Chelation Therapies



Iron Reduction: Chelation Therapy

Definition: Iron chelation therapy is the removal of excess iron from the body with special drugs.  Chelate is from the Greek word “claw”.

Patients who have anemia (low hemoglobin) and iron overload at the same time cannot tolerate phlebotomy (blood donation). These patients need iron chelation therapy to remove the iron.

Anemia with iron overload is prominent in several conditions such as sickle cell disease, thalassemia major, myelodysplasic syndromes (MDS), enzyme disorders, iron transport or storage disorders, and some forms of cancers.  Patients with these conditions require repeated blood transfusions to survive.

Each unit of blood used in transfusion contains about 250 milligrams of iron. The body cannot excrete iron, except in tiny amounts-about one milligram per day, which is sloughed off in skin or perspiration. Therefore the excess iron is trapped in the tissues of vital organs, such as the anterior pituitary, heart, liver, pancreas and joints. When the iron reaches toxic levels, damage can result in diseases such as diabetes, cirrhosis, osteoarthritis, heart attack, and hormone imbalances. Hypothyroidism, hypogonadism, infertility, impotence and sterility can result from these hormone imbalances. The patient can experience symptoms of chronic fatigue, mood swings, loss of sex drive, confusion, and memory loss. If not addressed, excess iron can result in complete organ failure and death.

It is important to remove the unnecessary iron before damage can occur. Iron reduction is accomplished with chelation therapy, which is the removal of iron pharmacologically with an iron-chelating agent such as desferrioxamine, brand name Desferal or deferasirox, brand name Exjade. Both of these products are manufactured by Norvartis Pharmaceuticals and are currently the only two iron chelator drugs approved for use in the US. These drugs are specifically formulated to bind with iron so that the iron can be excreted in urine.

Other types of chelation
The type of chelation therapy used to de-iron patients should not be confused with EDTA (ethylenediaminetetra-acetic acid), a method used by some alternative medicine practitioners. EDTA is a broad-spectrum chelator, meaning that it binds with and removes a wide number of minerals, including iron, but it is not specific to iron.

Deferrioxamine, brand name Desferal is not absorbed in the intestinal tract; therefore, this drug must be administered intravenously at an infusion center. Or the drug can be given subcutaneously, using a portable battery-operated infusion pump. Generally, the pump is worn at night, where slow infusion of the iron chelating agent is administered over a period of about eight hours, for the duration of four to six nightly infusions per week. Patients are given a step-by-step demonstration of how to sterilize the skin, insert the needle and operate the pump. 

Before Desferal is administered by either method, a test dose is given to be certain that there are no immediate reactions to the drug. Desferal is administered slowly at first, beginning with 1.0 gram, three to four times per week with monitoring of iron excretion in a cumulative 24-hour urine sample. If effective, the dose can then be adjusted upwards, one gram at a time, up to four times per week, until the patient reaches a tolerable level. The dose should not to exceed 50 milligrams/kg weight, or about 3 grams per day. Periodic examination of the patient is necessary until positive response to treatment is confirmed. Patients might be given an additional two grams of Desferal intravenously for each unit of blood transfused. Desferal is injected separately from blood transfusions.

Desferal has been approved for use in the USA since the late 1970’s. Deferiprone also called L1, brand name Ferriprox is different from Desferal in that Ferriprox can be taken orally. In August of 1999, Apotex Inc., the Canadian Pharmaceutical Manufacturer of Ferriprox was granted approval in Europe by the European Agency for the Evaluation of Medicinal Products to use the oral chelator for treatment of iron overload in patients with thalassemia when desferrioxamine therapy is contraindicated or in those who develop serious toxicity with desferrioxamine therapy. Ferriprox is not approved for use in the USA.

The primary role of iron-chelation therapy is to prevent premature death from heart attack due to myocardial iron overload. Statistically 50% of patients with thalassemia major die of heart attack before the age of 35, primarily due to iron-related heart failure.

Side effects of IV iron chelation:

The urine can become orange colored, which is a harmless side effect. Immediate symptoms of adverse reaction to IV iron chelation therapy might include: visual disturbances, blurred vision, rash or hives, itching, vomiting, diarrhea, stomach or leg cramps, fever, rapid heart beat, hypotension (low blood pressure), dizziness, anaphylactic shock, and pain or swelling at site of intravenous entry. Long term problems might include kidney or liver damage, loss of hearing or cataracts.

Patients should report such symptoms immediately to their physician who can adjust dosage. Further, physicians might examine patient’s visual status with slit-lamp fundoscopy (examination of the eye) and hearing status with audiometry or hearing test. Liver enzymes (ALT, AST, GGT and ALP), a kidney function test such as BUN, serum ferritin and transferrin iron saturation percentage might also be measured by the attending physician.

Limitations of Desferal

Nursing mothers will need to talk with their physicians about iron chelation drugs.  It is not known how much of the drug gets into breast milk; thus, a mother who is receiving Desferal treatment might consider low iron soy formula substitutes.

When to begin iron chelation therapy

Initiating chelation therapy depends upon several factors: the patient’s overall health, hematologic values, especially hemoglobin, hematocrit and the tissue iron levels. Tissue iron is determined by measuring serum ferritin, and fasting serum iron and TIBC (total iron-binding capacity). Transferrin-iron saturation percentage (TS%) can be calculate with these last two tests (serum iron divided by TIBC multiplies by 100%). The results from these tests can be used to monitor iron build up and to address the excess iron as soon as possible. Some physicians will begin iron chelation therapy when serum ferritin is between 1,000-1,500ng/mL. Serum ferritin that is above 2,500 ng/mL before beginning iron chelation therapy might result in organ damage. 




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