Edetic acid and its salts

General information

Edetic acid is a metal chelator. The effect of an intravenous dose of 1 g of calcium disodium edetate on the urinary excretion on the elements aluminium, boron, barium, calcium, copper, iron, lead, magnesium, manganese, phosphorus, potassium, silicon, sodium, strontium, sulphur, and zinc was measured in healthy volunteers. The ratio of the increase of urinary elimination was about two for iron, five for aluminium, lead, and manganese, and 15 for zinc [ ].

Salts of edetic acid are still used in intravenous “chelation therapy” as an alternative treatment for atherosclerotic disease in several countries [ ]. Many of the data on their adverse effects are derived from older studies. There is some evidence of efficacy, although the dangers are obvious [ , ].

Urea edetate (with methylhexyl ether) has been used for the dissolution of calcified gallbladder stones, without adverse effects [ ].

A newly identified inherited disorder in a 12-year-old girl, characterized by manganese storage, dystonia, polycythemia, and liver injury, was successfully treated with monthly infusions of calcium disodium edentate 40 mg/kg/day for 5 consecutive days [ ]. Penicillamine had previously been ineffective.

Adverse reactions to disodium edetate include hypocalcemia, tetany, convulsions, cardiac dysrhythmias, respiratory arrest, and renal insufficiency. Other possible symptoms include nausea, vomiting, diarrhea, fever, headache, and urinary urgency. Pain and phlebitis at the site of injection can occur [ ]. The sodium load in “chelation therapy” can precipitate heart failure. Renal tubular necrosis can occur [ ]. Sodium calcium edetate can cause the same adverse effects as the disodium salt, with the exception of hypocalcemia.

In children receiving disodium ethylenediaminetetra-acetate by intravenous infusion, an influenza-like syndrome developed, characterized by lacrimation, rhinorrhea, sneezing, and cough [ ]. Other symptoms included malaise, fatigue, nausea, and vomiting; one patient had a fever of 39.2°C.

Five patients became ill shortly after chelation therapy at an out-patients clinic, where they had received an infusion of Na ₂ EDTA 3 g, MgCl 2 g, vitamin B ₁ 100 mg, vitamin B complex 1 ml, and vitamin C 15 g in sterile water at a rate of 180 ml/hour [ ]. One patient also received 10 ml of 50% dimethylsulfoxide. All initially had gastrointestinal and musculoskeletal symptoms (trembling, muscle spasms) and complained of dry mouth or excessive thirst. All had fever and hypotension, four had tachycardia and sweating. Laboratory data were collected in four patients, all of whom had varying degrees of thrombocytopenia, leukopenia, and lymphocytopenia, reflecting transient bone marrow suppression. Subsequent measurements showed leukocytosis with early cell forms. Urinalysis showed transient proteinuria (in four), microscopic hematuria (in three), hyaline casts (in two), and ketonuria (in four). Three had mild transient rises in serum urea and creatinine concentrations. Three had hypocalcemia, requiring supplementation in one (probably accounting for the muscular symptoms). In these patients, acute edetate toxicity appeared to be related to errors in dosage or the rate at which the formulation was administered.

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