Edetate Calcium Disodium
Chemistry - A heavy metal chelating agent, edetate calcium disodium (CaEDTA ) occurs as an odorless, white, crystalline powder or granules and is a mixture of dihydrate and trihydrate forms. It has a slight saline taste and is slightly hygroscopic. CaEDTA is freely soluble in water and very slightly soluble in alcohol. The commercially available injection (human) has a pH of 6.5-8 and has approximately 5.3 mEq of sodium per gram of CaEDTA.
Edetate calcium disodium has several synonyms including: calcium disodium edathamil , Calcium EDTA (CaEDTA), calcium disodium edetate , calcium edetate , calcium disodium ethylenediaminetetra-acetate and sodium calcium edetate .
Storage/Stability/Compatibility - CaEDTA should be stored at temperatures less than 40°, and preferably at room temperature (15-30°C). The injection can be diluted with either normal saline or 5% dextrose.
Pharmacology - The calcium in CaEDTA can be displaced by divalent or trivalent metals to form a stable water soluble complex that can be excreted in the urine. One gram of CaEDTA can theoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted into the urine in lead poisoned patients. In addition to chelating lead, CaEDTA also chelates and eliminates zinc from the body. CaEDTA also binds cadmium, copper, iron and manganese, but to a much lesser extent than either lead or zinc. CaEDTA is relatively ineffective for use in treating mercury, gold or arsenic poisoning.
Uses/Indications - CaEDTA is used as a chelating agent in the treatment of lead poisoning.
Pharmacokinetics - CaEDTA is well absorbed after either IM or SQ administration. It is distributed primarily in the extracellular fluid. Unlike dimercaprol, CaEDTA does not penetrate erythrocytes or enter the CNS in appreciable amounts. The drug is rapidly excreted renally, either as unchanged drug or chelated with metals. Changes in urine pH or urine flow do not significantly alter the rate of excretion. Decreased renal function can cause accumulation of the drug and can increase its nephrotoxic potential. In humans with normal renal function, the average elimination half-life of CaEDTA is 20-60 minutes after IV administration, and 1.5 hours after IM administration.
Contraindications/Precautions/Reproductive Safety - CaEDTA is contraindicated in patients with anuria. It should be used with extreme caution and with dosage adjustment in patients with diminished renal function.
Most small animal clinicians recommend using the SQ route when treating small animals as IV administration of CaEDTA has been associated with abrupt increases in CSF pressure and death in children with lead-induced cerebral edema.
Adverse Effects/Warnings - The most serious of adverse effect associated with this compound is renal toxicity (renal tubular necrosis), but in dogs CaEDTA also can cause depression and GI symptoms. GI symptoms (vomiting, diarrhea) in dogs may be alleviated by zinc supplementation.
Do not administer CaEDTA orally as it may increase the amount of lead absorbed from the GI tract.
Animals with symptoms of cerebral edema should not be overhydrated.
Chronic therapy may lead to zinc deficiency; zinc supplementation should be considered in these animals.
Overdosage/Acute Toxicity - Doses greater than 12 g/kg are lethal in dogs; refer to Adverse Effects for more information.
Drug Interactions - Concurrent administration of CaEDTA with zinc insulin preparations (NPH, PZI) will decrease the sustained action of the insulin preparation.
The renal toxicity of CaEDTA may be enhanced by the concomitant administration of glucocorticoids. Use with caution with other nephrotoxic compounds (e.g., aminoglycosides, amphotericin B).
Drug/Laboratory Interactions - CaEDTA may cause increased urine glucose values and/or cause inverted T-waves on ECG.
The manufacturer of the injectable (human) product recommends diluting the injection to a concentration of 2 - 4 mg/ml with either normal saline or 5% dextrose when used for intravenous use. Because the injection is painful when given IM, 1 ml of procaine HCl 1% is recommended to be added to each ml of injection before administering IM.
For lead poisoning:
a) Remove animal from source of lead. If severely affected give CaEDTA at 75 mg/kg IV slowly in D5W or saline daily for 4-5 days (may divide daily dose into 2-3 administrations per day). Stop therapy for 2 days and repeat for another 4-5 days. Give adequate supportive and nutritional therapy. (Oehme 1987d)
Monitoring Parameters -
1) Blood lead or zinc (serial), and/or urine d-ALA
2) Renal function tests, urinalyses, hydration status
3) Serum phosphorus and calcium values
4) Periodic cardiac rate/rhythm monitoring may be warranted during administration
Client Information - Because of the potential toxicity of this agent and the seriousness of most heavy metal intoxications, this drug should be used with close professional supervision only.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Note: Do not confuse with Edetate Disodium which should not be used for lead poisoning as it may cause severe hypocalcemia.
Edetate Calcium Disodium Injection 50 mg/ml in 500 ml single dose vials. Meta-Dote® (Anthony) (Rx). Approved for use in cattle, horses, goats, sheep and swine. Not intended for use on animals to be used as food.
Edetate Calcium Disodium Injection 200 mg/ml in 5 ml amps (1 gram/amp); Calcium Disodium Versenate® (3M Pharm.) (Rx)
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