University College Hospital

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1 University College Hospital Exjade treatment for iron overload North Central London Haemoglobinopathy Network jointly with Whittington Health, Royal Free London and Luton and Dunstable NHS Foundation Trust Joint Red Cell Unit

2 2 If you need a large print, audio or translated copy of the document, please contact us on We will try our best to meet your needs. Contents What is Exjade (deferasirox)? 3 Why is too much iron in the body a bad thing? 3 When can Exjade be a useful treatment? 3 How does Exjade work? 4 How is Exjade taken? 4 Can Exjade be given with other iron chelators? 5 How do you monitor the effectiveness of Exjade? 5 What are the side effects of Exjade? 5 Monitoring for side effects of Exjade 7 Contact details 8 Where can I get more information? 9 Space for notes and questions 10

3 3 What is Exjade (deferasirox)? Deferasirox (also known by the brand name Exjade ) is a type of iron chelator, a medicine used to treat iron overload. It works by binding to iron and removing it from the body. Why is too much iron in the body a bad thing? Too much iron is harmful to the tissues where it accumulates. This occurs mainly in the liver and can cause liver scarring (known as fibrosis), leading to a severe form of liver damage (known as cirrhosis) and eventually liver failure. However, this can take many years to develop as the liver is better equipped to deal with iron overload than other tissues. In transfusion-dependent thalassaemia patients, iron can also deposit in the heart, leading to heart failure. Excess iron can also affect: The glands that control growth, sexual development and fertility Insulin production, causing diabetes The glands that control thyroid hormone Bone formation. When can Exjade be a useful treatment? Exjade has been shown to remove excess iron from the liver and heart, and reduce liver damage. It is commonly used in patients with transfusion-dependant thalassaemia, sickle cell disease or anaemias, when iron builds up because of repeated top-up blood transfusions. Exjade is also licensed for non-transfusion-dependant thalassaemia patients who develop too much iron in the body even without blood transfusions.

4 4 How does Exjade work? Exjade is small enough to be absorbed through the gut and to enter the bloodstream. It binds to iron either in the bloodstream or within tissues, such as the liver or heart. Once iron is bound to Exjade, it is eliminated from the body in the faeces. Very little iron is removed in the urine, so that the urine does not go red as with other chelators (such as Desferal or Ferriprox ) that eliminate iron in the urine. How is Exjade taken? Exjade comes as a tablet to take by mouth. It is usually taken once a day with or after food. Drop one tablet into a glass of water to disperse (it does not dissolve) and mix it well with a wooden or plastic stirrer that does not contain metal. You can also disperse the tablet in a fruit drink or juice as long as it is not too thick (for example, a smoothie or banana juice drink are not suitable). The effective and safe dose depends on how much iron is already in the body, and how rapidly iron is accumulating from blood transfusions or from absorption in the diet. For example, if you are receiving quite a lot of blood regularly, a high dose of Exjade will usually be needed to keep pace with the iron loading rate. This does not apply if the blood is given as an automated exchange transfusion, which is the case for some sickle cell disease patients. If the iron has accumulated in the past but the current rate of iron loading is slow, a smaller dose will be effective in reducing the amount of iron in the body. It is also very important to understand that as the amount of iron falls with Exjade treatment, the dose of Exjade may need to be reduced. Doses often need to decrease when ferritin falls below 1000µg/L or if the fall in ferritin is too rapid.

5 5 If the Exjade doses remain high when the levels of iron fall, there is a risk of over-chelation. This could increase the risk of side effects from Exjade (please see below for information about side effects). To prevent this, we will monitor you carefully and adjust the doses accordingly. Can Exjade be given with other iron chelators? Combining Exjade with another chelator may be useful when iron control is inadequate during the treatment with Exjade alone. The clinical experience of combining Exjade with other chelators has been fairly limited so far, but some carefully conducted trials have shown that this approach can be useful and well tolerated. How do you monitor the effectiveness of Exjade? As with other chelators, monitoring of the serum ferritin levels and trend (whether the ferritin levels are going up or down) is the best way to check how effective the Exjade treatment is. MRI (magnetic resonance imaging) scan of the liver and heart can also be used for dose adjustment and to check the amount of iron loading. MRI scans are typically performed about once a year. What are the side effects of Exjade? As with any treatment, there are side effects associated with Exjade. These are more likely to occur if the dose is too high for the level of iron overload or the rate of iron loading. Fortunately, the side effects of Exjade have been looked at in very large clinical trials so that the frequency at which these occur are well known.

6 6 The most common side effects include: Gut discomforts (occurring in about 15 out of 100 patients), such as mild abdominal discomfort or pain, nausea, vomiting, diarrhea and constipation lasting about eight days. These are typically mild and non-persistent, and rarely require dose adjustment or stopping treatment. If they persist, please talk to the doctor prescribing the treatment. Rarely, stomach ulcers have occurred, particularly when the Exjade was given with medicines that irritate the stomach, such as some painkillers. Skin rashes.(occurring in about 11 out of 100 patients). These usually manifest as red and itchy (sometimes raised) bumps, and may occur all over the body or can be limited to the palms and feet. The rash typically develops within two weeks of starting treatment and responds well to temporary dose reduction. Sometimes steroids can be given for the rash and very rarely Exjade treatment needs to be stopped permanently. Raised markers of kidney function. Kidney function is monitored with a blood test that checks the levels of serum creatinine. Serum creatinine increases by about 30% in about 30 out of 100 patients and is not usually a cause for concern. Rarely, the creatinine can increase by more than this and if this continues, Exjade may need to be stopped temporarily or given at a lower dose. Abnormalities in liver function. This usually improves as the iron levels are reduced. Less than one out of 100 patients may have an increase in liver enzymes greater than twice the upper limit of normal, which may require a break in treatment. Your liver function will also be closely monitored during treatment. Unlike Ferriprox, Exjade is not linked to joint pains and does not affect the white cell count, so weekly blood count monitoring is not required.

7 7 Unlike Desferal, Exjade over-treatment is not typically associated with hearing or eyesight problems, although all patients are still monitored as a precaution. Rarely, cataracts have been reported with both Desferal and Exjade. Also unlike Desferal, the use of Exjade at current recommended doses does not seem to affect growth in children. In clinical trials, patients using Exjade reported better satisfaction, convenience of use and quality of life compared to patients using Desferal. Monitoring for side effects of Exjade It is important that we monitor you regularly to avoid under or overtreatment. There are some specific monitoring tests that you will need to have. They are performed more often when the treatment is first started or if the dose is changed (particularly when the dose is increased). The monitoring tests include: Kidney function tests these include blood tests to check the levels of serum creatinine, and urine tests to measure protein-tocreatinine ratio. Serum creatinine will be checked as part of regular blood tests done before each transfusion, and urine tests will be performed at the same time. Liver function tests these should be done at the time of the cross match, usually every week for four weeks when treatment is first started or dose increased. Eye and ear tests ear tests are done every one or two years. Eye tests are performed as part of thalassaemia or sickle cell follow-up, not specifically because you take Exjade. For more information about chelation therapy, please see our leaflet, Treatment options for iron overload.

8 8 Contact details Haematology advice line (office hours, adults and children): Adult haematology advice line (out of hours): Paediatric helpline (out of hours): nurse in charge ward T11 south ext or Apheresis: Address: The Joint Red Cell Unit Department of Haematology 3rd Fl West, 250 Euston Rd London NW1 2PG Website: Haematoloy consultants: Professor John Porter Dr Sara Trompeter Dr Perla Eleftheriou Dr Bernard Davis Dr Farrukh Shah Specialist nurses: Bernadette Hylton (adults) Nancy Huntley (apheresis) Catherine Mkandawire (children)

9 9 Where can I get more information? Manufacturer s leaflet: Website: Thalassaemia International Federation: Website: about-hb-disorders/about%20thal_chapt%204_iron. pdf The Sickle Cell Society Tel: Website: NHS Sickle Cell and Thalassaemia Screening Programme Website: The UK Thalassaemia Society Tel: Fax: office@ukts.org Website: UCL Hospitals cannot accept responsibility for information provided by external organisations.

10 10 Space for notes and questions

11 Space for notes and questions 11

12 First published: November 2015 Last review date: November 2015 Next review date: November 2017 Leaflet code: UCLH/S&C/CD/JRCU/EXJADETMTIO/1 University College London Hospitals NHS Foundation Trust