Tykodas

Dasatinib

Adults w/ newly diagnosed Philadelphia chromosome +ve (Ph+) chronic myelogenous leukaemia (CML) in chronic phase (Ph+ CML-CP); chronic, accelerated or blast phase CML w/ resistance or intolerance to prior therapy including imatinib; Ph+ acute lymphoblastic leukaemia (ALL) & lymphoid blast CML w/ resistance or intolerance to prior therapy. Paed patients w/ newly diagnosed Ph+ CML-CP or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib; newly diagnosed Ph+ ALL in combination w/ chemotherapy.

Adult Chronic phase CML Initially 100 mg once daily. May increase dose to 140 mg in patient who did not achieve haematologic or cytogenetic response at recommended starting dose. Accelerated, myeloid or lymphoid blast phase (advanced phase) CML or Ph+ ALL Initially 140 mg once daily. May increase dose to 180 mg in patient who did not achieve haematologic or cytogenetic response at recommended starting dose. Paed Ph+CML-CP or Ph+ ALL Patient weighing at least 45 kg 100 mg daily, 30 to <45 kg 70 mg daily, 20 to <30 kg 60 mg daily, 10 to <20 kg 40 mg daily. Patient w/ Ph+CML-CP who did not achieve haematologic, cytogenetic & molecular response at recommended time points w/ starting dose of 80 mg Max: 120 mg daily, starting dose of 70 mg Max: 90 mg daily, starting dose of 60 mg Max: 70 mg daily, starting dose of 40 mg Max: 50 mg daily. Concomitant use of strong CYP3A4 inhibitor Patient taking 140 mg tab daily Decrease dose to 40 mg daily, taking 100 mg & 70 mg tab daily Decrease dose to 20 mg daily.

May be taken with or without food: Swallow whole, do not crush/cut/chew.

Hypersensitivity.

Interrupt therapy during evaluation of patients who develop dyspnoea & fatigue after treatment initiation for pleural effusion, pulmonary oedema, anaemia, or lung infiltration; if signs or symptoms of cardiac adverse reactions develop. Permanently discontinue treatment if pulmonary arterial HTN is confirmed. Discontinue if lab or clinical findings associated w/ thrombotic microangiopathy occur. Evaluate patients who develop symptoms suggestive of pleural effusion (eg, dyspnoea or dry cough) by chest X-ray; for signs & symptoms of underlying cardiopulmonary disease prior to initiating therapy. Monitor patients w/ risk factors (eg, HTN, hyperlipidaemia, diabetes) or history of cardiac disease (eg, prior percutaneous coronary intervention, documented CAD) for chest pain, shortness of breath, & diaphoresis; HBV carriers who require treatment for signs & symptoms of active HBV infection throughout therapy & for several mth following termination of therapy. Correct hypokalaemia or hypomagnesaemia prior to therapy. Perform test to patients for HBV infection before initiating treatment. Anaemia, neutropaenia & thrombocytopaenia; bleeding/haemorrhage. Fluid retention. Potential to prolong cardiac ventricular repolarisation (QT interval). CHF/cardiac dysfunction, pericardial effusion, arrhythmias, palpitations, QT prolongation & MI. Patients taking medicinal products that inhibit platelet function or anticoagulants; who have or may develop QTc prolongation; w/ hypokalaemia or hypomagnesaemia, congenital long QT syndrome, those taking anti-arrhythmic medicinal products or other medicinal products leading to QT prolongation, & cumulative high dose anthracycline therapy; w/ uncontrolled or significant CV disease. Perform CBC wkly for the 1st 2 mth, then mthly thereafter in adults w/ advanced phase CML or Ph+ ALL; every 2 wk for 12 wk, then every 3 mth thereafter in adults & paed patients w/ chronic phase CML; prior to start of each block of chemotherapy in paed patients w/ Ph+ ALL; every 2 days until recovery during consolidation blocks of chemotherapy; echocardiography at treatment initiation in every patient w/ cardiac disease & risk factors for cardiac or pulmonary disease. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Not recommended in concomitant use w/ potent CYP3A4 inhibitors eg, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice; H₂ antagonist (eg, famotidine), PPI (eg, omeprazole). Concomitant use w/ CYP3A4 inducers [dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb or herbal prep containing Hypericum perforatum (St. John's Wort)], & substrates of narrow therapeutic index eg, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, dihydroergotamine). Administer Al-/Mg hydroxide up to, or 2 hr following administration of treatment. May affect ability to drive & use machines. Hepatic & renal impairment. Sexually active men & women of childbearing potential should use effective methods of contraception during treatment. Male patients should be counselled on semen deposition. Congenital malformations including neural tube defects. Not to be used during pregnancy. Discontinue lactation during treatment. Not recommended to use tab in paed patients weighing <10 kg. Monitor bone growth & development in paed patients. Childn <1 yr. Monitor elderly ≥65 yr for pleural effusion, dyspnoea, cough, pericardial effusion & CHF.

Infection (including bacterial, viral, fungal, non-specified); myelosuppression (including anaemia, neutropaenia, thrombocytopaenia); headache; haemorrhage; pleural effusion, dyspnoea; diarrhoea, vomiting, nausea, abdominal pain; skin rash; musculoskeletal pain; peripheral & face oedema, fatigue, pyrexia. Pneumonia (including bacterial, viral, & fungal), URTI/upper resp tract inflammation, herpes virus (including cytomegalovirus) & enterocolitis infection, sepsis (including uncommon cases w/ fatal outcomes); febrile neutropaenia; appetite disturbances, hyperuricaemia; depression, insomnia; neuropathy (including peripheral neuropathy), dizziness, dysgeusia, somnolence; visual disorder (including visual disturbance, blurred vision, & reduced visual acuity), dry eye; tinnitus; CHF/cardiac dysfunction, pericardial effusion, arrhythmia (including tachycardia), palpitations; HTN, flushing; pulmonary oedema & HTN, lung infiltration, pneumonitis, cough; GI bleeding, colitis (including neutropaenic colitis), gastritis, mucosal inflammation (including mucositis/stomatitis), dyspepsia, abdominal distension, constipation, oral soft tissue disorder; alopecia, dermatitis (including eczema), pruritus, acne, dry skin, urticaria, hyperhidrosis; arthralgia, myalgia, muscular weakness, musculoskeletal stiffness, muscle spasm; asthenia, pain, chest pain, generalised oedema, chills; decreased/increased wt; contusion.

Increased exposure w/ potent CYP3A4 inhibitors eg, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice. Decreased AUC w/ rifampicin. Increased metabolism & decreased plasma conc w/ CYP3A4 inducers eg, dexamethasone, phenytoin, carbamazepine, phenobarb or herbal prep containing Hypericum perforatum (St. John's Wort). Reduced exposure w/ H₂ antagonists or PPIs (eg, famotidine & omeprazole). Reduced AUC & C_max w/ Al-/Mg hydroxide antacids. Increased exposure to CYP3A4 substrates w/ narrow therapeutic index eg, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, dihydroergotamine). Increased AUC & C_max exposure to simvastatin.

Targeted Cancer Therapy

L01EA02 - dasatinib ; Belongs to the class of BCR-ABL tyrosine kinase inhibitors. Used in the treatment of cancer.

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