Dasatinib Sandoz

Dasatinib

Adults w/ newly diagnosed chronic myeloid leukemia (CML) in chronic phase; chronic, accelerated, or myeloid or lymphoid blast phase CML, & Philadelphia chromosome +ve acute lymphoblastic leukemia (Ph+ ALL) w/ resistance or intolerance to prior therapy including imatinib.

Adult Chronic phase CML Initially 100 mg once daily. May increase dose to 140 mg once daily in patients who did not achieve haematologic or cytogenetic response at recommended starting dose. Accelerated, myeloid or lymphoid blast phase (advanced phase) CML & Ph+ ALL Initially 140 mg once daily. May increase dose to 180 mg once daily in patients who did not achieve haematologic or cytogenetic response at recommended starting dose. Concomitant use w/ strong CYP3A4 inhibitors Patient taking dasatinib 140 mg daily Decrease dose to 40 mg daily, 100 mg or 70 mg daily Decrease dose to 20 mg daily.

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

Hypersensitivity.

Permanently discontinue treatment if pulmonary arterial HTN (PAH) is confirmed. Discontinue treatment if labor clinical findings associated w/ thrombotic microangiopathy occur. Interrupt therapy if clinical signs or symptoms of cardiac dysfunction develops. Anaemia, neutropaenia & thrombocytopaenia; bleeding. Fluid retention; pre-capillary PAH. CHF/cardiac dysfunction, pericardial effusion, arrhythmias, palpitations, QT prolongation & MI. Reactivation of hepatitis B in patients who are chronic carriers resulting to acute hepatic failure or fulminant hepatitis. Patients who are taking medicinal products that inhibit platelet function or anticoagulants; may develop QTc prolongation eg, those w/ hypokalaemia or hypomagnesaemia, congenital long QT syndrome, taking anti-arrhythmics or other QT prolonging medicinal products, & cumulative high dose anthracycline therapy; w/ uncontrolled or significant CV disease. Lactose-intolerant patients. Perform CBC wkly for the 1st 2 mth, then mthly thereafter in adults w/ advanced phase CML or Ph+ ALL treated w/ monotherapy; every 2 wk for 12 wk, then every 3 mth thereafter in adults w/ chronic phase CML; echocardiography at treatment initiation in patient w/ symptoms of cardiac disease & risk factors for cardiac or pulmonary disease. 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. Closely monitor patients ≥65 yr for pleural effusion, dyspnoea, cough, pericardial effusion & CHF; carriers of HBV 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. Carefully monitor patients w/ risk factors (eg, HTN, hyperlipidaemia, diabetes) or history of cardiac disease (eg, prior percutaneous coronary intervention, documented CAD) for clinical signs or symptoms consistent w/ cardiac dysfunction eg, chest pain, shortness of breath, & diaphoresis. Test patients for HBV infection before initiating treatment. Not recommended in concomitant use w/ potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice); H₂ antagonists & PPIs. Concomitant use w/ CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb or herbal prep containing Hypericum perforatum [St. John's Wort]); CYP3A4 substrates of narrow therapeutic index eg, astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, dihydroergotamine). Administer Al-/Mg hydroxide products 2 hr prior to or following dasatinib. May affect ability to drive & use machines. Hepatic impairment. Sexually active men & women of childbearing potential should use effective methods of contraception during treatment. Male patients should be counselled about possible effects on fertility & consideration of semen deposition. Congenital malformations including neural tube defects during pregnancy. Not to be used during pregnancy. Discontinue lactation during treatment.

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 oedema, fatigue, pyrexia, face oedema. Pneumonia (including bacterial, viral, & fungal), upper resp tract infection/inflammation, herpes virus infection (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, & visual acuity reduced), 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. SJS.

Increased exposure of CYP3A4 inhibitors eg, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice. 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 & PPIs eg, famotidine & omeprazole. Reduced AUC & C_max w/ omeprazole; 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 w/ simvastatin. Concomitant use w/ CYP2C8 substrates eg, glitazones.

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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