Consumer medicine information

Disodium Edetate Solution

Disodium edetate

BRAND INFORMATION

Brand name

Biological Therapies Disodium Edetate Solution

Active ingredient

Disodium edetate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Disodium Edetate Solution.

What is in this leaflet

This leaflet answers some common questions about Disodium Edetate Solution 3g in 100mL Concentrated Injection for Intravenous Infusion.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of giving Disodium Edetate Injection against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Disodium Edetate Injection is used for

Disodium Edetate Solution 3g in 100mL Concentrated Injection must be diluted before it is used.

Disodium Edetate Solution 3g in 100mL Concentrated Injection contains the active ingredient Disodium Edetate.

Disodium Edetate belongs to a group of substances called chelating agents. Chelating agents are used to remove high levels of mineral deposits from the body. They work by tightly binding on to the mineral so that it can be excreted from the body, usually in the urine.

This medicine may be used to remove small amounts of lead from the body if the lead is causing problems in the body.

Since Disodium Edetate will bind to a wide range of metals, it will also bind with various toxic and radioactive metals that you may have ingested or inhaled, such as radioactive calcium, strontium, radium cobalt and plutonium. Disodium Edetate will not treat radiation poisoning; it is used only to remove metals, which may be radioactive.

Too much calcium in the blood is called hypercalcaemia. Disodium Edetate Injection can also be used to remove excess calcium from the blood if the excess calcium is causing problems in the body. Disodium Edetate works by binding with the excess calcium in the blood. The calcium and disodium edetate are then removed from the blood by the kidneys and excreted in the urine.

Disodium Edetate Injection can also be used to control abnormal heart beat which is caused by an overdose of the drug called digitalis.

Your doctor may have prescribed Disodium Edetate for another reason. Ask your doctor if you have any questions about why Disodium Edetate has been prescribed for you.

Disodium Edetate is not addictive.

Disodium Edetate is only available from a medical practitioner.

Before you are given Disodium Edetate Injection

When you must not be given it:

Do not have Disodium Edetate Injection given if:

  • You have a known allergy to Disodium Edetate or other EDTA drugs
    Symptoms of an allergic reaction may include skin rash; itchiness; shortness of breath; swelling of the face, lips, mouth or throat.
  • You have inadequate kidney function
    Disodium Edetate is mostly excreted in the urine and may make kidney disease worse.
  • You have active liver disease
    Disodium Edetate Injection should not be given if you have hepatitis or cirrhosis of the liver.
  • You have a history of tuberculosis
    Disodium Edetate is mostly excreted in the urine and may make kidney disease worse.
  • You are using other chelating agents
    You should not be given Disodium Edetate Injection if you are having other chelating medicines given by mouth or by injection, unless your doctor recommends it.
  • The contents of the bottle have not been diluted before injection
    Disodium Edetate MUST be diluted before injection.
  • The solution for injection is not clear or contains particles
  • The solution has not been prepared on the same day as it is to be given
    Significant changes in acidity can occur in the diluted solution if it is not used on the same day as preparation and this can be harmful to you.
  • The packaging is torn or shows signs of tampering
  • The expiry date (Exp.) printed on the pack has passed
    If you have this medicine after the expiry date, it may not work and it may be harmful to you.

If you are not sure whether you should have Disodium Edetate Injection given, talk to your doctor.

Before you have it injected:

If you have any of the following medical illnesses or conditions, you must tell your doctor. Your doctor will discuss the risks and benefits of using Disodium Edetate Injection if you have any of these illnesses or conditions.

  • Tell your doctor if you have had an allergy to any of the ingredients in this medicine, any other medicines or any other substances, such as foods, preservatives or dyes
  • Tell your doctor if you have or have had kidney disease or problems passing urine.
  • Tell your doctor if you have high blood pressure
  • Tell your doctor if you have a history of heart failure or heart disease
  • Tell your doctor if you have a history of seizures or epilepsy
  • Tell your doctor if you have a history of Tuberculosis
  • Tell your doctor if you have low levels of calcium or potassium in the blood
  • Tell your doctor if you are pregnant or intending to become pregnant
  • Tell your doctor if you are breastfeeding or are intending to breastfeed
    Your doctor will discuss the risks and benefits of using Disodium Edetate Injection while pregnant or breastfeeding

If you have not told your doctor about any allergies you might have, tell them before you have Disodium Edetate Solution Injected.

If Taking Other Medicines:

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Disodium Edetate Injection may interfere with each other. These include:

  • Medicines used to treat heart disease such as Digoxin;
  • Other Chelation Medicines such as DMPS, DMSA, D-Penicillamine;
  • Anticoagulants;
  • Vitamin and Mineral Supplements

These medicines may be affected by Disodium Edetate Injection, or may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. It is recommended you stop taking any mineral supplements 24 hours before Disodium Edetate Injection is given. Your doctor will advise you about this.

Your doctor or pharmacist has more information about medicines to be careful with, use correctly or to avoid while you are being treated with Disodium Edetate.

How Disodium Edetate Injection is given

Disodium Edetate Injection must only be given by a doctor or nurse.

Disodium Edetate 3g in 100mL Solution is a Concentrated Injection and must be diluted with a compatible intravenous solution before use.

Other medicines will be mixed with Disodium Edetate before it is given to you.

It will then be infused intravenously (slowly injected into a vein) by your doctor. Your doctor will decide the best way to do this.

Disodium Edetate Solution for Injection must be used on the same day it is mixed or diluted.

How much is given:

Your doctor will tell you how much Disodium Edetate Injection will need to be given and for how long it is to be given. This is determined by many factors including your body weight and your medical condition.

The maximum dose in any 24-hour period is 3 grams.

Follow all directions given to you by your doctor carefully. They may differ from the information contained in this leaflet.

How long to use it:

Each person will respond differently to Disodium Edetate Injection.

Treatment times will differ depending on the reason for prescribing Disodium Edetate Injection.

Your treatment using Disodium Edetate Injection will be individually tailored to your needs by your doctor. It is usual that several treatments may be necessary. Each treatment may take 3-4 hours, however your doctor will advise you as to the length and frequency or treatment.

If you forget an appointment or need to change an appointment:

You will need to make another appointment as soon as possible.

If you are not sure what to do, contact your doctor or pharmacist as soon as possible.

If too much is given (overdose):

Your doctor should be the only person to inject Disodium Edetate Solution, so an overdose is not likely to occur.

But if you think that you or anyone else may have been given too much Disodium Edetate Injection immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) or go to accident and emergency at your nearest hospital. Do this even if there are no signs of discomfort or poisoning.

Immediately contact your doctor or nurse if you notice the following symptoms of an overdose:

  • Abdominal cramps
  • Shortness of breath or difficulty breathing
  • Irregular heartbeat
  • Confusion, mood or mental changes
  • Muscle cramps in hands, arms, feet, legs or face
  • Numbness and tingling around the mouth, fingertips or feet
  • Shaking or tremors
  • Convulsions, fits or seizures.

While you are being given Disodium Edetate Injection

Things you must do:

  • Tell all doctors, dentists and pharmacists who are treating you that you are being treated with Disodium Edetate Injection.
  • If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being treated with Disodium Edetate Injection.
  • Tell your doctor if you become pregnant while being treated with Disodium Edetate Injection.
  • Tell your doctor if you feel that giving Disodium Edetate Injection is not helping your condition.

Disodium Edetate treatment must be monitored very closely by your doctor. You may need to have regular blood tests and urine tests, and have your blood pressure checked regularly.

Be sure to keep all appointments with your doctor so that your progress can be checked.

Things you must not do:

  • Do not inject Disodium Edetate Solution yourself.
  • Do not take any other medicines, whether they require a prescription or not, without first telling your doctor or consulting a pharmacist.

Things to be careful of:

Be careful driving or operating machinery until you know how Disodium Edetate affects you. This medicine may cause dizziness, light-headedness or weakness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given or treated with Disodium Edetate Injection.

Disodium Edetate helps most people but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or nurse if you notice any of the following and they worry you:

  • Skin irritation and/or pain around the area of injection
  • Bruising around the area of injection
  • Stomach cramps
  • Diarrhoea
  • Dizziness or light-headedness
  • A general feeling of being unwell

The above list includes the more common side effects of this medicine.

Tell your doctor or nurse as soon as possible if you notice any of the following

  • Headache
  • Tingling feeling or pins and needles, numbness or prickling feelings
  • Temporary numbness of the mouth, or temporary numbness anywhere else
  • Fever
  • Burning, crawling or itching feeling
  • Sores in the mouth and on lips and dry scaly skin

The above list includes serious side effects that may require medical attention or hospitalization.

Tell your doctor immediately, or go to accident and emergency at your nearest hospital if you notice any of the following:

  • cloudy urine or changes in your urination habits
  • unexplained back pain
  • extreme numbness or tingling, difficulty moving fingers or toes
  • Muscle spasms or tremors
  • Excessive thirst
  • Pain, burning or swelling at the site of injection
  • Unusual tiredness or weakness
  • Skin rashes or sores
  • Flu like symptoms such as chills or fever
  • Severe pain or inflammation of the feet, knees, hands, or elbows

Symptoms of kidney problems:

  • Cloudy urine
  • Frequent or sudden urge to urinate
  • Large or small volumes of urine
  • Pain or difficulty urinating

Symptoms caused by low levels of calcium in the blood:

  • Difficulty breathing
  • Irregular heartbeat
  • Mood or mental changes
  • Muscle spasms in hands, arms, feet, legs or face
  • Numbness or tingling around the mouth, fingertips or feet
  • Fits or seizures

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

Ask your doctor or pharmacist if you don’t understand anything in this list.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

How to Store Disodium Edetate Solution 3g in 100mL Concentrated Injection

Store below 30°C.

Keep out of reach of children.

This product is for SINGLE USE in one patient on one occasion only. It will be used once only and then it will be discarded. It must never be stored after it is opened, nor used for more than one person.

Product Description

Ingredients:

Active Ingredient:
Disodium Edetate 3g

Other Ingredients
Water for Injections.

This medicine does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes, alcohol or any preservatives.

What it looks like:

Disodium Edetate Solution 3g in 100mL Concentrated Injection is a clear and colourless solution in a clear glass vial, sealed with a rubber stopper and an aluminium cap.

Supplier

Disodium Edetate Solution 3g in 100mL Concentrated Injection is supplied and manufactured in Australia by:

Biological Therapies
A Division of Orthomolecular Medisearch Laboratories Pty Ltd.
Suite 5, 20-30 Malcolm Road
Braeside VIC 3195

Australian Registration Numbers:

AUST R 22279

Date this document last updated: 20 February 2010

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Biological Therapies Disodium Edetate Solution

Active ingredient

Disodium edetate

Schedule

S4

 

Name of the medicine

Disodium Edetate is the Disodium salt of EDTA (ethylenediamine tetra-acetic acid) dihydrate.

Description

Biological Therapies supplies Disodium Edetate as a sterile, nonpyrogenic, concentrated solution. Further dilution and pH adjustment of the solution must occur before infusion (see Dosage and Administration).
Disodium Edetate has a molecular weight of 372.2. It is a white odourless crystalline powder soluble 1 in 11 of water; slightly soluble in alcohol.17 The BP specifies that a 5% solution in water has a pH of 4.0 to 5.5.15 Various injectable preparations of Disodium Edetate are described in the Handbook of Injectable Drugs17, Martindale15, The Merck Index18, and the USP23.
As a result of pH adjustment, the administering infusion will contain varying amounts of the disodium and trisodium salts23. Also, the inclusion of MgSO4 in the infusion solution (as described in Dosage and Administration) will produce some Magnesium Disodium Edetate which helps reduce the pain of administering EDTA.

Pharmacology

EDTA is a chelating agent, that is, it incorporates a heavy metal ion into a ring structure. The biological half-life of EDTA in humans is about one hour.28 About 1-2% remains in the body after 24 hours and 0.5% after 48 hours. The chelated EDTA passes through the bloodstream and is mostly excreted through the kidneys (95%) into the urine. The remainder of the EDTA passes through the liver and is excreted in the bile and through the intestinal tract (5%). Metal ions, forming more stable complexes with EDTA, compete with ions forming less stable complexes. The order of strength of complex of metal ions with EDTA is as follows:
Co+++ Most stable
Fe+++
Hg++
Cu++
Pb++
Ni++
Zn++
Cd++
Co++
Al+++
Fe++
Mn++
Ca++
Mg++ Least stable
with Co+++ forming the most stable complex and Mg++ forming the least stable complex.25
Since EDTA will also be removing essential elements, including, iron and zinc (and calcium), as well as undesirable lead and cadmium, it is important that the physician provide the patient with appropriate supplementary mineral intake during and/or after the process of chelation.24, 25, 26, 27 No evidence of iatrogenic osteoporosis has been observed as a result of Disodium Edetate infusion.29
Sodium Ascorbate is routinely added to Disodium Edetate because it acts synergistically as a weak chelating agent and has antioxidant activity helping to protect tissues during metal mobilisation.
It has been determined that 3 g of intravenous Disodium Edetate could theoretically remove about 324 mg of Ca++. Since the total serum calcium level is only about 400 mg, if Disodium Edetate is infused too quickly, it can cause a precipitous drop in serum calcium, with a resultant hypocalcaemic tetany. Provided due care is taken to infuse the EDTA slowly, the calcium excreted as the EDTA chelate is replaced at the same time by the calcium from the miscible pool of calcium in the extracellular fluids and soft tissues, which contain approximately 4 to 5 grams of calcium. A slow drip rate also ensures that significant quantities of the calcium complexed in the Ca-EDTA molecule will be co-exchanged with the undesirable Pb++, Hg++, Cd++, Al+++, some Fe+++, Zn++, Mn++ etc. will also be complexed with EDTA. As these ions produce more stable complexes than Ca-EDTA, their excretion further reduces the overall depletion of serum calcium.
Disodium Edetate is particularly effective in treating low level lead accumulation and low level lead poisoning. This is especially so where there is a concomitant hypercalcaemic problem. However it must be noted that Disodium Edetate is equally effective with Calcium Disodium Edetate in removing heavy metals, even in the absence of hypercalcaemia.27 For patients with elevated serum calcium or hypermobility of their body pools of calcium where there may be transiently or prolonged raised serum calcium, the EDTA of choice for removing heavy metals may be Disodium Edetate.
There are no recognised safe limits for lead intoxication.22 Lead poisoning may occur by ingestion or inhalation of lead dust or fumes. Poisoning is manifested by a metallic taste, anorexia, irritability, apathy, abdominal colic, vomiting, diarrhoea, constipation, headache, leg cramps, black stools, oliguria, stupor, convulsions, palsies and coma. Chronic lead poisoning causes variable involvement of the Central Nervous System, the blood forming organs and the gastrointestinal tract. Diagnostic laboratory tests include blood lead, hair analysis, urine coproporphyrin, urine δ-aminolevulinic acid, x-ray of abdomen and x-ray of long bones.19,20 Comparing the results of a 12-hour urine collection, pre-EDTA therapy, with the results of a 12-hour urine collection, during/post initial EDTA chelation, should confirm the early excretory surge of lead. As long as significant quantities of lead remain in the bone, any intercurrent illness which causes demineralisation can cause mobilisation of toxic quantities of lead into soft tissues and exacerbate plumbism.
Disodium Edetate may be used to temporarily reduce serum Calcium in patients with hypercalcaemia.2, 3, 15 Transient or prolonged hypercalcaemia may exceed the solubility product of calcium and result in tissue damage. Increased plasma calcium may give rise to renal lithiasis or acute pancreatitis. Calcium may also precipitate in the eyes (band keratopathy) and in soft tissues around the joints. There are many primary and secondary causes of transient and prolonged hypercalcaemia, which include the following:
i) The injection of Calcium Disodium EDTA may itself give rise to a transient hypercalcaemia.
ii) Immobilisation, which may be associated with all sorts of conditions. For example, in Paget's Disease it is sometimes warranted to supplement with calcium unless there is chronic immobilisation (greater than 3 days immobilisation in bed may precipitate a hypercalcaemia), in which case patients should be placed on a calcium restricted diet.
iii) Increased ingestion and uptake of calcium, as in dairy foods or calcium supplements such as calcium citrate.
iv) Increased ingestion and uptake of vitamin D.
v) Hypervitaminosis A.
vi) Osteoarthritis, Rheumatoid Arthritis, Hyperthyroidism, Hyperparathyroidism, Malignancies, Multiple Myeloma, prolonged use of Heparin, Immunosuppressant Drugs, Acromegaly.

Indications

1. Disodium Edetate is particularly effective in treating low level lead accumulation and low level lead poisoning.
This is especially so where there is a concomitant hypercalcaemic problem (see Indications (2)). However it must be noted that Disodium Edetate is equally effective with Calcium Disodium Edetate in removing heavy metals, even in the absence of hypercalcaemia.27 For patients with elevated serum calcium or hypermobility of their body pools of calcium where there may be transiently or prolonged raised serum calcium (see Indications (2)), the EDTA of choice for removing heavy metals may be Disodium Edetate.
There are no recognised safe limits for lead intoxication.22 Lead poisoning may occur by ingestion or inhalation of lead dust or fumes. Poisoning is manifested by a metallic taste, anorexia, irritability, apathy, abdominal colic, vomiting, diarrhoea, constipation, headache, leg cramps, black stools, oliguria, stupor, convulsions, palsies and coma. Chronic lead poisoning causes variable involvement of the Central Nervous System, the blood forming organs and the gastrointestinal tract. Diagnostic laboratory tests include blood lead, hair analysis, urine coproporphyrin, urine δ-aminolevulinic acid, x-ray of abdomen and x-ray of long bones.19, 20 Comparing the results of a 12-hour urine collection, pre-EDTA therapy, with the results of a 12-hour urine collection, during/post initial EDTA chelation, should confirm the early excretory surge of lead. As long as significant quantities of lead remain in the bone, any intercurrent illness which causes demineralisation can cause mobilisation of toxic quantities of lead into soft tissues and exacerbate plumbism.
2. Disodium Edetate may be used to temporarily reduce serum Calcium in patients with hypercalcaemia.2, 3, 15
Transient or prolonged hypercalcaemia may exceed the solubility product of calcium and result in tissue damage. Increased plasma calcium may give rise to renal lithiasis or acute pancreatitis. Calcium may also precipitate in the eyes (band keratopathy) and in soft tissues around the joints. For causes of hypercalcaemia see Pharmacology.
3. Disodium Edetate may be valuable in the management of severe digitalis arrhythmias, when a rapid response is required.11, 15, 17
4. Disodium Edetate is useful in helping to eliminate some radioactive metals, including Calcium, Strontium, Radium, Cobalt and the very toxic Plutonium.26, 3

Contraindications

Inadequate renal function.
Active liver disease.
History of tuberculosis.
Hypocalcaemia.
Do not inject disodium edetate intramuscularly.

Precautions

Note.

a) For patients who do not have a hypercalcaemic problem or who have a frank hypocalcaemia, Calcium Disodium EDTA may be used to treat low level lead poisoning.
b) Disodium Edetate chelates minerals. Magnesium should be added to the infusion to reduce pain and venus wall spasm at the site of the infusion. Constant monitoring of the patient for signs of hypocalcaemic tetany should occur. Disodium EDTA is a strong chelator of Zn. Zn supplementation should be considered after each chelation treatment.

1. Use with caution in the following circumstances.

Care should be taken with patients who have high blood pressure and/or a previous history of kidney disease. Under these circumstances, appropriate dose restrictions in initial phases of treatment may be warranted. The adult daily dose of Disodium Edetate may be restricted to as little as 1 gram per 60 kg bodyweight. EDTA should not be administered to patients with a high serum creatinine, or a decreased creatinine clearance.

2. Check the following before use.

Care should be taken with patients who are on anticoagulants, or have a history of congestive cardiac failure or history of seizures.

3. Carcinogenicity/mutagenicity.

There are no documented accounts of the potential for carcinogenic or mutagenic effects of Disodium Edetate.

4. Use in pregnancy or lactation.

Use in pregnancy.

Disodium Edetate Injection should be given to a pregnant woman only if clearly needed.

Use in lactation.

The safety of this product in nursing mothers has not been established.

5. Interactions with other drugs.

EDTA should, in general, not be given with other chelating agents such as DMPS, DMSA and D-Penicillamine. However some experts recommend the simultaneous administration of Calcium EDTA and dimercaprol(BAL) for the treatment of severe acute lead poisoning.

6. Effects on laboratory tests.

The oxalate method of determining serum calcium levels may give low readings in the presence of disodium edetate: a different method may be required for accuracy. The least interference will be noted immediately before a subsequent dose is administered.

Interactions

See Precautions.

Adverse Effects

Warning.

Disodium Edetate is capable of producing toxic and potentially fatal effects. The dosage schedule should be followed and at no time should the recommended daily dose be exceeded.
1. Gastrointestinal symptoms such as nausea, vomiting and diarrhoea are fairly common following administration of this drug.
Transient symptoms such as circumoral paresthesia, numbness and headache and a transient drop in systolic and diastolic blood pressure may occur.
Thrombophlebitis, febrile reactions, hyperuricemia, anaemia, exfoliative dermatitis and other toxic skin and mucous membrane reactions have been reported.
2. Nephrotoxicity and damage to the reticuloendothelial system with haemorrhagic tendencies have been reported with excessive dosages.

Dosage and Administration

Do not inject the solution before further dilution. See Suggested Protocol section for instructions about further dilution and administration.

1. For the removal of lead and treatment of lead poisoning.

An initial test dose of 20 mg Disodium Edetate per kg body weight may be a useful check of the patient's sensitivity to EDTA. The usual adult daily dose is 50 mg/kg with a maximum of 3 grams in 24 hours. This dose is usually given daily for 5 days, followed by 2 days without the drug. This cycle is repeated two more times. Less frequent doses over a longer period of time could be considered for patients with low level lead intoxication. Creatinine clearance should be measured at each infusion and treatment schedule varied if clinically indicated.
For children, the usual dose is 40 mg/kg/day. The dose is added to sufficient saline or 5% dextrose to yield a concentration of Disodium Edetate no greater than 30 mg/mL. All the usual mineral supplements on a pro-rata body weight basis may still be added to the infusion. This solution is then administered over 3-4 hours.17

Note.

a) For patients who do not have a hypercalcaemic problem, or who have a frank hypocalcaemia, calcium disodium edetate may be used to treat low level lead poisoning.
b) Intramuscular calcium disodium edetate may be particularly useful in patients with lead encephalopathy (where there is no hypercalcaemia), where there may be increased intracranial pressure and excess fluids must be avoided.
Rapid intravenous infusions may be lethal by suddenly increasing intracranial pressure in this group of patients with cerebral oedema. Symptoms of acute increased intracranial pressure should be treated before commencing EDTA infusion.

Suggested general protocol for disodium edetate infusion for 60 kg adult subject to review by administering physician.

Disodium Edetate is administered by slow intravenous infusion over at least 3-4 hours. It must be diluted prior to administration, usually in 500 mL of water for injection or 500 mL of half-strength saline (0.45% sodium chloride) or in 500 mL of 5% glucose for injection depending on the clinical indications. If water or half-strength saline are used, the solution must be adjusted to at least isotonic before administration. Potassium may be added if the patient is hypokalaemic.
Magnesium Sulfate is often added to reduce spasm and pain at the site of infusion. 2000 units of Heparin may be added to reduce clotting at the site of injection but may be contraindicated in patients on systemic anticoagulants. Sodium Ascorbate is often added because it acts synergistically as a chelating agent and it may be used to adjust tonicity to isotonic. Procaine Hydrochloride will help reduce the pain at the site of injection. Additionally, the pH needs adjustment to approximately 7.0 to 7.4; this can be achieved with 8.4% Sodium Bicarbonate.

NB.

Infusion should occur on the same day as preparation in order to avoid significant changes in pH. Each ingredient of the infusion must be added individually and mixed prior to adding the next ingredient to the carrier solution.

2. For hypercalcaemia.15

Transient or prolonged hypercalcaemia can have numerous causes (See Pharmacology). There are documented accounts of temporary relief from hypercalcaemia due to various bone disorders.2, 3 In these studies, trisodium edetate was employed and the doses varied from 25-235 mg/kg body weight. The appropriate dose would need to be carefully assessed according to the patient's calcium status, age, weight and clinical condition. As always, constant monitoring should occur for signs of hypocalcaemic tetany. In general, a similar infusion protocol, as for lead poisoning, should be adopted (see Suggested general protocol for disodium edetate infusion for 60 kg adult).

3. For digitalis arrhythmia.15, 17

The basis for this use is that calcium ions potentiate the action of digitalis and therefore digitalis effects are reduced in the presence of lower calcium levels. Dose regime would need to be considered carefully by the supervising physician and the patient should be constantly monitored for signs of hypocalcaemic tetany, convulsions, respiratory arrest and dysrhythmia. In the following description, trisodium edetate was employed.
An infusion of 4 g trisodium edetate in 250 mL of 5% dextrose given in 10-15 minutes will lower the serum calcium sharply and often relieves arrhythmia for a time.11 For Disodium Edetate, doses of 15 mg/kg/hour up to 60 mg/kg/day have been recommended for adults and children.17

NB.

(i) Infusion should occur on the same day as preparation in order to avoid significant changes in pH.
(ii) 8.4% sodium bicarbonate may be used to adjust the pH to approximately 7 to 7.4.

4. For helping to eliminate some radioactive metals including calcium, strontium, radium, cobalt and the toxic plutonium.

For low level poisoning, a similar dose protocol to lead poisoning is suggested.27, 3

Monitoring.15, 16

1. Constant monitoring of the patient should occur for signs of hypocalcaemic tetany, convulsions and respiratory arrest. Plasma calcium levels should be monitored.
2. Patients should be monitored for irregularities of cardiac rhythm. Blood pressure and pulse should be monitored.
3. Severe acute lead poisoning by itself may cause proteinuria and microscopic haematuria. Disodium Edetate may produce the same signs of renal damage. Routine urinalysis should be performed during each course of therapy to determine whether the proteinuria and haematuria is improving or the evidence of renal tubular injury is worsening. The presence of large renal epithelial cells or increasing number of red blood cells in the urinary sediment or greater proteinuria call for immediate stopping of disodium edetate administration. Evidence of renal impairment should also be checked by serum creatinine and/or 24-hour urinary creatinine clearance.
4. Acutely ill individuals may be dehydrated from vomiting. Since disodium edetate is excreted almost exclusively in the urine, it is very important to establish urine flow by intravenous infusion (where clinically indicated) before the first dose of the chelating agent is given. Administration of disodium edetate should be stopped whenever there is cessation of urine flow to avoid unduly high tissue levels of the drug.
5. Disodium Edetate depletes some minerals and trace elements. Following each chelation therapy, patients should receive as a minimum a high potency mineral/trace element supplement. Zinc is especially prone to removal by the edetates.

Note.

Trace elements can be toxic in excess.

Overdosage

1. Too rapid intravenous infusion of Disodium Edetate (EDTA) or too high concentration may lower the serum calcium level precipitously and cause hypocalcaemic tetany. This can be fatal. Serum calcium levels should be monitored.
Patients should be under constant observation for signs of tetany. If this occurs then the infusion should be discontinued and appropriate calcium gluconate injections administered immediately.
2. Renal damage, haemorrhagic tendency, and damage of the reticuloendothelial system have been reported from excessive dosage. Creatinine Clearance tests should be performed both before and after treatment. Daily urinalysis should be performed during the treatment period. The dosage should be reduced if there is a worsening of the urinary findings.

Presentation

AUST R 22279 - Disodium Edetate Solution 3 g in 100 mL Concentrated Injection presented in a clear glass vial containing 3 g Disodium Edetate in Water for injections.
Supply of this preparation without prescription is illegal. Keep out of reach of children.

Storage

Store below 30°C.

References

1. Proc. Soc. exp. Biol. (1953) 84:359
2. J. Lab. Clin. Med. (1956) 47:29
3. Science (1953) 117:331
4. Arch. Ophthal. (1952) 48:681
5. Arch. Ophthal. (1954) 52: 846
6. California Med. (1954) 81:221
7. Proc. Soc. exp. Biol. (1953) 84:338
8. Amer. J. Clin. Path. (1952) 22:192
9. Science (1951) 114:462
10. New Engl. J. Med. (1965) 273:35 & 93
11. Brit. Med. J. (1954) 1:613
12. Lancet (1963) 2:119
13. Lancet (1967) 1:124
14. Lancet (1966) 1:81
15. Martindale 29th ed (1989) p841
16. MIMS Annual (1988) p19-977
17. Trissel, LA., Handbook of Injectable Drugs. 6th ed (1990) p299
18. The Merck Index. 11th ed. (1989) p550
19. Krupp, Chatten, Margen. (1971) Current Diagnosis and Treatment. P826
20. Harrison's Principles of Internal Medicine, 7th ed (1974) pp669-670
21. Dreisbach, Roberston. (1987) Handbook of Poisoning 12 ed. pp85-87
22. N Engl J Med (1972) 286 (13): 702-10
23. U.S. Pharmacopoeia (1990) National Formulary pp492-493
24. Skoog, DA & DM West (1969) Volumetric methods based on complex-formation reactions. Fundamentals of analytical chemistry. Holt, Rinehart & Winston,Inc. NY pp338-360
25. Welcher, FJ (1958) The analytical uses of EDTA. D. Van Nostrand Co Inc Princeton p366
26. Catsch, A. (1964) Radioactive metals mobilization in medicine. Charles C. Thomas Publisher, Springfield. p170
27. Catsch A. & AE.Harmuth Hoene (1976) Pharmacology & Therapeutic Applications of agents used in heavy metal poisoning. Pharmac. Ther. A 1:1-118
28. Goodman, LS & Gilman (1966) The pharmacological basis of therapeutics. 3rd Ed. MacMillan Co., NY p1785
29. Lamar CP (1964) Angiology (15) pp379-394

Poison Schedule

S4.