edetate calcium disodium (calcium EDTA)
Calcium Disodium Versenate

Available forms
Available by prescription only
Injection: 200 mg/ml

Indications and dosages
 Acute lead encephalopathy or blood lead levels above 70 mcg/dl. Adults and children: 1.5 g/m² I.V. or I.M. daily in divided doses q 12 hours for 3 to 5 days, usually with dimercaprol. Give second course in 5 to 7 days, if needed.
 Lead poisoning without encephalopathy or asymptomatic with blood levels below 70 mcg/dl. Children: 1 g/m² I.V. or I.M. daily in divided doses.
 Other heavy metal poisonings. ◇ Adults: 1 g in 500 ml of D₅W or normal saline injection infused I.V. over a 5-hour period once daily for 3 days.

Pharmacodynamics
Chelating action: Calcium in edetate calcium disodium is displaced by divalent and trivalent heavy metals and forms a soluble complex that is excreted in urine, thus removing the heavy metal.

Pharmacokinetics
Absorption: Well absorbed after I.M. or S.C. injection.
Distribution: Distributed primarily in extracellular fluid.
Metabolism: None.
Excretion: Excreted rapidly in urine. After I.V. administration, 50% of drug excreted in urine unchanged or as a metal chelate in 1 hour; 95% of drug excreted in 24 hours.

Contraindications and precautions
Contraindicated in patients with anuria, hepatitis, and acute renal disease. Use with extreme caution in patients with mild renal disease. Intracranial pressure may increase to dangerous levels with rapid I.V. administration.

Interactions
Drug-drug. Zinc insulin: Interferes with action of insulin by binding with zinc. Monitor glucose levels; insulin dosage may need adjustment.

Adverse reactions
CNS: tremor, headache, numbness, tingling, malaise, fatigue, fever.
CV: hypotension, cardiac rhythm irregularities, thrombophlebitis with I.V. administration.
GI: cheilosis, nausea, vomiting, anorexia, thirst.
GU: proteinuria, hematuria, nephrotoxicity with renal tubular necrosis leading to fatal nephrosis.
Hematologic: transient bone marrow depression.
Musculoskeletal: myalgia, arthralgia.
Skin: pain at I.M. injection site.
Other: chills.

Effects on lab test results
• May increase AST, ALT, and calcium levels.
• May decrease hemoglobin.

Overdose and treatment
Signs and symptoms of overdose include acute renal failure with anuria and altered consciousness consistent with increased intracranial pressure in patients with lead encephalopathy.
 Reduce intracranial pressure with hyperventilation and furosemide or mannitol; monitor vital signs and ECG closely. Barbiturate infusion may be needed in severe cases; hemodialysis may be needed in acute renal failure.

Special considerations
• Add 1% procaine or lidocaine to solution before I.M. injection to decrease pain at site.
• Avoid rapid I.V. infusion and infusions of large fluid volumes in patients with lead encephalopathy.
• Hydrate patients before giving drug to ensure adequate urine flow; monitor renal status frequently.
• Parenterally administered edetate calcium disodium has been used in poisoning by radioactive and nuclear fusion products and other heavy metals except mercury, gold, and arsenic poisoning. Drug has also been used to aid diagnosis of lead poisoning.
• For I.V. infusion, dilute drug with D₅W solution or normal saline solution; give one-half the daily dose over at least 1 hour in asymptomatic patients, 2 hours in symptomatic patients. The second daily infusion should be given 6 or more hours after the first. If administered as a single dose, infuse over 12 to 24 hours.
• If drug is given as a continuous I.V. infusion, interrupt infusion for at least 1 hour before a blood lead level reading to avoid a falsely elevated value.
• Thrombophlebitis may occur with I.V. administration if concentration exceeds 0.5% of EDTA.
• Monitor infusion site closely. Extravasation severely irritates tissue; rotate infusion sites with multiple doses or long-term therapy.
• Monitor calcium levels for hypercalcemia, and observe patient for seizures or altered vital signs and ECG during infusion. Administer infusion over at least 3 hours; have patient remain supine for 20 to 30 minutes after infusion because of possible orthostatic hypotension. Drug also exerts a negative inotropic effect on the heart.
• After I.V. administration, chelated lead appears in urine within 1 hour; excretion of lead peaks in 24 to 48 hours.
• Monitor hepatic and renal function before treatment and periodically throughout.
• Monitor intake and output, urinalysis, BUN level, and ECG throughout treatment; interrupt I.V. for 1 hour before drawing blood.
Pediatric patients
• I.M. route is recommended for children.

Patient education
• Explain measures as needed to avoid future heavy metal poisoning.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use