Edetate Calcium Disodium (Calcium EDTA, or sodium calcium edetate) is a chelating agent that is used for the short-term and long-term management of patients with acute and chronic lead poisoning.

Indications of Edetate Calcium Disodium (Calcium EDTA):

• It is indicated for the treatment of acute and chronic lead poisoning.

Edetate calcium disodium dose in Adults

Edetate calcium disodium dose in adults for the treatment of Lead poisoning:

Note:

• The standard recommendation is 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.
• Additional therapy depends upon blood level; at least 2 to 4 days should elapse before a 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: start its administration with the second dimercaprol dose:

• • IM, IV: 1,000 mg/m²/day OR 25 to 50 mg/kg/day for 5 days.
  • The maximum dose: 3,000 mg.

• Lead encephalopathy (in conjunction with dimercaprol):

Note: Start  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 recommended.

• 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:
    • S. Creatinine of 2 to 3 mg/dL: 500 mg/m² every 24 hours for 5 days
    • S. Creatinine of 3 to 4 mg/dL: 500 mg/m² every 48 hours for 3 doses
    • S. Creatinine of >4 mg/dL: 500 mg/m² once a week

Edetate calcium disodium dose in Childrens

Edetate Calcium Disodium (Calcium EDTA) Dose in the treatment of Lead poisoning:

• Infants, Children, and Adolescents:

Note:

• For the treatment of high-grade lead poisoning in children, the CDC recommends chelation treatment when blood lead levels are >45 mcg/dL.
• 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. 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.
• Additional dosing depends upon blood lead level; at least 2 to 4 days should elapse before a 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.

  • 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.

  • 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.

Pregnancy Risk Factor B

• Some adverse events were seen in animal reproduction studies.
• However, there are not well-controlled studies on edetate CALCIUM diodium in pregnant women.
• It can also cross the placental barrier due to the maternal plasma level.
• Exposure to it during pregnancy can result in spontaneous abortion, preterm birth, reduced birth weight, impaired neurodevelopment, and even preterm delivery.
• High maternal lead levels of 10 mg/dL can cause severe side effects.
• Pregnant women who are exposed to lead might be at greater risk for gestational hypertension.
• Pregnant women who have blood lead levels greater than 45 mcg/dL should consider chelation therapy.
• However, pregnant women with blood lead levels higher than 70 mcg/dL should also be considered for chelation, regardless of trimester.
• Other options to edetate CALCIUM diodium might be recommended. Consultation with experts in lead poisoning or high-risk pregnancies is highly recommended.
• It doesn't matter what trimester, pregnant women with encephalopathy should be treated.

Edetate calcium disodium use during breastfeeding:

• Low oral absorption of edetate CALCIUM diodium (5%), which could limit exposure for nursing infants.
• Oral administration of Edetate Calcium Disodium may increase lead absorption. Therefore, oral use is not recommended.
• Breast milk lead concentrations can range from 0.6% to 3.3% of maternal serum concentrations
• If your blood lead level is >40 mg/dl, breastfeeding is not recommended until it reaches 40 mg/dl.
• Supplements containing calcium can also lower lead levels in breastmilk.

Edetate Calcium Disodium (Calcium EDTA) Dose in Kidney Disease:

• The dose should be reduced with preexisting mild renal disease.
• Limiting the daily dose to 2 gms in adults may decrease the risk of nephrotoxicity, although larger doses may be needed in the treatment of lead encephalopathy. 

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Edetate Calcium Disodium (Calcium EDTA):

• 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

Contraindications to Edetate Calcium Disodium (Calcium EDTA):

• Anuria or active renal disease
• Hepatitis

Warnings and precautions

• Arrhythmias:

  • During IV therapy, monitor for ECG changes and arrhythmias.

• Nephrotoxicity:

  • Potentially nephrotoxic, Edetate CALCIUM diodium may cause renal damage. High doses can cause renal tubular acidosis or fatal nephrosis.
  • Stop using therapy if you experience anuria, increased proteinuria or hematuria.
  • You can minimize nephrotoxicity through adequate hydration, good urine output, and avoiding excessive doses. Also, limit continuous administration to 5 days.

• Cerebral edema [US Boxed Warning]

  • Patients with cerebral edema or lead encephalopathy should be treated with caution.
  • Infusions of IV fluid to patients with cerebral edema can cause intracranial pressure to rise, so intramuscular administration is recommended.

• Lead poisoning:

  • To treat lead poisoning one must first identify the source and then remove it.
  • Before recommending chelation drug therapy, primary care providers should consult specialists in the treatment of lead poisoning.
  • Patients should not be allowed to return to the contaminated environment without having been treated for lead.

• Renal impairment

  • Patients with renal impairments will require dose adjustment.

Edetate calcium disodium (calcium EDTA): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Urinary output;
• urinalysis;
• renal function,
• hepatic function,
• serum electrolytes at baseline and daily in severe lead poisoning or at days 2 and 5 in patients with less severe lead poisoning;
• ECG when the drug is administered intravenously;
• 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

How to administer Edetate Calcium Disodium (Calcium EDTA)?

• It should be administered IM or IV only; the IV route is generally preferred, however,  If cerebral edema is there inject intramuscularly.

IV infusion:

• Administer the daily dose as a diluted solution over 8 to 12 hours or continuously over 24 hours.

For IM injection:

• The 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 the injection site.
• Administer by deep IM injection. When used in conjunction with dimercaprol, inject into a separate site.

Mechanism of action of Edetate Calcium Disodium (Calcium EDTA):

• The drug's calcium is replaced with divalent or trivalent metals.
• This forms non-ionizing, soluble complexes that are excreted by the urine.

The beginning of action: Chelation of Lead:

• IV: 1 hour
• Maximum excretion of chelated Lead with IV Administration: 24-48 hours

Absorption:

• IM, SubQ: Well absorbed;
• Oral: <5%

Distribution:

• Into extracellular fluid;
• minimal cerebrospinal fluid penetration (~5%)

Metabolism:

• Almost none of the drug is metabolized

Half-life elimination:

• 20 to 60 minutes

Excretion:

• Urine (as metal chelates or unchanged drug); decreased GFR decreases elimination

International Brand Names of Edetate calcium disodium:

• Calcium Edetate de Sodium
• Edetal-CA
• Kedato

Edetate calcium disodium Brand Names in Pakistan:

No Brands Available in Pakistan.