Boxed Warning
Cerebral edema:
Edetate calcium disodium is capable of producing toxic effects that can be fatal. Lead encephalopathy is relatively rare in adults, but occurs more often in pediatric patients in whom it may be incipient and thus overlooked. The mortality rate in pediatric patients has been high. Patients with lead encephalopathy and cerebral edema may experience a lethal increase in intracranial pressure following, intravenous (IV) infusion; the intramuscular (IM) route is preferred for these patients. In cases where the IV route is necessary, avoid rapid infusion. The dosage schedule should be followed and at no time should the recommended daily dose be exceeded.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Generic: 1 g/5 mL (5 mL)
Pharmacology
Mechanism of Action
Calcium is displaced by divalent and trivalent heavy metals, forming a nonionizing soluble complex with lead that is excreted in the urine.
Pharmacokinetics/Pharmacodynamics
Absorption
IM, SubQ: Well absorbed; Oral: <5%
Distribution
Into extracellular fluid; minimal CSF penetration (~5%)
Metabolism
Almost none of the drug is metabolized
Excretion
Urine (as metal chelates or unchanged drug); decreased GFR decreases elimination
Onset of Action
Chelation of lead: IV: 1 hour; Maximum excretion of chelated lead with IV administration: 24 to 48 hours
Half-Life Elimination
20-60 minutes
Use: Labeled Indications
Treatment of symptomatic acute and chronic lead poisoning
Contraindications
Active renal disease or anuria; hepatitis
Dosage and Administration
Dosing: Adult
Lead poisoning: Note: Available guidelines recommend chelation therapy with blood lead levels >50 mcg/dL and significant symptoms; chelation therapy may also be indicated with blood lead levels ≥100 mcg/dL and/or symptoms (Kosnett 2007). Depending upon the blood lead level, additional courses may be necessary; at least 2 to 4 days should elapse before repeat treatment is initiated.
Blood lead levels <70 mcg/dL and asymptomatic: IM, IV: 1000 mg/m2/day for 5 days
Blood lead levels ≥70 mcg/dL or symptomatic lead poisoning (in conjunction with dimercaprol): Note: Begin treatment with edetate CALCIUM disodium with the second dimercaprol dose: IM, IV: 1,000 mg/m2/day or 25 to 50 mg/kg/day for 5 days; a maximum dose of 3,000 mg has been suggested (Howland 2015)
Lead encephalopathy (in conjunction with dimercaprol): Note: Begin treatment with edetate CALCIUM disodium with the second dimercaprol dose: IM, IV: 1,500 mg/m2/day or 50 to 75 mg/kg/day for 5 days; a maximum dose of 3,000 mg has been suggested (Howland 2015)
Lead nephropathy: An alternative dosing regimen reflecting the reduction in renal clearance is based upon the serum creatinine; Note: Repeat regimen monthly until lead levels are reduced to an acceptable level: IM, IV:
Scr 2 to 3 mg/dL: 500 mg/m2 every 24 hours for 5 days
Scr 3 to 4 mg/dL: 500 mg/m2 every 48 hours for 3 doses
Scr >4 mg/dL: 500 mg/m2 once weekly
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Lead poisoning, treatment: Infants, Children, and Adolescents: Note: For the treatment of high blood lead levels in children, the CDC recommends chelation treatment when blood lead levels are >45 mcg/dL (CDC 2002). The AAP recommends succimer as the drug used for initial management in asymptomatic children when blood lead levels are >45 mcg/dL and <70 mcg/dL. Edetate CALCIUM disodium can be used in children allergic to succimer (AAP 2005; Chandran 2010). Combination therapy with edetate CALCIUM disodium and dimercaprol is recommended for use in children whose blood lead levels are ≥70 mcg/dL or in children with lead encephalopathy (AAP 2005; Chandran 2010). Depending upon the blood lead level, additional courses may be necessary; at least 2 to 4 days should elapse before repeat treatment is initiated.
Blood lead levels <70 mcg/dL and asymptomatic: IM, IV: 1,000 mg/m2/day for 5 days or 50 mg/kg/day for 5 days with a suggested maximum daily dose of 1,000 mg/day in children or 2,000 mg/day in adults (Chandran 2010; Howland 2011)
Blood lead levels ≥70 mcg/dL or symptomatic lead poisoning (in conjunction with dimercaprol): Note: Begin treatment with edetate CALCIUM disodium with the second dimercaprol dose: IM, IV: 1,000 mg/m2/day or 25 to 50 mg/kg/day for 5 days with a suggested maximum daily dose of 1,000 mg/day in children or 2,000 to 3,000 mg/day in adults (Chandran 2010; Howland 2011)
Lead encephalopathy (in conjunction with dimercaprol): Note: Begin treatment with edetate CALCIUM disodium with the second dimercaprol dose: IM, IV: 1,500 mg/m2/day or 50 to 75 mg/kg/day for 5 days with a suggested (maximum daily dose of : 1,000 mg/day in children or 2,000 to 3,000 mg in adults) (Chandran 2010; Howland 2011)
Reconstitution
For IV infusion, dilute total daily dose into 250-500 mL of 0.9% sodium chloride or D5W. Concentrations >0.5% (5 mg/mL) should be avoided. Procaine or lidocaine may be added to solutions given by IM injection.
Administration
For IM or IV use; IV is generally preferred, however, the IM route is preferred when cerebral edema is present.
IV infusion: Administer the daily dose as a diluted solution over 8 to 12 hours or continuously over 24 hours (Howland 2015)
For IM injection: Daily dose should be divided into 2 to 3 equal doses spaced 8 to 12 hours apart. Procaine hydrochloride or lidocaine may be added to the edetate CALCIUM disodium to minimize pain at injection site. Administer by deep IM injection. When used in conjunction with dimercaprol, inject into a separate site.
Storage
Store at 25°C (77°F); excursion permitted to 15°C to 30°C (59°F to 86°F).
Drug Interactions
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Insulins: Edetate CALCIUM Disodium may enhance the hypoglycemic effect of Insulins. Monitor therapy
Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Test Interactions
If edetate CALCIUM disodium is given as a continuous IV infusion, stop the infusion for at least 1 hour before blood is drawn for lead concentration to avoid a falsely elevated value
Adverse Reactions
Frequency not defined.
Cardiovascular: Cardiac arrhythmia, ECG changes, hypotension, local thrombophlebitis (IV infusion when concentration >5 mg/mL)
Central nervous system: Chills, fatigue, headache, malaise, numbness, paresthesia
Dermatologic: Cheilosis, dermatitis, skin rash
Endocrine & metabolic: Glycosuria, hypercalcemia, hypokalemia, iron deficiency (with chronic therapy), magnesium deficiency (with chronic therapy), polydipsia, zinc deficiency (with chronic therapy)
Gastrointestinal: Anorexia, gastrointestinal irritation, nausea, vomiting
Genitourinary: Nephrosis, nephrotoxicity, occult blood in urine, proteinuria, urinary frequency, urinary urgency
Hematologic & oncologic: Anemia, bone marrow depression (transient)
Hepatic: Decreased serum alkaline phosphatase, increased liver enzymes (mild)
Local: Pain at injection site (intramuscular)
Neuromuscular & skeletal: Arthralgia, myalgia, tremor
Ophthalmic: Lacrimation
Renal: Renal tubular necrosis
Respiratory: Nasal congestion, sneezing
Miscellaneous: Fever
Warnings/Precautions
Concerns related to adverse effects:
- Arrhythmias: Monitor for arrhythmias and ECG changes during IV therapy
- Nephrotoxicity: Edetate CALCIUM disodium is potentially nephrotoxic. Renal tubular acidosis and fatal nephrosis may occur, especially with high doses; do not exceed the recommended daily dose. If anuria, increasing proteinuria, or hematuria occurs during therapy, discontinue use. Minimize nephrotoxicity by providing adequate hydration, establishment of good urine output, avoidance of excessive doses, and limit continuous administration to ≤5 days.
Disease-related concerns:
- Cerebral edema: [US Boxed Warning]: Use with extreme caution in patients with lead encephalopathy and cerebral edema. In these patients, IV infusion has been associated with a lethal increase in intracranial pressure; IM injection is preferred.
- Lead poisoning: Investigate, identify, and remove sources of lead exposure prior to treatment. Primary care providers should consult experts in chemotherapy of lead toxicity before using chelation drug therapy. Do not permit patients to re-enter the contaminated environment until lead abatement has been completed.
- Renal impairment: Use with caution in patients with renal impairment; reduced dose recommended.
Other warnings/precautions:
- Potential for name confusion: Exercise caution in the ordering, dispensing, and administration of this drug. Edetate CALCIUM disodium (CaEDTA) may be confused with edetate disodium (Na2EDTA) (not commercially available in the US or Canada). Fatal hypocalcemia may result if edetate disodium is used for the treatment of lead poisoning instead of edetate CALCIUM disodium (Baxter 2008). The CDC and FDA recommend that edetate disodium should never be used for chelation therapy (especially in children) (Mitka 2008). Death has occurred following the use of edetate disodium for chelation therapy in pediatric patients with autism (Baxter 2008).
Monitoring Parameters
Urinary output; urinalysis; renal function, hepatic function, serum electrolytes (baseline and daily [severe lead poisoning] or at days 2 and 5 [less severe lead poisoning]); ECG (with IV therapy); blood lead levels (baseline and 7-21 days after completing chelation therapy); hemoglobin or hematocrit; iron status; free erythrocyte protoporphyrin or zinc protoporphyrin; neurodevelopmental changes
Pregnancy
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies; there are no well controlled studies of edetate CALCIUM disodium in pregnant women. Lead is known to cross the placenta in amounts related to maternal plasma levels. Prenatal lead exposure may be associated with adverse events such as spontaneous abortion, preterm delivery, decreased birth weight, and impaired neurodevelopment. Some adverse outcomes may occur with maternal blood lead levels <10 mcg/dL. In addition, pregnant women exposed to lead may have an increased risk of gestational hypertension. Consider chelation therapy in pregnant women with confirmed blood lead levels ≥45 mcg/dL (pregnant women with blood lead levels ≥70 mcg/dL should be considered for chelation regardless of trimester). Alternatives to edetate CALCIUM disodium may be indicated and consultation with experts in lead poisoning and high-risk pregnancy is recommended. Encephalopathic pregnant women should be chelated regardless of trimester (CDC 2010).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, lack of appetite, increased thirst, headache, dry lips, muscle pain, joint pain, sneezing, runny nose, tearing, or irritation at the injection site. Have patient report immediately to prescriber signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of high calcium (weakness, confusion, fatigue, headache, nausea and vomiting, constipation, or bone pain), abnormal heartbeat, fast heartbeat, loss of strength and energy, severe dizziness, passing out, tremors, numbness, or tingling (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
