As part of its continuing efforts to provide the American public access to treatments in the event of a terrorist attack, the Food and Drug Administration (FDA) today announced that it had determined conditions under which two drugs, pentetate calcium trisodium (Ca-DTPA) and pentetate zinc trisodium (Zn-DTPA), are safe and effective for treatment of certain kinds of radiation exposure. FDA is calling for manufacturers to use these findings to submit marketing applications for Ca-DTPA and Zn-DTPA products for use as medical countermeasures.

Through analysis of the medical reports of patients treated with Ca-DTPA and Zn-DTPA in radiation contamination emergencies over the last 40 years, as well as analysis of published literature, FDA has determined that Ca-DTPA and Zn-DTPA when produced under conditions specified in approved marketing applications, can be safe and effective for the treatment of internal contamination with plutonium, americium, or curium by increasing the rate of elimination of these radioactive substances from the body. FDA is, therefore, now encouraging the submission of new drug applications for these products.

“One of FDA’s most urgent new challenges is to protect Americans from heightened threats of terrorism,” said FDA Commissioner Mark B. McClellan, M.D., Ph.D. “We are doing all we can to help product developers provide safe and effective countermeasures for biological, chemical, and radiological attacks.”

For several decades, Ca-DTPA and Zn-DTPA have been used as investigational drugs to enhance the excretion of plutonium, americium, and curium from the body into the urine. Currently there are no approved drug products containing Ca-DTPA or Zn-DTPA.

Contamination with plutonium, americium, or curium can occur through a variety of routes including ingestion, inhalation, or wounds and can cause serious illness or death when high radiation doses are absorbed and delivered to critical organs. At lower doses such contamination has been associated with the development of cancer.

The radioactive isotopes of plutonium, americium and curium are found in the fallout from the detonation of nuclear weapons and the waste from nuclear power plants. In addition, contamination by radioactive elements such as these is of particular concern because of the potential use of such elements as components of a conventional explosive device containing radioactive material, commonly called a "dirty bomb." Although this radiological dispersal device is not a nuclear bomb, it’s detonated as a means to spread radioactive material and contaminate people and property.

The DTPAs are usually given intravenously. The main possible side effect of Ca-DTPA is the loss of important minerals in the body. Although Zn-DTPA causes this side effect to a lesser degree, it is also less effective than Ca-DTPA if given during the first 24 hours of radiation contamination. After 24 hours, Ca-DTPA and Zn-DTPA appear to be equally effective. When the sources of radiation contamination are multiple or unknown other drugs (such as potassium iodide or Prussian blue) can be used together with Ca-DTPA or Zn-DTPA.

To help potential sponsors bring these products to market, the agency has prepared draft labeling developed by FDA along with a guidance document, "Calcium-DTPA and Zinc-DTPA Drug Products--Submitting a New Drug Application" on how to submit these marketing applications.

Today’s action is part of a continuing effort by the agency to foster the development and availability of medical countermeasures to terrorist attacks. This call for applications is the second time this year that FDA has sought to bring products to treat radiation injury to the market. In February 2003, FDA announced that it had determined Prussian blue to be safe and effective when produced under conditions specified in approved marketing applications, for the treatment of exposure with radioactive thallium, non-radioactive thallium, or radioactive cesium, and encouraged the submission of NDAs for Prussian blue products.

More information about FDA’s efforts to counteract bioterrorism is available on FDA’s website at http://www.fda.gov/oc/opacom/hottopics/bioterrorism.html.

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