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Edetate CALCIUM Disodium

Pronunciation

(ED e tate KAL see um dye SOW dee um)

Index Terms

  • CaEDTA
  • Calcium Disodium Edetate
  • Calcium Disodium EDTA
  • Calcium Disodiumethylenediaminetetraacetic Acid
  • Edetate Disodium CALCIUM
  • EDTA (CALCIUM Disodium) (error-prone abbreviation)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Generic: 500 mg/2.5 mL (2.5 mL [DSC]); 1 g/5 mL (5 mL)

Pharmacologic Category

  • Chelating Agent

Pharmacology

Calcium is displaced by divalent and trivalent heavy metals, forming a nonionizing soluble complex with lead that is excreted in the urine.

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

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 2-4 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: 1000 mg/m2/day or 25-50 mg/kg/day for 5 days; a maximum dose of 3000 mg has been suggested (Howland, 2011)

Lead encephalopathy (in conjunction with dimercaprol): Note: Begin treatment with edetate CALCIUM disodium with the second dimercaprol dose: IM, IV: 1500 mg/m2/day or 50-75 mg/kg/day for 5 days; a maximum dose of 3000 mg has been suggested (Howland, 2011)

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 2-3 mg/dL: 500 mg/m2 every 24 hours for 5 days

Scr 3-4 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: 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 2-4 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 or 50 mg/kg/day (maximum: 1000 mg/day) for 5 days (Chandran, 2010)

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: 1000 mg/m2/day or 25-50 mg/kg/day (maximum: 1000 mg/day) for 5 days (Chandran, 2010; Howland, 2011)

Lead encephalopathy (in conjunction with dimercaprol): Note: Begin treatment with edetate CALCIUM disodium with the second dimercaprol dose: IM, IV: 1500 mg/m2/day or 50-75 mg/kg/day (maximum: 1000 mg/day) for 5 days (Chandran, 2010; Howland, 2011)

Dosing: Renal Impairment

Dose should be reduced with pre-existing mild renal disease. Limiting the daily dose to 1 g in children and 2 g in adults may decrease risk of nephrotoxicity, although larger doses may be needed in the treatment of lead encephalopathy (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 8-12 hours or continuously over 24 hours (Howland, 2011)

For IM injection: Daily dose should be divided into 2-3 equal doses spaced 8-12 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.

Compatibility

Stable in D5W, NS; incompatible with D10W, LR, Ringer's injection.

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

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. Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Insulin: Edetate CALCIUM Disodium may enhance the hypoglycemic effect of Insulin. 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

ALERT: U.S. 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.

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: [U.S. 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 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, more thirst, headache, dry lips, muscle pain, joint pain, sneezing, rhinorrhea, tearing, or irritation at the injection site. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of high calcium (weakness, confusion, feeling tired, headache, nausea and vomiting, constipation, or bone pain), arrhythmia, tachycardia, 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 healthcare 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.

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