Deferasirox treatment for iron overload : University College London Hospitals NHS Foundation Trust

What is deferasirox?

Deferasirox is a type of medicine called an iron chelator. It works by binding to iron and removing it from your body.

We all need iron in our body. Our body usually regulates iron levels by absorbing more from our diet when our levels are low and less when we have plenty. Too much iron can build up when our body doesn't regulate it well. This can happen to people who have a genetic condition called haemochromatosis. Iron can also build up after regular blood transfusions or in conditions like thalassemia. For people who have thalassemia, the body absorbs extra iron to counteract the anaemia, even when there is enough iron.

Too much iron can damage tissues where it builds up, mainly in the liver. It can cause:

Liver scarring (fibrosis)
Severe liver damage (cirrhosis)
Liver failure.

It can take a long time for problems to show up. This is because the liver is good at handling extra iron compared to other organs.

In people with transfusion-dependent thalassaemia, iron can also build up in the heart. This can lead 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.

Deferasirox helps remove excess iron from the liver and heart, reducing damage. It is used by people with transfusion-dependent thalassaemia, sickle cell disorder or anaemias. It can also be used by people with non-transfusion-dependent thalassemia, even if they haven’t had blood transfusions.

Deferasirox is absorbed through the gut and into the bloodstream. It binds to iron either in the bloodstream or in tissues, such as the liver or heart. Once deferasirox binds to the iron, it is eliminated from the body in poo. Very little iron is removed through pee. So, it doesn’t cause pee to turn red unlike other similar medicines such as Desferal®.

Deferasirox comes in a tablet that you swallow. You take it once a day either on an empty stomach or with a light meal. Taking it at the same time each day will help you to remember to take it. If you can’t swallow the whole tablet, you can crush it and sprinkle it on to soft food, such as yogurt or apple puree. You will need to eat the food immediately and finish the whole portion – you should not keep it to eat later.

The dose you take depends on how much iron is in your body and how fast iron is building up. If you have regular blood transfusions, a higher dose may be needed to match the rate the iron builds up. This does not apply if you get blood through an automated exchange transfusion, which is a type of treatment used for some people with sickle cell disorder. If the iron builds up slower than it has in the past, a smaller dose will usually be needed to lower the iron levels in your body. As the iron levels fall, the dose may be reduced. Doses often need to reduce when ferritin falls below 1000µg/L or if the fall in ferritin is too rapid.

If we keep giving high doses of deferasirox when your iron levels drop, there’s a risk of ‘over-chelation,’ which can lead to more side effects. To avoid this, we’ll monitor your iron levels closely and adjust your dose if necessary.

If taking deferasirox alone doesn’t lower your iron levels enough, it can be combined with another chelator. There is lots of evidence that using deferasirox with another chelator is effective and generally well tolerated.

We’ll check your iron levels in your blood. Whether they go up or down will tell us how well the treatment is working. This is the same as with other chelator treatments.

An MRI scan of your liver and heart can be done to check the amount of iron in your body and if the dose needs to be adjusted. You will have an MRI scan about once a year.

Like any medicine, deferasirox causes side effects. These are more likely if the dose is too high.

The side effects of deferasirox have been carefully studied in large clinical trials. So, we have a good understanding of how often they happen.

The most common side effects include:

Mild stomach discomfort pain, nausea, vomiting, diarrhoea and constipation (lasting about eight days). If you have these symptoms, it is unlikely that we will adjust the dose of deferasirox or stop it. If the symptoms persist, please talk to the doctor who prescribed it. These symptoms normally occur in about 15 out of 100 people.
Stomach ulcers. These are rare but are more likely to happen when deferasirox is given with medicines that irritate the stomach, such as some painkillers.
Skin rashes. These occur in about 11 out of 100 people. These are usually red and itchy (sometimes raised) bumps. They may occur all over the body or can be limited to your palms and feet. The rash typically develops within two weeks of starting treatment. If this happens, the dose of deferasirox can be reduced for a short time. Sometimes steroids can be given for the rash. Very rarely deferasirox needs to be stopped permanently.
Raised markers of kidney function. Sometimes, deferasirox can cause a temporary increase in a blood marker called serum creatinine, which shows how well your kidneys are working. In about 30 out of 100 people, this marker might go up by around 30%. This usually isn’t a big problem. However, if the increase is higher or lasts too long, we might need to lower your dose or pause the treatment for a bit.
Abnormal liver function. Typically, this resolves as iron levels decrease. In fewer than 1 in 100 people, liver enzymes are greater than twice the normal upper level. If this happens, a break in treatment might be needed. Your liver function will also be closely monitored during treatment.

Deferasirox does not cause joint pain or affect your white blood cell count, unlike Ferriprox®. So, weekly blood tests are not needed.

Deferasirox over-treatment is not typically linked with hearing or eyesight problems, unlike Desferal®. All patients still have their hearing and eyesight checked as a precaution. Rarely, cataracts have been reported with both Desferal® and deferasirox.

Deferasirox at current recommended doses does not seem to affect growth in children, unlike Desferal®.

In clinical trials comparing deferasirox to Desferal®, patients reported better satisfaction and quality of life with deferasirox. They also reported that it was more convenient to use than Desferal®.

We will monitor you regularly to avoid under or over-treatment. We will do some tests more often when you start the treatment or if the dose changes (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-to-creatinine ratio. Serum creatinine levels are checked when you have your regular blood tests before each transfusion. Urine tests are done at the same time.
Liver function tests – these should be done when you have the cross match. This is usually once a week for four weeks when treatment starts or the dose is increased.
Vision and hearing tests – hearing tests are done every one or two years. Vision tests are done during your thalassaemia or sickle cell follow-up appointment. They are not done specifically because you take deferasirox.

For more information about chelation therapy, please see our web page, Treatment options for iron overload.

Haematology admin team:

uclh.redcelladminteam@nhs.net

Haematology clinical nurse specialists (CNSs):

uclh.redcell.cnsteam@nhs.net

Haematology advice line (office hours, adults and children):

020 3447 7359

Adult haematology advice line (out of hours):

07852 220 900

Paediatric helpline (out of hours):