PracticeUpdate: Haematology & Oncology

† FAST Median time to first MR 4.5 reached 1.3 years faster than imatinib (p<0.0001) 1,4

† DEEP The only TKI to get >50% of patients to MR 4.5 by 5 years vs 31% with imatinib (p<0.0001) 1,2

† PROTECTIVE No patient who achieved MR 4.5 progressed to AP/BC (on core treatment; p-value not reported) 1,3

(e.g. chloroquine, methadone, halofantrine, clarithromycin, haloperidol, moxifloxacin, bepridil, pimozide); anti-arrhythmic medicines (e.g. amiodarone, disopyramide, procainamide, quinidine, sotalol); CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, itraconazole, voriconazole, telithromycin); CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine, phenobarbital or St. John’s wort); may be used concurrently with esomeprazole or other proton pump inhibitors and warfarin; exposure to midazolam; drugs affecting P-glycoprotein; avoid grapefruit juice and foods known to inhibit CYP3A4. In concurrent use: the H2 blocker (e.g. famotidine) may be administered approximately 10 hours before and approximately 2 hours after TASIGNA dose, antacids (e.g. aluminum hydroxide, magnesium hydroxide, simethicone) may be administered approximately 2 hours before or approximately 2 hours after TASIGNA dose. Nilotinib is a moderate CYP3A4 inhibitor. As a result, the systemic exposure of other drugs primarily metabolized by CYP3A4 (e.g. certain HMG-CoA reductase inhibitors) may be increased when co-administered with nilotinib. Appropriate monitoring and dose adjustment may be necessary for drugs that are CYP3A4 substrates and have a narrow therapeutic index (including but not limited to alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, astemizole, terfenadine, cisapride, quinidine, pimozide, sirolimus and tacrolimus) when co-administered with nilotinib. Due to possible occurrence of tumour lysis syndrome, correction of clinically significant dehydration and treatment of high uric acid levels are recommended prior to administration. Side effects: Very common: headache, nausea, constipation, diarrhoea, vomiting, rash, pruritus, alopecia, myalgia, arthralgia, fatigue, upper abdominal pain, myelosuppression (thrombocytopenia, neutropenia), hypophosphataemia (including blood phosphorus decreased), hyperbilirubinaemia (including blood bilirubin increased), alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, lipoprotein cholesterol (including low density and high density) increased, total cholesterol increased, blood triglycerides increased. Common: decreased appetite, abdominal pain, muscle spasms, bone pain, pain in extremity, asthenia, oedema peripheral, folliculitis, upper respiratory tract infection (including pharyngitis, nasopharyngitis, rhinitis), skin papilloma, leukopenia, eosinophilia, febrile neutropenia, pancytopenia, lymphopenia, anaemia, electrolyte imbalance (including hyperkalaemia, hypokalaemia, hyponatraemia, hypocalcaemia, hypercalcaemia, hyperphosphataemia, hypomagnesaemia), hyperglycaemia, diabetes mellitus, hypercholesterolaemia, hyperlipidaemia, hypertriglyceridemia, insomnia, depression, anxiety, dizziness, peripheral neuropathy, hypoaesthenia, paraesthesia, eye haemorrhage, periorbital oedema, eye pruritus, conjunctivitis, dry eye (including xerophthalmia), vertigo, angina pectoris, arrhythmia (including atrioventricular block, cardiac flutter, extrasystoles, atrial fibrillation, tachycardia, bradycardia), palpitations, electrocardiogram QT prolonged, flushing, hypertension, dyspnoea, dyspnoea exertional, epistaxis, cough, dysphonia, abdominal discomfort, dyspepsia, dysgeusia, flatulence, abdominal distension, pancreatitis, hepatic function abnormal, night sweats, hyperhidrosis, dry skin, eczema, urticaria, erythema, dermatitis (including allergic, exfoliative and acneiform), contusion, acne, musculoskeletal chest pain, musculoskeletal pain, back pain, neck pain, flank pain, muscular weakness, blood creatine kinase (CK) increased, pollakiuria, pyrexia, chest pain (including non-cardiac chest pain), pain, chest discomfort, malaise, haemoglobin decreased, blood amylase increased, gamma-glutamyltransferase increased, blood creatinine phosphokinase increased, blood alkaline phosphatase increased, blood insulin increased, weight decreased, weight increased, globulins decreased. (See full Product Information). Based on approved Tasigna Product Information dated 15 April 2016. For the most up to date Product Information go to http://www.novartis.com.au/products_healthcare.html Tas150416m.doc *Please note changes in Product Information. References: 1. Hochhaus A et al. Leukemia. 2016;30:1044–54. 2. Cortes J et al. J Clin Oncol 2016;34:2333–40. 3. Kantarjian HM et al. Lancet Oncol 2011;12:841–51. 4. Hughes TP et al. Efficacy and safety of nilotinib versus imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase: 6-year follow-up of ENESTnd. Poster presentation at the 20th Annual European Association Congress; June 11–14, 2015; Vienna, Austria.

Novartis Pharmaceuticals Australia Pty Limited ABN 18 004 244 160. 54 Waterloo Road, Macquarie Park NSW 2113. Ph (02) 9805 3555. For medical enquiries please contact 1800 671 203 or medinfo.phauno@novartis.com. Tasigna ® is a Registered Trademark of Novartis Pharmaceuticals Pty Limited. AU-0722. NOT0023. Date of preparation: January 2017.