Iron overload causes the most mortality and morbidity. Iron deposition occurs in important organs, especially the heart, liver, and endocrine glands causing tissue damage and ultimately organ dysfunction and failure. Humans do not have a mechanism to express iron overload, so chelation therapy is needed. Iron chelating is a chelating agent that can bind excess iron in the body so that it can be removed from the body. Therapy should be started as soon as possible when iron deposits are sufficient to cause tissue damage, namely after 10-20 transfusions or when ferritin levels increase above 1000 micrograms per liter.

Iron is an important metal for hemoglobin synthesis, oxidation-reduction reactions and cell proliferation, while excess iron will cause organ dysfunction through the production of reactive oxygen species. The amount of iron in the body ranges from 3-4 g, two thirds is in the red blood cells and is recycled by the destruction of erythrocytes; the remainder is stored in the form of ferritin/hemosiderin, while only 1-2 mg of iron is absorbed through the gastrointestinal tract and circulates in the blood. Body iron metabolism is a semi-closed system, and is critically regulated by several factors including hepcidin. In the bloodstream, iron is usually bound to transferrin and most of the iron bound to transferrin is used by the bone marrow for erythropoiesis. Due to the absence of an active mechanism in the body to excrete iron, a progressive accumulation of body iron is likely to occur as a result of prolonged transfusion in patients with thalassemia. 3

It has long been known that deferoxamine (desferal) is the standard reference for iron chelation therapy in thalassemia patients, but in several studies, the results of low levels of adherence to the use of these drugs have been found. Currently, the latest chelation therapy with oral preparations has been developed, namely deferasirox (trade name: Exjade). It is hoped that with the oral chelation therapy, the patient’s level of compliance in taking the drug will be better and can reduce the effects of morbidity and mortality due to iron overload in thalassemia patients. This paper will discuss deferasirox (Exjade) as iron chelation therapy. 3

Deferasirox belongs to the tridentate iron group. 2 molecules of deferasirox bind 1 molecule of iron. Deferasirox contains inactive ingredients such as lactose monohydrate, crospovidone, povidone (K30), sodium lauryl sulfate, microcrystalline cellulose, silicon dioxide and magnesium stearate. deferasirox is an orally active iron binder consisting of more than 700 components. The ICL 670 component is the result of a combination of modern chemical development programs with traditional chemical development techniques. 3

Derairox mechanism of action
Deferasirox has a very high affinity and specificity for Fe3+. The active molecule of deferasirox is highly lipophilic and has a relatively smaller molecular weight compared to deferoxamine due to its ability to enter cells and remove iron. Together with its long enough presence in plasma, it has the potential to maximize the chelating effect of stored iron at relatively small, easy-to-reach levels, maximize clearance of stored iron and minimize uncontrolled iron storage.

Excess iron is found in 2 forms, namely LPI (labile plasma iron) and LCI (labile cell iron). LPI is present in the circulation, namely Fe that is not bound by transferrin, while LCI is intracellular Fe that is not bound to ferritin or hemosiderin. Deferasirox works to bind LPI and LCI because of its hydrophilic nature so that it can penetrate intracellularly. As much as 90% of deferasirox is excreted in the feces.

Excessive erythropoiesis, anemia of chronic disease, and hypoxia will increase intestinal iron absorption. When serum transferrin increases to 70%, ferritin will be damaged and cause hemosiderin to increase and free iron species will be found in plasma which will increase reactive oxygen species which will cause tissue damage, organ dysfunction, and death. Deferasirox acts on the cytosolic ferritin iron. Binds iron and excretes it in the urine

Figure 1. Binding of free iron species with iron chelate.

Figure 1. Binding of free iron species with iron chelate.

Figure 2. The mechanism of action of iron chelation in preventing ROI and ROS

Figure 2. The mechanism of action of iron chelation in preventing ROI and ROS

Gambar 3. Mekanisme kerja kelasi besi melalui kompartemen subselular yang berbeda

Gambar 3. Mekanisme kerja kelasi besi melalui kompartemen subselular yang berbeda

One dose of oral deferasirox is more potent than one subcutaneous non-continuous dose of desferoxamine and 10 times more potent than one oral dose of deferipron.

The potential and specific ability of deferasirox to mobilize tissue iron and to increase its excretion has been demonstrated in several animal studies. Administration of single and multiple doses of iron in experimental rats and guinea pigs increased iron excretion, especially in feces. Administration of deferasirox for a long time, namely in rats for 12 weeks and guinea pigs for 39 weeks, showed a significant decrease in iron levels in the liver. This indicates that the main storage site for iron in the body is the target organ of deferasirox. 2.6

Deferasirox has a relatively smaller molecule and is lipophilic so that in addition to binding to labile plasma iron (LPI), namely Fe which is not bound to transferrin, it is also able to penetrate intracellularly which is able to bind labile cell iron (LCI), namely Fe which is not bound to ferritin or hemosiderin. . LPI and LCI will form ROI and ROS which eventually causes cell death, so that by binding LPI and LCI by deferasirox, ROI and ROS can be prevented. However, if ROI and ROS have been formed, deferasirox no longer works. 90% of deferasirox is excreted in the feces.


  1. Kohgo, al. Body iron metabolism and pathophysiology of iron overload. 2008, International Journal of Hematology, Vol. 88, pp. 7-15
  2. Spesific iron chelator determine the route of ferritin degradation. Blood. 2009:4546-51.
  3. Taher A, Capellini. 2007.Update on the Use of Deferasirox in the Management of Iron Overloaded. Therapeutics and Clinical Risk Management.
  4. Cabanthick ZI. Nontransferin bound iron and labile plasma iron in relation to iron toxicity. Institute of Life Science.San Fransisco. 2014.
  5. Rahmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2010:3479-86
  6. Debaun, MR. Vichinsky Elliot, Hemoglobinopathy, Thalassemia. Nelson Textbook of Pediatrics, 18 th edition, 2007.

By :

dr.Mahirina Marjani, SpA, Dr.dr.Nadirah Rasyid Ridha,M.Kes,Sp.A(K), Prof.Dr.dr.H.Dasril Daud,Sp.A(K)






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