WARNINGS
See BOX WARNING.
PRECAUTIONS
General Precautions: Edetate calcium disodium may produce the same renal damage as lead poisoning, such as proteinuria and microscopic hematuria. Treatment-induced nephrotoxicity is dose-dependent and may be reduced by assuring adequate diuresis before therapy begins. Urine flow must be monitored throughout therapy which must be stopped if anuria or severe oliguria develop. The proximal tubule hydropic degeneration usually recovers upon cessation of therapy. Edetate calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease.
Patients should be monitored for cardiac rhythm irregularities and other ECG changes during intravenous therapy.
Information for patients: Patients should be instructed to immediately inform their physician if urine output stops for a period of 12 hours. Laboratory tests: Urinalysis and urine sediment, renal and hepatic function and serum electrolyte levels should be checked before each course of therapy and then be monitored daily during therapy in severe cases, and in less serious cases after the second and fifth day of therapy. Therapy must be discontinued at the first sign of renal toxicity. The presence of large renal epithelial cells or increasing number of red blood cells in urinary sediment or greater proteinuria call for immediate stopping of edetate calcium disodium administration. Alkaline phosphatase values are frequently depressed (possibly due to decreased serum zinc levels), but return to normal within 48 hours after cessation of therapy. Elevated erythrocyte protoporphyrin levels (>35 mcg/dl of whole blood) indicate the need to perform a venous blood lead determination. If the whole blood lead concentration is between 25-55 mcg/dl a mobilization test can be considered. 7,8(See Diagnostic Test.) An elevation of urinary coproporphyrin (adults: >250 mcg/day; pediatric patients under 80 lbs: >75 mcg/day) and elevation of urinary delta aminolevulinic acid (ALA) (adults: >4 mg/day; pediatric patients: >3 mg/m2/day) are associated with blood lead levels >40 mcg/dl. Urinary coproporphyrin may be falsely negative in terminal patients and in severely iron-depleted pediatric patients who are not regenerating heme.9 In growing pediatric patients long bone x-rays showing lead lines and abdominal x-rays showing radio-opaque material in the abdomen may be of help in estimating the level of exposure to lead.
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 Carcinogenesis, Mutagenesis, Impairment of Fertility: Long term animal studies have not been conducted with edetate calcium disodium to evaluate its carcinogenic potential, mutagenic potential or its effect on fertility.
Pregnancy: Category B: 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 Calcium Disodium Versenate. 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 Calcium Disodium Versenate, 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. Labor and Delivery: Calcium Disodium Versenate has no recognized use during labor and delivery, and its effects during these processes are unknown. 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 Calcium Disodium Versenate is administered to a nursing woman. Pediatric Use: Since lead poisoning occurs in pediatric populations and adults but is frequently more severe in pediatric patients, Calcium Disodium Versenate is used in patients of all ages. The intramuscular route is preferred by some for young pediatric patients. In cases where the intravenous route is necessary, avoid rapid infusion. (See WARNINGS.) Urine flow must be monitored throughout therapy; Calcium Disodium Versenate therapy must be stopped if anuria or severe oliguria develops. (See General Precautions.) At no time should the recommended daily dosage be exceeded. (See DOSAGE AND ADMINISTRATION.)
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