DESFERAL TOXICITY
There is only one safe and effective iron chelator available today: Desferal. Desferal (desferrioxamine) was isolated from a bacteria, Streptomyces pilosus, in the 1960's. Initially it was developed as an antibacterial agent, and later as a delivery vehicle for iron. Eventually, it was used as an iron chelator for children who had iron overload (hemosiderosis) from transfusion. It was not a particularly effective chelator until the introduction of small pumps to infuse the chelator over many hours.
Desferal can be used subcutaneously or intravenously to remove iron from children and adults who have hemosiderosis secondary to transfusions or ingestion. It is well documented that continuous use of this agent can produce a negative iron balance and is very effective in removing iron from the body. It is more effective is used with ascorbic acid (vitamin C). Vitamin C must be used only with Desferal in iron overloaded individuals, since larger doses without Desferal can cause an increase in free iron and increased toxicity, particularly cardiac toxicity.
An oral iron chelator (L-1 or deferiprone) has been studied and found to be less effective than Desferal. Recently, it has been shown to have severe side effects when used for many years. This drug has not been released by the Food and Drug Administration, and further testing is being done with this drug in the United States and around the world. This medication is used in countries where the potential side effects of hemosiderosis outweigh the dangers if L-1. There are numerous other chelators being developed, including a long-acting form of desferrioxamine.
Desferal itself has several side effects. The most common is irritation at the site of administration. Using more normal saline or sterile water to mix the Desferal makes it much less irritating. Usually Desferal is mixed as 500 mg/2 cc: a 25% solution; less irritating is a 12.5% solution. Occasionally, the needle is not in the subcutaneous space and blisters leading to scarring can occur.
A less common problem is ringing of the ears (tinnitis). This requires a formal hearing evaluation by a qualified audiologist to determine whether any changes need to be made in the Desferal dose. Desferal usually causes high frequency hearing loss, at frequencies that would not be detected or appreciated by the affected individual.
Decreased night vision is much less common but occasionally occurs. There can also be retinal changes that can only be detected by an experienced opthalmologist.
Allergic reactions can be a problem and require desensitization. Desensitization requires hospitalization and monitoring. Once desensitization has been achieved, Desferal must be used nightly to maintain tolerance. If it is discontinued for more than 48 hours, severe allergic reactions or anaphylaxis can occur.
Cartilageous dysplasia of the long bones and spine as well as decreased linear growth has been described in young children who used Desferal.
High dose Desferal can cause renal problems in children and adults who have preexisting renal disease, as well as in apparently healthy individuals. There can be increase in plasma creatinine and diuresis, with the urine output exceeding the intake. Desferal has caused an increase in electrolyte excretion in some individuals given the drug intravenously. Hypotension can also be a side effect of high dose intravenous Desferal.
Pulmonary fibrosis has been described in some adults who have used Desferal. Desferal is discontinued with fevers and infection. Desferal promotes some bacterial infections, in particular Yersinia enterocolitica gastroenteritis.
A toxicity index is used in some centers: the mean daily dose of Desferal in mg/kg/serum ferritin (mg/dl) < or = 0.025. However, ferritin is an acute phase reactant and can be elevated during inflammatory processes, in particular hepatitis.
