Edetate disodium is a chelating agent with affinity for divalent and trivalent metals. Because the drug can decrease blood calcium levels too rapidly (causing tetany, cardiac arrhythmias, and respiratory arrest), it now is only rarely used. Due to its pharmacodynamic actions that oppose those of the cardiac glycosides, edetate disodium was once used to treat arrhythmias associated with digitalis toxicity, but digoxin immune Fab is now the preferred agent for this condition. Edetate disodium should not be confused with its calcium salt (calcium EDTA), which is used to treat lead toxicity. In the 1950s and 1960s, edetate disodium was used for atherosclerotic vascular disease despite a lack of clinical data to support its efficacy. Only 1 large, placebo-controlled, randomized, double-blind study has been conducted to evaluate this use of edetate disodium and this study showed no significant symptomatic or angiographic improvement in the EDTA group relative to placebo.Sloth-Nielsen J, Guldager B, Mouritzen C, et al. Arteriographic findings in EDTA chelation therapy on peripheral arteriosclerosis. Am J Surg 1991;162:122-5. Nevertheless, there continues to be sustained interest in using this drug for the treatment of atherosclerosis. Based on a recent clinical trial (PATCH), there is no evidence to support a benefit (evaluated exercise time to ischemia, exercise capacity, and quality of life measurements) of chelation therapy (Endrate®) in patients with ischemic heart disease including stable angina.Knudtson ML, Wyse DG, Galbraith PD, et al. Chelation therapy for ischemic heart disease: a randomized controlled trial. JAMA 2002;287:481-6. Because of the possibility of potentially lethal adverse effects, edetate disodium should not be used for the treatment of generalized arteriosclerosis due to advancing age. Edetate disodium was approved by the FDA for clinical use in 1956.
The cardiac status of the patient should be determined before administering edetate disodium. The drug’s negative inotropic effects could adversely affect a patient with cardiac disease (incipient congestive heart failure or limited cardiac reserve), so the drug should be used cautiously in such patients. Because of the high sodium content of the drug, edetate disodium also should be used cautiously in patients who require sodium restriction.
Rapid intravenous administration may cause a precipitous fall in the serum calcium concentration, which could result in death; toxicity has been directly related to the total dose and rate of infusion. Because edetate disodium chelates and reduces serum calcium, it should not be used in patients with hypocalcemia or in patients with normal serum calcium values. Edetate disodium should be used with caution in patients with a seizure disorder or intracranial lesions because the drug-induced hypocalcemia can precipitate seizures.
Although the drug does not chelate potassium, the administration of edetate disodium can increase renal excretion and decrease serum concentration of this mineral, possibly producing hypokalemia. Therefore, the drug should be used with caution in patients with a potassium deficiency. In addition, hypomagnesemia may occur after prolonged administration; monitor serum electrolytes carefully during therapy.
Edetate disodium is contraindicated in patients with anuria. Use with caution in those with renal failure or renal impairment; edetate disodium may contribute to decreased renal function. Perform assessments of renal function during edetate disodium treatment. To the extent that geriatric patients may be more likely to have renal function impairment, caution should be used upon administration to elderly patients.
Because edetate disodium may cause postural hypotension, patients should remain in bed for a short time after the infusion.
Edetate disodium should not be used in patients with calcified tubercular lesions that have healed or in patients with active tuberculosis.
Edetate disodium may cause hypoglycemia and a reduction in insulin requirements in patients with diabetes mellitus; monitor blood glucose carefully during treatment.
Edetate disodium is classified as FDA pregnancy risk category C. No adequate and well-controlled studies have been conducted in pregnant women, and its ability to cause fetal harm or affect reproductive capacity is unknown. Therefore, the manufacturer recommends use during pregnancy only if clearly needed.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Data are limited regarding use of edetate disodium during breast-feeding and its excretion in human milk is unknown. Due to the drugs short elimination half-life (1 hour), significant presence in breast milk is not expected. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Safety and efficacy of edetate disodium have not been established in children.
Edetate disodium is classified as FDA pregnancy risk category C. No adequate and well-controlled studies have been conducted in pregnant women, and its ability to cause fetal harm or affect reproductive capacity is unknown. Therefore, the manufacturer recommends use during pregnancy only if clearly needed.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Data are limited regarding use of edetate disodium during breastfeeding and its excretion in human milk is unknown. Due to the drugs short elimination half-life (1 hour), significant presence in breast milk is not expected. Consider the benefits of breastfeeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Calcium Carbonate: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Calcium Carbonate; Magnesium Hydroxide: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Calcium Carbonate; Risedronate: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Calcium Salts: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Calcium: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Calcium; Vitamin D: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Carbetapentane; Guaifenesin; Phenylephrine: Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Carbetapentane; Phenylephrine: Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Cardiac glycosides: The pharmacodynamic actions of edetate disodium oppose those of the cardiac glycosides.Lanoxin® (digoxin) package insert. Research Triangle Park, NC: Glaxo Smith Kline; 2001 Aug.
Chlorpheniramine; Pseudoephedrine: Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Chromium: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Collagenase: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Cyanocobalamin, Vitamin B12: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Digitoxin: The pharmacodynamic actions of edetate disodium oppose those of the cardiac glycosides.Lanoxin® (digoxin) package insert. Research Triangle Park, NC: Glaxo Smith Kline; 2001 Aug.
Digoxin: The pharmacodynamic actions of edetate disodium oppose those of the cardiac glycosides.Lanoxin® (digoxin) package insert. Research Triangle Park, NC: Glaxo Smith Kline; 2001 Aug.
Guaifenesin; Phenylephrine: Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Hetastarch; Dextrose; Electrolytes: Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan. Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Insulins: Use caution in administration of calcium EDTA to patients with diabetes mellitus who are receiving insulin therapy. Calcium EDTA chelates the zinc in selected exogenous insulins, thereby increasing the amount of insulin available to the body and decreasing the duration of the insulin dose. Alterations in blood glucose control may result. Diabetic patients receiving calcium EDTA may require adjustments in their insulin dosage.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Iron Salts: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Magnesium Citrate: Administration of oral magnesium citrate with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Magnesium Salts: Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium,EDTA Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan. Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Magnesium: Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Melatonin: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Pantothenic Acid, Vitamin B5: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Succimer: Concomitant use of succimer and other chelation therapy such as edetate calcium disodium, calcium EDTA (CaNa2EDTA) with or without dimercaprol (BAL) is not recommended, as data are not available. Patients who have received CaNa2EDTA with or without dimercaprol may use succimer for subsequent treatment after an interval of 4 weeks.Chemet (succimer) package insert. Seymour, IN: Schwarz Pharma Mfg, Inc.; 2009 May.
Thiamine, Vitamin B1: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21.
Zinc Salts: Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.Waters RS, Bryden NA, Patterson KY, et al. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res 2001;83:207—21. Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Zinc: Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.Calcium Disodium Versenate® (edetate calcium disodium injection,USP) package insert. North Chicago, IL: Abbott Laboratories; 2000 Jan.
Chronic administration of edetate disodium can cause dermatitis resulting in lesions similar to those seen with vitamin B6 deficiency, which may be due to zinc depletion.
Edetate disodium administration may induce laboratory abnormalities, including certain electrolyte imbalance, hepatic enzyme changes, hyperuricemia, and anemia. Hypocalcemia and hypokalemia could be seen soon after drug administration. Appropriate monitoring of blood labs and cardiac function should be performed throughout treatment as clinically indicated, particularly in patients with ventricular arrhythmia, seizure disorder, or intracranial lesions. Intravenous calcium replacement (e.g., calcium gluconate) may also be necessary. Hypomagnesemia is possible with prolonged therapy. If clinical evidence suggests any disturbance of liver function during treatment, appropriate laboratory determinations should be performed and withdrawal of the drug may be required.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Thrombo-phlebitis, febrile reactions (fever), exfoliative dermatitis, and other toxic skin and mucous membrane reactions have been reported with edetate disodium administration. Irritation of the tissues resulting in an injection site reaction may be seen if appropriate dilution has not occurred prior to administration.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Adverse GI symptoms often occur during edetate disodium administration and can include diarrhea, nausea, and vomiting.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Following administration of edetate disodium, disodium EDTA, transient symptoms such as circumoral paresthesias, numbness, and headache may occur. Orthostatic hypotension may also occur; having the patient remain in bed for a short time after the infusion should alleviate this.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
High doses of edetate disodium can result in hemorrhagic damage to the reticuloendothelial system and in nephrotoxicity. Nephrotoxicity is manifested as nocturia, urinary urgency, polyuria, dysuria, oliguria, proteinuria, renal failure, or (rarely) acute renal tubular necrosis. It usually is related to excessive doses and typically is reversible within a few days of drug discontinuation.Endrate (edetate disodium, anhydrous injection) package insert. Lake Forest, IL: Hospira, INC.; 2004 May.
Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.
