EDETATE CALCIUM DISODIUM, CALCIUM EDTA

Chemistry - A heavy metal chelating agent, edetate calcium disodium (CaEDTA) occurs as anodorless, white, crystalline powder or granules and is a mixture of dihydrate and trihydrate forms. Ithas a slight saline taste and is slightly hygroscopic. CaEDTA is freely soluble in water and veryslightly soluble in alcohol. The commercially available injection (human) has a pH of 6.5-8 and hasapproximately 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 disodiumethylenediaminetetra-acetate and sodium calcium edetate.

Storage, Stability, Compatibility

CaEDTA should be stored at temperatures less than 40°, andpreferably at room temperature (15-30°C). The injection can be diluted with either normal saline or5% dextrose.

Pharmacology - EDETATE CALCIUM DISODIUM, CALCIUM EDTA

The calcium in CaEDTA can be displaced by divalent or trivalent metals to form astable water soluble complex that can be excreted in the urine. One gram of CaEDTA cantheoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted intothe urine in lead poisoned patients. In addition to chelating lead, CaEDTA also chelates andeliminates zinc from the body. CaEDTA also binds cadmium, copper, iron and manganese, but to amuch lesser extent than either lead or zinc. CaEDTA is relatively ineffective for use in treatingmercury, gold or arsenic poisoning.
Uses, Indications - CaEDTA is used as a chelating agent in the treatment of lead poisoning.

Pharmacokinetics - EDETATE CALCIUM DISODIUM, CALCIUM EDTA

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 patientswith anuria. It should be used with extreme caution and with dosage adjustment in patients withdiminished renal function.
Most small animal clinicians recommend using the SQ route when treating small animals as IVadministration of CaEDTA has been associated with abrupt increases in CSF pressure and death inchildren with lead-induced cerebral edema.

Adverse Effects, Warnings

The most serious of adverse effect associated with this compound isrenal toxicity (renal tubular necrosis), but in dogs CaEDTA also can cause depression and GIsymptoms. 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 GItract.
Animals with symptoms of cerebral edema should not be overhydrated.
Chronic therapy may lead to zinc deficiency; zinc supplementation should be considered in theseanimals.

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.