Edetate Calcium Disodium

Description

DESCRIPTION Edetate Calcium Disodium injection, USP is a sterile, injectable, chelating agent in concentrated solution for intravenous infusion or intramuscular injection. Each 5 mL single-dose vial contains 1,000 mg of edetate calcium disodium (equivalent to 200 mg/mL) in water for injection and sodium hydroxide (as pH adjuster). Chemically, this product is called [[N,N'-1,2-ethanediyl-bis[N-(carboxymethyl)-glycinato]](4-)-N,N',O,O',O N ,O N' ]-, disodium, hydrate, (OC-6-21)-Calciate(2-). Structural Formula: C 10 H 12 CaN 2 Na 2 O 8

What Is Edetate Calcium Disodium Used For?

INDICATIONS AND USAGE Edetate calcium disodium is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults. Chelation therapy should not replace effective measures to eliminate or reduce further exposure to lead.

Dosage and Administration

DOSAGE AND ADMINISTRATION When a source for the lead intoxication has been identified, the patient should be removed from the source, if possible. The recommended dose of edetate calcium disodium for asymptomatic adults and pediatric patients whose blood lead level is < 70 mcg/dL but > 20 mcg/dL (World Health Organization recommended upper allowable level) is 1,000 mg/m 2 /day whether given via intravenous infusion or intramuscularly (see Surface Area Nomogram). For adults with lead nephropathy, the following dosing regimen has been suggested: 500 mg/m 2 every 24 hours for 5 days for patients with serum creatinine levels of 2 to 3 mg/dL, every 48 hours for 3 doses for patients with creatinine levels of 3 to 4 mg/dL, and once weekly for patients with creatinine levels above 4 mg/dL. These regimens may be repeated at one month intervals. 12 Edetate calcium disodium, used alone, may aggravate symptoms in patients with very high blood lead levels. When the blood lead level is > 70 mcg/dL or clinical symptoms consistent with lead poisoning are present, it is recommended that edetate calcium disodium be used in conjunction with BAL (dimercaprol). Please consult published protocols and specialized references for dosage recommendations of combination therapy. 14-18 Therapy of lead poisoning in adults and pediatric patients with edetate calcium disodium is continued over a period of five days. Therapy is then interrupted for 2 to 4 days to allow redistribution of the lead and to prevent severe depletion of zinc and other essential metals. Two courses of treatment are usually employed; however, it depends on the severity of the lead toxicity and the patient's tolerance of the drug. Edetate calcium disodium is equally effective whether administered intravenously or intramuscularly. The intramuscular route is used for all patients with overt lead encephalopathy and this route is preferred by some for young pediatric patients. Acutely ill individuals may be dehydrated from vomiting. Since edetate calcium disodium is excreted almost exclusively in the urine, it is very important to establish urine flow with intravenous fluid administration before the first dose of the chelating agent is given; however, excessive fluid must be avoided in patients with encephalopathy. Once urine flow is established, further intravenous fluid is restricted to basal water and electrolyte requirements. Administration of edetate calcium disodium should be stopped whenever there is cessation of urine flow in order to avoid unduly high tissue levels of the drug. Edetate calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease. Intravenous Administration Add the total daily dose of edetate calcium disodium (1,000 mg/m 2 /day) to 250 to 500 mL of 5% dextrose or 0.9% sodium chloride injection. The total daily dose should be infused over a period of 8 to 12 hours. Discard unused portion. Edetate calcium disodium injection is incompatible with 10%...

Side Effects (Adverse Reactions)

ADVERSE REACTIONS The following adverse effects have been associated with the use of edetate calcium disodium: Body as a Whole: pain at intramuscular injection site, fever, chills, malaise, fatigue, myalgia, arthralgia. Cardiovascular: hypotension, cardiac rhythm irregularities. Renal: acute necrosis of proximal tubules (which may result in fatal nephrosis), infrequent changes in distal tubules and glomeruli. Urinary: glycosuria, proteinuria, microscopic hematuria and large epithelial cells in urinary sediment. Nervous System: tremors, headache, numbness, tingling. Gastrointestinal: cheilosis, nausea, vomiting, anorexia, excessive thirst. Hepatic: mild increases in SGOT and SGPT are common, and return to normal within 48 hours after cessation of therapy. Immunogenic: histamine-like reactions (sneezing, nasal congestion, lacrimation), rash. Hematopoietic: transient bone marrow depression, anemia. Metabolic: zinc deficiency, hypercalcemia. To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug Interactions

Drug Interactions There is no known drug interference with standard clinical laboratory tests. Steroids enhance the renal toxicity of edetate calcium disodium in animals. 7 Edetate calcium disodium interferes with the action of zinc insulin preparations by chelating the zinc. 7

Contraindications

CONTRAINDICATIONS Edetate calcium disodium should not be given during periods of anuria, nor to patients with active renal disease or hepatitis.

Pregnancy and Breastfeeding

Pregnancy One reproduction study was performed in rats at doses up to 13 times the human dose and revealed no evidence of impaired fertility or harm to the fetus due to edetate calcium disodium. 10 Another reproduction study performed in rats at doses up to about 25 to 40 times the human dose revealed evidence of fetal malformations due to edetate calcium disodium, which were prevented by simultaneous supplementation of dietary zinc. 11 There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when edetate calcium disodium is administered to a nursing woman.

Overdosage

OVERDOSAGE Symptoms Inadvertent administration of 5 times the recommended dose, infused intravenously over a 24 hour period, to an asymptomatic 16 month old patient with a blood lead content of 56 mcg/dL did not cause any ill effects. Edetate calcium disodium can aggravate the symptoms of severe lead poisoning, therefore, most toxic effects (cerebral edema, renal tubular necrosis) appear to be associated with lead poisoning. Because of cerebral edema, a therapeutic dose may be lethal to an adult or a pediatric patient with lead encephalopathy. Higher dosage of edetate calcium disodium may produce a more severe zinc deficiency. Treatment Cerebral edema should be treated with repeated doses of mannitol. Steroids enhance the renal toxicity of edetate calcium disodium in animals and, therefore, are no longer recommended. 7 Zinc levels must be monitored. Good urinary output must be maintained because diuresis will enhance drug elimination. It is not known if edetate calcium disodium is dialyzable.

How Supplied

HOW SUPPLIED Edetate Calcium Disodium injection, USP 5 mL single-dose vial (NDC 64980-588-05 ) containing 200 mg of edetate calcium disodium per mL (1,000 mg per vial), in boxes containing 5 vials (NDC 64980-588-51 ). Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].