Deferasirox

Deferasirox is the first orally-administered drug approved in the United States for the treatment of iron overload in people with anemia who are receiving blood transfusions. It belongs to a family of drugs called iron chelators. Other members of this family include deferiprone (Ferriprox) and deferoxamine (Desferal). Iron chelators bind to iron and facilitate its removal from the body. The Food and Drug Administration approved deferasirox in November 2005. Deferasirox is marketed as Exjade by Novartis.

Uses

Deferasirox is indicated for the treatment of chronic iron overload due to long-term use of blood transfusions. This form of iron overload is called transfusional hemosiderosis and occurs in people who need transfusions because of anemia (a deficiency in the number of red blood cells or the oxygen-carrying capacity of these cells). Deferasirox is used in children 2 years of age or older and adults.

How Deferasirox is Taken

Deferasirox is supplied in tablets of 125 mg, 250 mg, and 500 mg. The recommended initial dose is 20 mg/kg of body weight daily. Dosing is sometimes adjusted thereafter. However, the risk of toxicity is high if the daily dose exceeds 30 mg/kg.

The tablets can be dispersed in liquid and not swallowed whole. Food may affect the absorption of the drug. To avoid this, the drug can be taken on an empty stomach (at least 30 minutes before a meal).

How Deferasirox Works

Iron is an integral component of hemoglobin, the molecule that carries oxygen in red blood cells. Use of blood transfusions over the long-term can overload the recipient’s blood with iron. This iron overload can cause damage to organs, primarily the liver and heart.

Deferasirox is an iron chelator. It strongly binds to iron and facilitates its excretion in the feces. In the process, two deferasirox molecules form a complex with an iron atom. Deferasirox removes iron from the blood as well as liver and heart cells.

How the Body Affects Deferasirox

Peak circulating levels of deferasirox are reached 1.5–4 hours post-dosing. The half-life of deferasirox, the time needed for the concentration in the blood to be reduced by half, is 8–16 hours. Because of this long half-life, the drug is taken once a day. Deferasirox is mainly metabolized by enzymes in the liver called UGT1A1 and UGT1A3. Deferasirox is mainly eliminated from the body in the feces.

Side Effects

The most common side effects of deferasirox are the following:

• diarrhea
• headache
• abdominal
• fever
• cough
• increased serum creatinine, a sign that the kidneys are not filtering the blood efficiently

Risks and Precautions

• Some reports have surfaced of kidney impairment associated with deferasirox use. Blood tests are used to determine kidney function during treatment in people at high risk of kidney complications (see video below).

• Deferasirox could cause a severe deficiency in the number of blood cells (cytopenia). Complete blood counts during treatment can detect an abnormal drop in the number of blood cells.

• Liver failure, sometimes leading to death, has been reported during treatment of people with pre-existing, severe liver damage such as cirrhosis or multi-organ failure. Liver tests are performed while receiving deferasirox to reduce the risk to the liver (see video below).

• Dizziness while receiving deferasirox may impair driving or the operation of machinery.

Drug Interactions

Deferasirox can bind to aluminum released from some antacids. However, deferasirox binds more readily to iron. The risk of an interaction is minimal if deferasirox is not taken within two hours of an aluminum-containing antacid.

Deferasirox is contraindicated in people already taking an iron chelator because of the increased risk of toxicity.

alternatives

Deferoxamine (Desferal) is another form of deferasirox that is designed to be given intravenously. Deferasirox was developed to overcome difficulties with the administration of deferoxamine.

Research

The Food and Drug Administration granted approval of deferasirox based on the results of a clinical trial of patients two years of age or older who had beta-thalessemia. ^[1] Deferasirox significantly reduced iron concentrations in the liver, a generally accepted indicator for total body iron levels, in both the adults and children receiving blood transfusions.

References

1. ↑ Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood. 2006 May 1;107(9):3455-62. Abstract | Full Text | PDF | Press Release

External Links

FDA: Patient Information Sheet