Calcium Disodium Versenate

Antidotes, Systemic
Chelating Agents

 
NOTE: Edetate calcium disodium (i.e., calcium EDTA) may aggravate symptoms associated with toxic lead levels in patients with blood lead levels > 70 mcg/dL. In these patients, calcium EDTA should be used in conjunction with dimercaprol. Patients may be severely dehydrated and urine flow should be established before the first dose is given, although excessive fluid intake should be avoided in patients with encephalopathy. The allowable upper limit of blood lead levels is 20 mcg/mL according to the World Health Organization.

Edetate calcium disodium is administered intramuscularly or intravenously.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

NOTE: Lethal increases in intracranial pressure have been reported in patients with lead encephalopathy and cerebral edema following intravenous administration. The intramuscular route is preferred for these patients. If the intravenous route is necessary, infuse slowly and monitor the patient carefully.
Dilute the total daily dose of edetate calcium disodium injection in 250—500 mL of 5% Dextrose injection or 0.9% Sodium Chloride injection to a final concentration of 2—4 mg/mL.
Intermittent infusion: Using an infusion pump, administer the diluted injection over 1 hour. NOTE: For the treatment of lead toxicity, the manufacturer recommends that the total daily dose be administered as a single infusion over 8—12 hours.
Continuous infusion: Infuse over 8—24 hours. The infusion should be interrupted for 1 hour before a blood lead concentration is measured to avoid a falsely elevated value.

Intramuscular injection is the preferred route of administration for patients at high risk for cerebral edema. Lethal increases in intracranial pressure have been reported in patients with lead encephalopathy and cerebral edema following the intravenous administration.
Intramuscular administration of calcium EDTA is painful. To minimize pain at the injection site, lidocaine or procaine may be added to edetate calcium disodium injection. A final lidocaine or procaine concentration of 0.5% (5 mg/mL) can be obtained as follows: 0.25 mL of 10% lidocaine solution per 5 mL of edetate calcium disodium; or 1 mL of 1% lidocaine or 1% procaine solution per ml of edetate calcium disodium.
Inject deeply into a well developed muscle. Aspirate prior to injection to avoid injection into a blood vessel. Massage injection site well following administration. Injection sites should be rotated.

anuria / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
oliguria / Early / Incidence not known
increased intracranial pressure / Early / Incidence not known

hematuria / Delayed / Incidence not known
glycosuria / Early / Incidence not known
hypotension / Rapid / Incidence not known
zinc deficiency / Delayed / Incidence not known
anemia / Delayed / Incidence not known
hypercalcemia / Delayed / Incidence not known

malaise / Early / Incidence not known
fatigue / Early / Incidence not known
chills / Rapid / Incidence not known
fever / Early / Incidence not known
myalgia / Early / Incidence not known
headache / Early / Incidence not known
tremor / Early / Incidence not known
polydipsia / Early / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
cheilitis / Delayed / Incidence not known
rash / Early / Incidence not known
sneezing / Early / Incidence not known
nasal congestion / Early / Incidence not known
lacrimation / Early / Incidence not known

Calcium disodium versenate (also known as edetate calcium disodium, calcium EDTA) is capable of producing toxic effects during the treatment of lead toxicity, and these effects can be fatal. Lead encephalopathy is relatively rare in adults, but occurs more often in children in whom it may be incipient and thus overlooked. The mortality rate in pediatric patients has been high. Intravenous administration of calcium EDTA can result in increased intracranial pressure and patients with lead encephalopathy and cerebral edema may experience a lethal increase in intracranial pressure following intravenous infusion. The intramuscular route is preferred for these patients. In cases where the intravenous route is necessary, avoid rapid infusion. The dosage schedule should be followed and at no time should the recommended daily dose be exceeded.

Calcium Disodium Versenate

Rx

Chelating agent; reduces blood concentrations and depot stores of lead.

500 mg/m2 IV (infused over 1 hour) or by IM injection. Urine is collected for 24 hours following administration of edetate calcium disodium. The mobilization test is considered positive if the ratio of mcg of lead excreted in urine to mg of calcium EDTA administered is greater than 1.

500 mg/m2 (Max: 1 g) IV over 1 hour, or by IM injection given as a single dose or 2 divided doses given 12 hours apart. Urine is collected for 24 hours following administration of edetate calcium disodium. If the ratio of mcg of lead excreted in urine to mg of calcium EDTA administered is greater than 1, the mobilization test is considered positive. Some experts recommend an 8-hour mobilization test using a single dose of 500 mg/m2 IV over 1 hour, or by IM injection. The test is positive if the ratio of mcg of lead excreted in urine to mg of calcium EDTA administered is greater than 0.5 to 0.6. Alternatively, a dose of 50 mg/kg (Max: 1 g) IM may be administered, with urine collected for 6 to 8 hours following administration of the dose. If the ratio of mcg of lead excreted in urine to mg of calcium EDTA administered is greater than 0.5 or urine lead concentration is greater than 1 mg/L, the test is considered positive.

NOTE: Lead encephalopathy occurs more frequently in children than adults. Lethal increases in intracranial pressure have been reported in patients with lead encephalopathy and cerebral edema following the intravenous administration of edetate calcium disodium. The intramuscular route is preferred for these patients. However, intramuscular administration is painful at the site of injection. If the intravenous route is necessary, infuse slowly and monitor the patient carefully. Do not exceed the recommended dose.

The first dose of edetate calcium disodium should be given 4 or more hours after the initial dimercaprol injection, when urine flow has been established. Administer calcium EDTA 1,500 mg/m2 as an IV infusion, preferably over 12 to 24 hours, in combination with IM dimercaprol. If fluid restriction is desired (e.g., patients with encephalopathy or cerebral edema), the total dose can be given IM in equally divided doses at 8 to 12 hour intervals. Continue with calcium EDTA 1,500 mg/m2/day for 5 days, in combination with dimercaprol for at least the first 3 days of therapy. A second 5-day course of therapy (after at least 2 days without treatment) is recommended in patients with severe poisoning. Patients with a residual blood lead concentration greater than 70 mcg/dL should receive combined therapy with calcium EDTA plus dimercaprol. Patients with residual concentrations of 45 to 69 mcg/dL should receive calcium EDTA alone. A third course of therapy with calcium EDTA alone is required only if blood lead concentration rebounds to greater than 45 mcg/dL within 48 hours after the second treatment course. Wait at least 5 to 7 days before beginning a third course (if indicated), unless clinical status dictates earlier treatment.

The calcium EDTA dosage is 1,000 mg/m2/day by IV infusion, administered over 8 to 24 hours (NOTE: The American Academy of Pediatrics suggests that therapy with oral succimer is preferred in patients with blood lead concentrations of 45 to 69 mcg/dL who do not have symptoms of lead encephalopathy). An alternative calcium EDTA regimen is 25 mg/kg/day by IV infusion over 8 to 24 hours. Therapy is generally continued for 5 days. Although the IV route is preferred, calcium EDTA may also be given IM in divided doses at 8 to 12 hour intervals. A second course of therapy may be required if the blood lead concentration rebounds to 45 mcg/dL or higher within 7 to 14 days after treatment. Allow 5 to 7 days without treatment before beginning a second course of calcium EDTA.

1 g/m2/day IV over 8 to 24 hours (or by IM injection) for 5 days. May repeat monthly until lead excretion is reduced toward normal.

500 mg/m2/day IV over 8 to 24 hours (or by IM injection) for 5 days. May repeat monthly until lead excretion is reduced toward normal.

500 mg/m2 IV over 8 to 24 hours (or by IM injection), given every 48 hours for 3 doses. May repeat monthly until lead excretion is reduced toward normal.

500 mg/m2 IV over 8 to 24 hours (or by IM injection), given once per week. May repeat monthly until lead excretion is reduced toward normal.

Specific dosage guidelines have not been established; however calcium EDTA is contraindicated in patients with hepatitis.

Specific dosage guidelines have not been established; however, dosage guidelines based on serum creatinine have been suggested for patients with lead nephropathy. These guidelines may also be useful for patients with preexisting renal impairment. The manufacturer states that edetate calcium disodium is contraindicated in patients with active renal disease.

Calcium Acetate: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium Carbonate: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium Carbonate; Magnesium Hydroxide: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium Carbonate; Simethicone: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium Chloride: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium Gluconate: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Calcium; Vitamin D: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Cardiac glycosides: (Major) The pharmacodynamic actions of edetate disodium oppose those of the cardiac glycosides.
Chlorpheniramine; Pseudoephedrine: (Major) Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.
Chromium: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Digoxin: (Major) The pharmacodynamic actions of edetate disodium oppose those of the cardiac glycosides.
Folic Acid, Vitamin B9: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Insulins: (Minor) Use caution in administration of calcium EDTA to patients with diabetes mellitus who are receiving insulin therapy. Calcium EDTA chelates the zinc in selected exogenous insulins, thereby increasing the amount of insulin available to the body and decreasing the duration of the insulin dose. Alterations in blood glucose control may result. Diabetic patients receiving calcium EDTA may require adjustments in their insulin dosage.
Magnesium Citrate: (Major) Administration of oral magnesium citrate with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA.
Magnesium Salts: (Major) Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA.
Magnesium: (Major) Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA.
Pyridoxine, Vitamin B6: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Major) Administration of oral magnesium with edetate disodium, disodium EDTA may result in binding of magnesium. Do not administer oral magnesium salts within 1 hour of edetate disodium, EDTA.
Succimer: (Moderate) Concomitant use of succimer and other chelation therapy such as edetate calcium disodium, calcium EDTA (CaNa2EDTA) with or without dimercaprol (BAL) is not recommended, as data are not available. Patients who have received CaNa2EDTA with or without dimercaprol may use succimer for subsequent treatment after an interval of 4 weeks.
Zinc Salts: (Major) Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.
Zinc: (Major) Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.

Calcium Disodium Versenate/Edetate Calcium Disodium Intramuscular Inj Sol: 1mL, 200mg
Calcium Disodium Versenate/Edetate Calcium Disodium Intravenous Inj Sol: 1mL, 200mg

1500 mg/m2/day IV or IM.

1500 mg/m2/day IV or IM.

1500 mg/m2/day IV or IM.

1500 mg/m2/day IV or IM.

1500 mg/m2/day IV or IM.

Calcium EDTA is a chelating agent with an affinity for divalent and trivalent metals. Once administered, the calcium component of calcium EDTA can be displaced by other divalent and trivalent metals, forming stable, soluble complexes that are then excreted by the kidneys. EDTA has a greater affinity for lead than for calcium and releases calcium to bind with lead. The noncalcium-containing formulation of EDTA should not be used to treat lead toxicity because it will preferentially bind calcium, and serious hypocalcemia can result.
 
One gram of edetate calcium disodium has the potential to combine with 620 mg of lead. Typically, however, only 3—5 mg of lead are excreted in response to a 1 g dose of the drug when administered to patients with acute lead poisoning or high levels of lead in the soft tissues.
 
Once calcium EDTA is circulating in the bloodstream and extracellular fluids, it can increase the urinary excretion of lead, but orally administered dosages of the drug increase the absorption of lead. Therefore, calcium EDTA is only administered subcutaneously, intravenously, or intramuscularly. The excretion of zinc is greatly increased following administration of calcium EDTA, and although mercury will displace calcium from its binding site on calcium EDTA, the drug is not effective in treating mercury poisoning, perhaps because mercury is too tightly bound to the ligands of the tissues or is sequestered in compartments of the body that calcium EDTA does not penetrate. Calcium EDTA is also not effective in the treatment of gold or arsenic poisoning.

Calcium EDTA is administered intravenously or intramuscularly. The drug distributes predominantly into the extracellular fluid and does not enter erythrocytes or the CNS to a significant extent. Calcium EDTA is not metabolized and is excreted primarily by the kidneys, with 50% excreted in 1 hour and 95% within 24 hours. The half-life is 20 to 60 minutes.
 
Affected cytochrome P450 isoenzymes: none

Calcium EDTA is rapidly absorbed following intravenous administration.

Calcium EDTA is rapidly absorbed following intramuscular administration.

Calcium EDTA is classified as FDA pregnancy risk category B. No adequate human studies have examined the effects of this drug on the human fetus; however, animal studies have revealed no adverse fetal or reproductive effects. Consider the benefits of the drug to the mother, the potential risks to the fetus, and the potential adverse effects to both resulting from untreated lead poisoning. The manufacturer advises use during pregnancy only if clearly needed.

Advise patients requiring calcium EDTA for treatment of lead poisoning to avoid breast-feeding; lead is excreted in breast milk and is toxic to nursing infants. Data are limited regarding use of calcium EDTA in lactating women and its excretion in human milk is unknown. Although the drugs low molecular weight (374) suggests excretion in breast milk, its short half-life (20—60 minutes) and poor oral bioavailability may limit the potential exposure in a nursing infant.