Sodium Calcium Edetate

(BAN, rINN)
Sodium Calcium Edetate Chemical formula
Synonyms: Calcioedetato de sodio; Calcium Disodium Edathamil; Calcium Disodium Edetate; Calcium Disodium Ethylenediaminetetra-acetate; Calcium Disodium Versenate; Calcium édétate de sodium; Calcium EDTA; Disodium Calcium Tetracemate; E385; Edetan sodno-vápenatý hydrát; Edetate Calcium Disodium um-nátrium-edetát; Natrii calcii edetas; Natrii Calcii Edetas Hydricus; Natrio-kalcio edetatas; Natriumkalciumedetat; Natriumkalsiumedetaatti; Sodium, calcium édétate de; Sodium Calciumedetate; Sodu wapnia edetynian; Sodyum Kalsiyum Edetat; Wapniowo-disodowy edetynian. The calcium chelate of disodium ethylenediaminetetra-acetate; Disodium[(ethylenedinitrilo)tetraacetato]calciate(2−) hydrate.
Cyrillic synonym: Натрия Кальция Эдетат.

💊 Chemical information

Chemical formula: C10H12CaN2Na2O8,xH2O = 374.3 (anhydrous).

Pharmacopoeias.

In Chin., Eur., Int., US, and Viet.

Ph. Eur. 6.2

(Sodium Calcium Edetate). A white or almost white, hygroscopic, powder. Freely soluble in water; practically insoluble in alcohol. A 20% solution in water has a pH of 6.5 to 8.0. Store in airtight containers. Protect from light.

USP 31

(Edetate Calcium Disodium). White, slightly hygroscopic, odourless, crystalline powder or granules. Freely soluble in water. pH of a 20% solution in water is between 6.5 and 8.0. Store in airtight containers.

💊 Adverse Effects

Sodium calcium edetate is nephrotoxic and may cause renal tubular necrosis. Nausea, diarrhoea, and abdominal cramp may also occur. Thrombophlebitis has followed intravenous infusion and may be related to the concentration of the injection. Pain at the intramuscular injection site has been reported. Other adverse effects that have been reported include fever, malaise, headache, myalgia, histamine-like responses such as sneezing, nasal congestion, and lachrymation, skin eruptions, transient hypotension, and ECG abnormalities. Sodium calcium edetate chelates zinc within the body and zinc deficiency has been reported. Displacement of calcium from sodium calcium edetate may lead to hypercalcaemia.

Effects on the kidneys.

Of 130 children with lead poisoning who received chelation therapy with sodium calcium edetate (25 mg/kg intramuscularly every 12 hours) and dimercaprol (3 mg/kg intramuscularly every 4 hours) for a total of 5 days, 21 developed clinical evidence of nephrotoxicity and in 4 severe oliguric acute renal failure began 1 or 2 days after chelation therapy was discontinued.1 Nephrotoxicity was probably attributable to the use of sodium calcium edetate.
1. Moel DI, Kumar K. Reversible nephrotic reactions to a combined 2,3-dimercapto-l-propanol and calcium disodium ethylenediaminetetraacetic acid regimen in asymptomatic children with elevated blood lead levels. Pediatrics 1982; 70: 259–62.

💊 Precautions

Sodium calcium edetate should be used with caution, if at all, in patients with renal impairment. Daily urinalysis to monitor proteinuria and haematuria and regular monitoring of renal and hepatic function has been recommended. Sodium calcium edetate can chelate several endogenous metals, including zinc, and may increase their excretion; therapy should be intermittent to prevent severe deficiency developing and monitoring of zinc levels may be required (see below). Sodium calcium edetate should not be given orally in the treatment of lead poisoning as it has been suggested that absorption of lead may be increased as a result.
Blood-lead concentrations decreased to about 58% of the pretreatment values after 5 days and were essentially unchanged for up to 60 hours after the last dose. Sodium calcium edetate also produced a marked fall in the mean plasma-zinc concentration but this rebounded rapidly after the end of treatment. Mean urinary-lead excretion increased about 21-fold during the first 24 hours of therapy and urinary-zinc excretion increased about 17-fold. Sodium calcium edetate had little effect on the plasma concentrations or urinary excretion of copper. The results suggested that careful monitoring of zinc was required during treatment with sodium calcium edetate.
1. Thomas DJ, Chisolm JJ. Lead, zinc and copper decorporation during calcium disodium ethylenediamine tetraacetate treatment of lead-poisoned children. J Pharmacol Exp Ther 1986; 239: 829–35.

💊 Pharmacokinetics

Sodium calcium edetate is poorly absorbed from the gastrointestinal tract. It distributes primarily to the extracellular fluid and does not penetrate cells. It is not significantly metabolised; after intravenous injection about 50% of a dose is excreted in the urine in 1 hour and over 95% in 24 hours.

💊 Uses and Administration

Sodium calcium edetate is the calcium chelate of disodium edetate and is a chelator used in the treatment of lead poisoning. It mobilises lead from bone and tissues and aids elimination from the body by forming a stable, water-soluble, lead complex which is readily m n xHCl excreted by the kidneys. It may be used as a diagnostic test for lead poisoning but measurement of blood-lead concentrations is generally preferred. Sodium calcium edetate is also a chelator of other heavy-metal polyvalent ions, including chromium. A cream containing sodium calcium edetate 10% has been used in the treatment of chrome ulcers and skin sensitivity reactions due to contact with heavy metals. Sodium calcium edetate is also used as a pharmaceutical excipient and as a food additive. In the treatment of lead poisoning, sodium calcium edetate may be given by intramuscular injection or by intravenous infusion. The intramuscular route may be preferred in patients with lead encephalopathy and increased intracranial pressure in whom excess fluids must be avoided, and also in children, who have an increased risk of incipient encephalopathy. Sodium calcium edetate may initially aggravate the symptoms of lead toxicity due to mobilisation of stored lead and it has often been given with dimercaprol in patients who are symptomatic; the first dose of dimercaprol should preferably be given at least 4 hours before the sodium calcium edetate. For intravenous infusion, 1 g of sodium calcium edetate should be diluted with 250 to 500 mL of glucose 5% or sodium chloride 0.9%; a concentration of 3% should not be exceeded. The infusion should be given over a period of at least 1 hour. In the UK, the usual dose is 60 to 80 mg/kg daily given in two divided doses. In the USA, a dose of 1000 mg/m 2 daily is suggested for asymptomatic adults and children; a daily dose of 1500 mg/m 2 may be used in patients with symptomatic poisoning. Treatment is given for up to 5 days, repeated if necessary after an interval of at least 2 days. Any further treatment with sodium calcium edetate should then not be given for at least 7 days. Alternatively, the same daily dose of sodium calcium edetate may be given intramuscularly in 2 to 4 divided doses as a 20% solution. Intramuscular injection of sodium calcium edetate is painful and it is recommended that preservative-free procaine hydrochloride should be added to a concentration of 0.5 to 1.5% to minimise pain; alternatively, lidocaine may be added to a concentration of 0.5%. As excretion is mainly renal, an adequate urinary flow must be established and maintained during treatment. Doses should be reduced in patients with renal impairment (see below).

Administration in renal impairment.

The dose of sodium calcium edetate should be reduced in patients with renal impairment. It has been suggested that the dose is halved and given once daily in moderate impairment, and that smaller and less frequent doses are given if renal impairment is severe.

💊 Preparations

BP 2008: Sodium Calcium Edetate Intravenous Infusion; USP 31: Edetate Calcium Disodium Injection.

Proprietary Preparations

Ger.: Calcium Vitis†; Gr.: Ledclair; Irl.: Ledclair; Switz.: Chelintox†; Turk .: Libenta; UK: Ledclair. Multi-ingredient: Arg.: Calcium C.
Published December 23, 2018.