Iminox

Imatinib mesilate

Newly diagnosed chronic myeloid leukaemia (CML) & CML in blast crisis, accelerated phase or in chronic phase after failure of interferon-α therapy. Newly diagnosed Philadelphia chromosome +ve acute lymphoblastic leukaemia (Ph+ ALL) integrated w/ chemotherapy. Adults: Unresectable &/or metastatic malignant GI stromal tumours (GIST). Adjuvant treatment following GIST resection. Relapsed or refractory Ph+ ALL as monotherapy. Myelodysplastic/-proliferative diseases (MDS/MPD) associated w/ platelet-derived growth factor receptor (PDGFR) gene rearrangements. Hypereosinophilic syndrome (HES) &/or chronic eosinophilic leukaemia (CEL) w/ F1P1L1-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.

Adult Chronic phase CML, GIST 400 mg daily, may be increased to 600 or 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; MDS/MPD, ASM, HES/CEL 400 mg daily. Ph+ ALL 600 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 impairment, renal insufficiency, on dialysis Min recommended dose: 400 mg daily.

Should be taken with food.

Hypersensitivity.

Fluid retention; patients w/ cardiac dysfunction, history of cardiac disease; GI haemorrhage; tumour lysis syndrome; thrombotic microangiopathy. Perform CBC & monitor liver function regularly. Closely monitor TSH levels in thyroidectomy patients. Perform HBV screening before initiation of treatment. Avoid exposure to direct sunlight. Long-term use. Avoid use w/ strong CYP3A4 inducers. Concomitant use w/ PIs, azole antifungals, certain macrolides, CYP3A4 substrates w/ narrow therapeutic window, warfarin & other coumarin derivatives. May affect ability to drive & use machines. Hepatotoxicity; renal failure, severe 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; 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 mean C_max & AUC of simvastatin. 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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