FDA: EDTA v Ca-EDTA mix-up deaths (fwd)

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FDA Public Health Advisory

http://www.fda.gov/cder/drug/advisory/edetate_disodium.htm

Edetate Disodium (marketed as Endrate and generic products)

This information reflects FDA's current analysis of data available

concerning this drug. FDA intends to update this when additional

information or analyses become available.

FDA is issuing this public health advisory to alert patients and

healthcare professionals about important safety information concerning

the drug Edetate Disodium. There have been cases where children and

adults have died when they were mistakenly given Edetate Disodium

instead of Edetate Calcium Disodium (Calcium Disodium Versenate) or

when Edetate Disodium was used for " chelation therapies " and other

uses that are not approved by the FDA. As a result, FDA is reviewing

the benefit/risk profile of Edetate Disodium to determine if the

benefits for its intended use continue to outweigh the serious risks.

These two drugs have very similar names and are commonly referred to

only as " EDTA. " As a result, the two products are easily mistaken for

each other when prescribing, dispensing, and administering them.

Edetate Disodium and Edetate Calcium Disodium work by binding with

heavy metals or minerals in the body allowing them to be passed out of

the body through the urine.

The FDA originally approved the two drugs for very specific and very

different purposes as described below.

* Edetate Disodium was approved many years ago as an emergency

treatment for certain patients with a condition called hypercalcemia

(very high levels of calcium in the blood) or certain patients with

heart rhythm problems as a result of very high amounts of digitalis in

the blood. However, there are newer drugs that have been approved

since that time that treat these conditions.

* Edetate Calcium Disodium was also approved many years ago and is

still used to reduce dangerously high blood lead levels (severe lead

poisoning). This drug is medically necessary because there are very

few other drugs available to treat severe lead poisoning.

Over time, a number of uses that are not FDA approved for these

products have evolved in clinical settings. Among these uses are the

removal of other heavy metals from the blood and the treatment of

heart disease (coronary artery disease), commonly referred to

" chelation therapies. "

On March 3, 2006, the Centers for Disease Control and Prevention

published an article in the Morbidity and Mortality Weekly Report

documenting the deaths of people given Edetate Disodium instead of

Edetate Calcium Disodium

(http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5508a3.htm). FDA was

informed early in 2007 of an additional child's death as a result of a

mix-up between the two drugs. Because of the potential for these

medication errors to be fatal, the CDC recommended that hospitals

evaluate their need to keep Edetate Disodium stocked in their

pharmacies. FDA supports this recommendation as a means of reducing

the risk of confusing the two drugs.

FDA is issuing this advisory to highlight the following important

safety considerations until the ongoing evaluation of the risks and

benefits of Edetate Disodium is complete.

* Because of the potential for these medication errors to be

fatal, the FDA and CDC recommend that hospitals evaluate their need to

keep Edetate Disodium stocked in their pharmacies.

* If your facility determines that there is no need to have a

supply of Edetate Disodium, consider removing the product from stock

to reduce the risk of confusion with Edetate Calcium Disodium.

* The safety or effectiveness of Edetate Disodium or Edetate

Calcium Disodium for use in removing heavy metals and toxins from the

body, use in treating coronary artery disease, or other uses not

described in the labeling for the product have not been established.

* Children and adults who are to be treated for lead poisoning

should only be given the Edetate Calcium Disodium (Calcium Disodium

Versenate) form of " EDTA. "

* Use the full product name. Do not use the abbreviation " EDTA "

when prescribing or dispensing an order for either of the drugs.

* Consider including the indication for use of the product on the

prescribing order.

* Hospitals, pharmacies and healthcare providers should always

check the prescribing order and the label of the drug to confirm that

the correct drug has been selected for use before dispensing and

administering the drug to a patient.

FDA will determine further regulatory actions once we complete our

evaluation of the safety and efficacy of Edetate Disodium.

The FDA asks healthcare professionals and patients to report serious

side effects that may be associated with the use of Disodium Edetate

and Edetate Calcium Disodium to the FDA through the MedWatch program

by phone (1-800-FDA-1088) or by the Internet at

http://www.fda.gov/medwatch. Adverse reactions or quality problems

experienced with the use of this Product may be reported to the FDA's

MedWatch Adverse Event Reporting program either online, by regular

mail or by fax.

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http://www.fda.gov/cder/drug/infopage/edetate_disodium/QA.htm

Questions and Answers on

Edetate Disodium (marketed as Endrate and generic products)

1. What is EDTA?

The term " EDTA " is often used to refer to two different drugs that

bind to ( " chelate " ) certain molecules within the body. This binding

speeds the elimination of these molecules from the body. For example,

when one type of EDTA drug is injected into the blood stream, it binds

to calcium and speeds excretion of calcium through the kidneys. This

type of EDTA drug has been used to treat high blood levels of calcium.

The other type of EDTA drug strongly binds to lead and has been used

to treat patients with lead poisoning.

2. What are the names of the two EDTA drugs?

There are two drugs approved by the FDA that have similar names

are easily confused. To add to the confusion, both drugs are commonly

referred to only as the abbreviation, " EDTA. "

One drug is named " Calcium Disodium Versenate " and is also known

by the chemical name of edetate calcium disodium. This drug is

approved by the FDA to lower blood lead levels among patients with

lead poisoning.

The other drug is marketed as " Endrate " and is also known by the

chemical name of edetate disodium. This drug is approved by the FDA

for use in selected patients with high blood calcium levels

(hypercalcemia) as well as for use among patients with heart rhythm

problems due to intoxication with the drug, digitalis.

3. What is the problem with the EDTA drugs?

The two EDTA drugs have established names that are easily confused

and both are referred to in clinical practice as " EDTA. " This

confusion has resulted in medication errors in which some patients

have received the wrong drug, which has been fatal in some cases or

caused serious adverse reactions in others. The error is especially

dangerous when edetate disodium is erroneously given to a patient who

is supposed to receive edetate calcium disodium.

The two EDTA drugs have different approved uses and significantly

different effects. For example, edetate disodium is more likely to

cause severe decreases in blood calcium levels. A severe decrease in

blood calcium levels due to the erroneous administration of edetate

disodium has resulted in death, predominantly among pediatric

patients, who were to be treated for lead poisoning with edetate

calcium disodium. As noted below, FDA has special concerns regarding

the use of edetate disodium and is reconsidering the overall risks and

benefits of the drug.

4. How many people have died as a result of receiving edetate disodium?

FDA has received reports of 11 deaths associated with the use of

edetate disodium. These deaths were reported over the time period

from 1971 through 2007. Most recently, two reports were received in

2003, two reports in 2005 and one report was received in 2007. Nine

of the deaths were reported following the administration of edetate

disodium (by its specific name). A specific EDTA drug was not

identified in two cases. Instead, these two death reports simply

referred to use of " EDTA. "

5. How many deaths have been reported to FDA as due to errors in

which edetate disodium was confused with another drug?

Seven of the 11 deaths resulted from confusion of edetate disodium

with another drug. In five cases, edetate disodium was administered

instead of edetate calcium disodium. In two cases, edetate disodium

was administered instead of the drug, Etomidate. Etomidate is not a

form of EDTA.

6. What action is FDA considering to address concerns related to

these medication errors?

Since the time of FDA approval of edetate disodium for use in the

treatment of hypercalcemia or digitalis toxicity, multiple new drugs

have been developed and marketed for treatment of these same

conditions. Based on the availability of other drugs that can be used

for the indications for which edetate disodium was approved, and the

safety issues related to edetate disodium, FDA is reconsidering the

overall risks and benefits of edetate disodium to determine the most

appropriate action. FDA is also issuing a Public Health Advisory

regarding edetate disodium.

7. What action is FDA considering regarding edetate calcium disodium?

FDA is issuing a Public Health Advisory regarding the medication

errors involving edetate disodium and edetate calcium disodium. FDA

is not considering additional action regarding edetate calcium

disodium at this time. Edetate calcium disodium is approved for use

in the treatment of lead poisoning. Few drugs are available for

treatment of this serious condition. Additionally, most of the deaths

following administration of an EDTA drug have involved medication

errors in which edetate disodium was given instead of edetate calcium

disodium. FDA has not received reports of any deaths resulting from

the administration of edetate calcium disodium in error.

8. Are the EDTA drugs used for purposes other than those described in

the product labels for the drugs?

Yes, both EDTA drugs have been used in various forms of

" chelation " therapies that are purported to cleanse the body of

various chemicals (such as mercury-containing chemicals) or to improve

the cardiovascular system. For example, " chelation " has been proposed

as a treatment for autism or hardening of the arteries. The FDA has

not approved the EDTA drugs for these purposes. FDA has not received

clinical data sufficient to support either the safety or efficacy of

EDTA drugs when they are used for these " chelation " purposes.

9. Is the FDA recommending that hospitals not stock edetate disodium?

If hospitals or clinics currently stock edetate disodium and

edetate calcium disodium, based on the medication errors involving the

two drugs, FDA recommends that the facilities reconsider whether it is

wise to stock both of these drugs, especially edetate disodium.

Having both EDTA drugs in stock may lead to confusion and medication

errors.

FDA encourages healthcare personnel to always vigilantly double

check the name of any EDTA drug to be sure only the correct drug is

administered to a patient.

10. Does FDA have a timeline for the completion of its review of the

safety and efficacy of edetate disodium ?

FDA does not have a specific timeline but hopes to complete its

review of the safety and efficacy of edetate disodium within several

weeks.

11. I received edetate disodium in the past. Am I at risk for death

or serious complications?

Deaths and serious reactions following edetate disodium

administration have all been reported within minutes to hours

following administration of the drug. The major risks are thought to

apply only to the short period of time after administration of the

drug.

12. Whom should I contact if I have questions about EDTA?

You should talk with your healthcare provider (for example, your

doctor, nurse, or pharmacist) about EDTA, your clinical condition and

all your medications.

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Podcast: http://www.fda.gov/cder/drug/podcast/edetate_disodium_full.htm