Clinical Pharmacology and Toxicology of the Current and New Potential Therapeutic Agents for the Treatment of Iron Overload
Iron poisoning has been linked to morbidity and mortality due to iron overdose or chronic iron deposition in the body. It is a big challenge to treat the iron overload associated diseases including hemochromatosis, thalassemia and sideroblastic anemias. Although, therapeutic phlebotomy is still the cornerstone therapy in the patients with hereditary hemochromatosis and other blood disorders, yet chelation therapy is currently used and is in the continuous process of development for the patients with iron overload associated diseases. Patients requiring transfusions over lifetime have iron accumulation in multiple organ systems including liver, heart and endocrine system, which could ultimately lead to organ failure. Therefore, iron-chelation is a necessary step to prevent organ failure and reduce mortality resulting from an acute or chronic iron poisoning. The availability of the wide variety of chelating agents in the market makes the treatment of iron poisoning more challenging and socioeconomic problem in healthcare. Recently, the clinical studies on existing and new chelating agents have been expanded considerably to include disorders associated with iron overload or diseases in which the iron plays a key role in the pathophysiology. Since, last several years there is an increase in the unapproved over the counter (OTC) chelation products marketed with claims to prevent or treat diseases. The US Food and Drug Administration (FDA) has raised concern over the use of several unapproved OTC chelation products, and has issued warnings against unproven claims of these chelation therapies. The current review presents the clinical pharmacology, clinical indications and toxicity of the recommended iron-chelating agents such as deferoxamine, deferiprone, and deferasirox for the treatment of iron overload. The recent advances in finding the new chelating agents including the desferrithiocin derivative and currently available calcium channel blockers undergoing the clinical trials for the treatment of iron overload are also discussed.