; patients w/ cardiac dysfunction, history of cardiac disease; GI haemorrhage; tumour lysis syndrome. Correct dehydration & uric acid levels prior to initiation. Regularly perform CBC. Closely monitor TSH levels, peripheral blood counts & liver enzymes. Avoid use w/ strong CYP3A4 inducers. Concomitant use w/ rifampicin, azole antifungals, certain macrolides, CYP3A4 substrates w/ narrow therapeutic window, warfarin & other coumarin derivatives. May affect ability to drive & use machines. Hepatic & renal impairment. Women of childbearing potential should use effective contraception. Not to be used during pregnancy & lactation. Childn w/ CML <2 yr; w/ Ph+ALL <1 yr. Growth retardation in childn & pre-adolescents. Elderly.

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, gastrooesophageal 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/ PIs eg, indinavir, lopinavir/ritonavir, ritonavir, saquinavir, telaprevir, nelfinavir, boceprevir; azole antifungals eg, ketoconazole, itraconazole, posaconazole, voriconazole; macrolides eg, erythromycin, clarithromycin, telithromycin. Decreased plasma conc w/ dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb, fosphenytoin, primidone or Hypericum perforatum (St. John's wort). Increased plasma conc of other CYP3A4-metabolised drugs eg, triazolobenzodiazepines, dihydropyridine Ca-channel blockers, certain HMG-CoA reductase inhibitors ie, statins. Increased risk of bleeding w/ coumarin derivatives eg, warfarin. Decreased plasma exposure to levothyroxine. Increased hepatotoxicity w/ L-asparaginase. CYP3A4 substrates w/ narrow therapeutic window eg, cyclosporine, pimozide, tacrolimus, sirolimus, ergotamine, diergotamine, fentanyl, alfentanil, terfenadine, bortezomib, docetaxel, quinidine); CYP2D6 substrates w/ narrow therapeutic window eg, metoprolol; paracetamol; chemotherapy regimens.

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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