1. Peig Carroll CML Nurse Specialist St. James’s Hospital Dublin

2. Objectives  To review the common side effects of the Tyrosine Kinase Inhibitors (TKI’s) that are currently used in the treatment of CML  To increase awareness of some of the different side effect profiles of each one  To offer practical advice on how to manage the non- haematological side effects

3.  Most patients with Chronic Myeloid Leukaemia will require life long treatment in the form of a Tyrosine Kinase Inhibitor (TKI)  Strict medication adherence is required to achieve and maintain a good response to treatment  Reduction and management of side effects from TKIs is essential for quality of life

4. Dasatinib (Sprycel)  Diarrhoea  Headache  Cough  Skin rash  Fever  Nausea/Indigestion  Fatigue  Muscle pain  Infections Nilotinib (Tasigna)  Diarrhoea  Constipation  Vomiting  Arthralgias (joint aches/pains)  Cough  Rash  Pruritis (itching)  Nausea  Headache  Fatigue Imatinib (Glivec)  Oedema (fluid retention)  Nausea/ indigestion  Muscle cramps  Musculoskeletal pain  Diarrhoea  Rash  Fatigue  Headache  Abdominal pain Common Side Effects

5.  Swelling of eyelids very common with Imatinib  Mild diuretic, reduce salt intake, maintain hydration  Dry Eyes - Lacrilube (lubricating gel) apply at night, Artificial tears, apply anytime  Subconjunctival Haemorrhage (Blood shot eye) Unsightly but not dangerous. Clear-eye drops

6.  More common in the first few weeks of taking TKIs  Reduced by taking Imatinib (Glivec) after a meal, may help to divide dose to twice a day  Nilotinib (Tasigna) on an empty stomach, 2 hours after and 1 hour before food  Dasatinib can be taken with or without food, dose should not be divided  Anti-nausea drugs available if necessary, Metoclopramide, (Maxolon) all 3 TKIs  Take 1 hour before dose

7.  If history of indigestion or heartburn - breath test to check for presence of Helicobacter Pylori infection  If present treat with antibiotics and proton pump inhibitor  Imatinib and Nilotinib, Omeprazole (Losec) or Lansoprazole (Zoton)  Dasatinib - H2 blockers or proton pump inhibitors not recommended. If required should be taken 12 hours apart

8.  Can occur with all 3 TKIs  Topical hydrocortisone creams  Antihistamines particularly if itchy  If rash is severe drug should be held and oral Prednisone given. TKI should be restarted at lower dose and increased on weekly basis to full dose if tolerated  Mild red pimply type rash, low dose antibiotic

9.  Dry Skin - use daily moisturiser  Maintain adequate daily fluid intake  Increased Photo Sensitivity (burn from sun more easily)  Avoid direct sunlight – always wear high factor sun screen and a hat

10.  Leg Cramps – Calcium and Magnesium supplement (CAL-MAG) taken daily  Musculoskeletal pain – Paracetamol in small amounts - no more than 2 grams per day  Ibuprofen non-steroidal anti inflammatory (NSAI) can cause stomach upset/pain  Heat packs -Topical anti-inflammatory gels/creams  Gentle non-weight bearing exercise

11.  Interferes with the person’s ability to carry out ordinary daily activities and it is not relieved by rest or sleep  Reduced activity and exercise causes aches and pains, weakened muscles and fitness  Fatigue can result in avoiding activity  This in turn can cause emotions of Frustration, Anxiety, Sadness, leading to further fatigue

12.  Regular exercise improves energy and mood  Set realistic goals, begin slowly and increase workouts gradually  Get plenty of sleep and try to reduce stress  Cognitive behavioural therapy, Yoga and meditation increase feelings of wellbeing  Eat foods high in energy, keep hydrated

13.  Diarrhoea common with high dose Imatinib  Less common with Nilotinib or Dasatinib  Eat foods like pasta, rice or bread, which are high in carbohydrates  Keep hydrated, maintain fluid intake - 2 liters per day  Anti-diarrhoeal medicine, Loperamide

14.  More common with Nilotinib and Dasatinib  Increase fibre intake, eat more fruit, wholegrain bread and cereal, vegetables  Increase fluid intake  20 – 30 minutes gentle exercise per day  If required stool softners, lactulose and mild laxative, senokot

15.  Pleural effusions [fluid on the lung] appear to be a unique side effect of Dasatinib  Symptoms suggestive of pleural effusion include shortness of breath, dry cough, chest pain  Chest x-rays should be undertaken to confirm diagnosis  To relieve symptoms a low dose diuretic (fluid tablet) should be used.  More severe cases may need fluid drained or prednisolone Pleural Effusion

16.  All TKIs are metabolised (broken down) in the liver and kidneys  Nilotinib (Tasigna) is associated with elevated lipase and bilirubin (pancreatic enzyme used for breaking down fats); hyperglycaemia (increased blood sugar level);  Imatinib (Glivec) is associated with hypophosphataemia, (low phosphate); hypokalemia (low calcium) in a proportion of patients – Calcium supplements sometimes advised  Blood Glucose and Renal Liver Bone tests should be carried out regularly to monitor any changes

17.  Side effects can vary from patient to patient and can be mild to severe regardless of age  Careful consideration should be given to each patient’s medical history when choosing a TKI  Choice of second-line treatment should involve consideration of patients previous side-effect profile  Do not always assume that symptoms are related to side effect of medication. Seek medical advice if symptoms arise suddenly or become severe