Tykinib 100

Imatinib mesilate

Adult & ped patients w/ newly diagnosed Philadelphia chromosome (bcr-abl) +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 w/ 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; unresectable dermatofibrosarcoma protuberans (DFSP), & recurrent &/or metastatic DFSP who are not eligible for surgery.

Adult CML Chronic phase: 400 mg daily. Accelerated phase: 600 mg daily. Blast crisis: 600 mg daily. May increase dose to 600 or 800 mg for chronic phase, or to a max of 800 mg (given as 400 mg bid) for accelerated phase or blast crisis. Treatment duration: Continue treatment until disease progression. Ph+ALL 600 mg daily. Relapsed or refractory Ph+ ALL 600 mg daily, given until disease progression occurs. MDS/MPD 400 mg daily. Treatment duration. Continue treatment until disease progression. HES/CEL 100 mg daily, may increase to 400 mg if response to therapy is insufficient. Continue treatment as long as the patient continues to benefit. DFSP 800 mg daily. Childn CML Chronic & advanced phase: 340 mg/m² once daily or may split daily dose into 2 administrations. May increase dose to 570 mg/m² daily. Max total dose: 800 mg. Ph+ ALL 340 mg/m² daily. Max total dose: 600 mg. Mild, moderate or severe liver dysfunction Min dose of 400 mg daily. May reduce dose if not tolerated. Renal dysfunction or on dialysis Min dose of 400 mg daily. May reduce dose if not tolerated or, if tolerated, may increase dose for lack of efficacy.

Should be taken with food.

Hypersensitivity.

Hypothyroidism in thyroidectomy patients undergoing levothyroxine replacement during treatment; closely monitor TSH levels. Monitor peripheral blood counts & liver enzymes in patients w/ hepatic dysfunction. GIST patients may have hepatic metastases which could lead to hepatic impairment; increased serious hepatic reactions when combined w/ high dose chemotherapy regimens. Occurrences of severe fluid retention & tumour lysis syndrome. Monitor patients w/ cardiac disease, risk factors for cardiac failure or history of renal failure. Perform echocardiogram & determination of serum troponin in patients w/ HES/CEL & MDS/MPD associated w/ high eosinophil levels before initiation of therapy. GI & intra-tumoural haemorrhages in patients w/ unresectable &/or metastatic GIST. Reactivation of hepatitis B in patients who are chronic carriers; test for HBV infection before initiating treatment & monitor for signs & symptoms of active HBV infection throughout therapy & for several mth following termination of therapy. Risk of phototoxicity w/ direct exposure to sunlight. Thrombotic microangiopathy. Regularly perform CBC during therapy; monitor liver function (transaminases, bilirubin, alkaline phosphatase). Co-administration w/ PIs, azole antifungals, certain macrolides, CYP3A4 substrates w/ a narrow therapeutic window (eg, cyclosporine, pimozide, tacrolimus, sirolimus, ergotamine, diergotamine, fentanyl, alfentanil, terfenadine, bortezomib, docetaxel, quinidine) or warfarin & other coumarin derivatives. Avoid concomitant use w/ CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb or St. John's Wort). Renal impairment. Women of childbearing potential should use effective contraception during treatment. Pregnancy. Women should not breastfed during treatment. Growth retardation in childn & pre-adolescents. Childn <2 yr w/ CML & <1 yr w/ Ph+ ALL.

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.

Decreased metabolism & increased conc w/ CYP3A4 inhibitors (eg, PIs eg, indinavir, lopinavir/ritonavir, ritonavir, saquinavir, telaprevir, nelfinavir, boceprevir; azole antifungals including ketoconazole, itraconazole, posaconazole, voriconazole; certain macrolides eg, erythromycin, clarithromycin & telithromycin). Increased exposure w/ ketoconazole. May reduce exposure w/ CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb, fosphenytoin, primidone or St. John's Wort). Decreased C_max & AUC_(0-∞) w/ rifampicin. Decreased plasma AUC w/ enzyme-inducing anti-epileptic medicinal products eg, carbamazepine, oxcarbazepine & phenytoin. Increased mean C_max & AUC of simvastatin. CYP3A4 substrates w/ a narrow therapeutic window (eg, cyclosporine, pimozide, tacrolimus, sirolimus, ergotamine, diergotamine, fentanyl, alfentanil, terfenadine, bortezomib, docetaxel & quinidine). May increase plasma conc of other CYP3A4 metabolised medicinal products (eg, triazolo- benzodiazepines, dihydropyridine Ca channel blockers, certain HMG-CoA reductase inhibitors, ie, statins). Increased risk of bleeding w/ coumarin derivatives eg, warfarin. Increased C_max & AUC of metoprolol. Inhibited paracetamol O-glucuronidation. May decrease plasma exposure to levothyroxine in thyroidectomy patients. 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.

Rx