Edetate calcium disodium

Mechanism of Action

Chelating agent to enhance elimination of metals, particulary lead

Agent being chelated takes place of Ca++

You should not receive edetate calcium disodium if you are allergic to it, or if you have:

• active hepatitis;

• active kidney disease; or

• if you are unable to urinate.

If possible before you receive edetate calcium disodium, tell your doctor if you have liver or kidney disease.

FDA pregnancy category B. Edetate calcium disodium is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether edetate calcium disodium passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

In an emergency situation it may not be possible to tell your caregivers if you are pregnant or breast feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medicine.

Because you will receive edetate calcium disodium in a clinical setting, you are not likely to miss a dose.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

• little or no urinating;

• a light-headed feeling, like you might pass out;

• numbness or tingly feeling;

• pink or red urine;

• feeling very thirsty; or

• fever, chills, pale skin, easy bruising.

Edetate calcium disodium can have toxic effects in the body, which may cause life-threatening medical problems. Call your doctor at once if you have memory problems, mood changes, trouble concentrating, changes in behavior or mental status, or if you feel irritable.

Common side effects may include:

• pain where the medicine was injected;

• fever, chills, general ill feeling, tired feeling;

• muscle or joint pain;

• headache, tremors;

• nausea, vomiting, loss of appetite;

• sneezing, stuffy nose, watery eyes; or

• mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Lead Poisoning -- Mild:

For asymptomatic adult patients whose blood lead level is < 70 mcg/dL but > 20 mcg/dL (World Health Organization recommended upper allowable level):

1000 mg/m2/day given intravenously or intramuscularly

Therapy of lead poisoning in adult patients with edetate calcium disodium is continued over a period of five days. Therapy is then interrupted for 2 to 4 days to allow redistribution of the lead and to prevent severe depletion of zinc and other essential metals. Two courses of treatment are usually employed; however, it depends on severity of the lead toxicity and the patient's tolerance of the drug.

Edetate calcium disodium is equally effective whether administered intravenously or intramuscularly. The intramuscular route is used for all patients with overt lead encephalopathy.

Usual Adult Dose for Lead Poisoning -- Severe:

When the blood lead level is > 70 mcg/dL or clinical symptoms consistent with lead poisoning are present, it is recommended that edetate calcium disodium be used in conjunction with BAL (dimercaprol). Clinician should consult latest published protocols and/or a local poison control information center for dosing.

Usual Pediatric Dose for Lead Poisoning -- Mild:

For asymptomatic pediatric patients whose blood lead level is < 70 mcg/dL but > 20 mcg/dL (World Health Organization recommended upper allowable level):

1000 mg/m2/day given intravenously or intramuscularly

Therapy of lead poisoning in pediatric patients with edetate calcium disodium is continued over a period of five days. Therapy is then interrupted for 2 to 4 days to allow redistribution of the lead and to prevent severe depletion of zinc and other essential metals. Two courses of treatment are usually employed; however, it depends on severity of the lead toxicity and the patient's tolerance of the drug.

Edetate calcium disodium is equally effective whether administered intravenously or intramuscularly. The intramuscular route is used for all patients with overt lead encephalopathy and this route is preferred by some for young pediatric patients.

Usual Pediatric Dose for Lead Poisoning -- Severe:

When the blood lead level is > 70 mcg/dL or clinical symptoms consistent with lead poisoning are present, it is recommended that edetate calcium disodium be used in conjunction with BAL (dimercaprol). Clinician should consult latest published protocols and/or a local poison control information center for dosing.

Other drugs may interact with edetate calcium disodium, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Specific Drugs

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• This medicine is most often given as a shot into a muscle.
• It may be given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Not hungry.
• More thirst.
• Fever or chills.
• Feeling tired or weak.
• Headache.
• Muscle or joint pain.
• Dry lips.
• Sneezing.
• Stuffy nose.
• More tears.
• Pain where the shot was given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Generic: 1 g/5 mL (5 mL)

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.

Applies to edetate calcium disodium: parenteral injection

Side effects include:

Injection site pain.

For asymptomatic pediatric patients whose blood lead level is < 70 mcg/dL but > 20 mcg/dL (World Health Organization recommended upper allowable level):

1000 mg/m2/day given intravenously or intramuscularly

Therapy of lead poisoning in pediatric patients with edetate calcium disodium is continued over a period of five days. Therapy is then interrupted for 2 to 4 days to allow redistribution of the lead and to prevent severe depletion of zinc and other essential metals. Two courses of treatment are usually employed; however, it depends on severity of the lead toxicity and the patient's tolerance of the drug.

Edetate calcium disodium is equally effective whether administered intravenously or intramuscularly. The intramuscular route is used for all patients with overt lead encephalopathy and this route is preferred by some for young pediatric patients.

Edetate calcium disodium is contraindicated in patients with active hepatitis.

The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron mobilized are not significant. Copper 1 is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased. 1

Edetate calcium disodium is poorly absorbed from the gastrointestinal tract. In blood, all the drug is found in the plasma. Edetate calcium disodium does not appear to penetrate cells; it is distributed primarily in the extracellular fluid with only about 5% of the plasma concentration found in the spinal fluid.

The half life of edetate calcium disodium is 20 to 60 minutes. It is excreted primarily by the kidney, with about 50% excreted in one hour and over 95% within 24 hours. 2 Almost none of the compound is metabolized.

The primary source of lead chelated by Calcium Disodium Versenate is from bone; subsequently, soft-tissue lead is redistributed to bone when chelation is stopped. 3,4 There is also some reduction in kidney lead levels following chelation therapy.

It has been shown in animals that following a single dose of Calcium Disodium Versenate urinary lead output increases, blood lead concentration decreases, but brain lead is significantly increased due to internal redistribution of lead. 5 (See WARNINGS .) These data are in agreement with the recent results of others in experimental animals showing that after a five day course of treatment there is no net reduction in brain lead. 6