FDA ENCOURAGES NEW DRUG APPLICATION SUBMISSIONS FOR PRUSSIAN BLUE AS A TREATMENT FOR THALLIUM OR RADIOACTIVE CESIUM CONTAMINATION
|FOR IMMEDIATE RELEASE|
January 31, 2003
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Today the Food and Drug Administration (FDA) called for manufacturers to submit marketing applications for Prussian blue, a mineral compound known as ferric hexacyanoferrate(II), that has been shown to be safe and effective in treating people exposed to radioactive elements such as cesium-137.
"Today's action is part of our continuing effort to foster the development and availability of countermeasures to terrorist attacks," said Tommy G. Thompson, Secretary of the Department of Health and Human Services, "We must and will do more to prepare and protect Americans against the threat of bioterrorism."
After a review of cases in published literature, FDA determined that 500-mg. Prussian blue capsules would be safe and effective for the treatment of patients with known or suspected internal contamination with radioactive thallium, non-radioactive thallium, or radioactive cesium. At this time, there are no FDA-approved treatments for internal contamination with thallium or radioactive cesium.
Prussian blue is the first therapy that would be available to immediately help reduce the body’s burden of exposure to radioactive particles (isotopes). By binding with the radioactive particles while they are in the gut, Prussian blue captures the isotopes and causes them to be eliminated from the body.
“FDA is working to protect U.S. citizens who may be exposed to radioactive materials released from terrorist attacks using a dirty-bomb,” said Dr. Mark B. McClellan, FDA Commissioner. “FDA’s guidance to industry and approved labeling for Prussian blue products gives manufacturers critical information necessary for producing an FDA-approved product to counter terrorism.”
Cesium-137 is a product found in the fallout from the detonation of nuclear weapons and in the waste from nuclear power plants. In appropriate doses, it is also used as a source of radiation for cancer treatments. Cesium-137 contamination can cause serious illness or death and has been associated with cancer occurring long after exposure.
In addition to concerns about accidental industrial and medical exposure, cesium-137 is of particular concern because it is a potential component of a conventional explosive device (a “dirty bomb”) containing radioactive material. Although this radiological dispersal device is not a nuclear bomb, it is detonated as a means to spread radioactive material.
In determining the safety and effectiveness of Prussian blue, FDA evaluated reports of a 1987 incident in Brazil, where 250 people were contaminated with cesium-137 that had been abandoned after use in a cancer clinic. The reports showed that Prussian blue reduced the time the body was contaminated with cesium-137. Additional data from the literature, including a study of 7 human volunteers contaminated with trace doses of cesium-137, and reports on 19 patients in other incidents show a similar reduction in the biological half-life of the cesium after Prussian blue administration New Drug Applications.
Thallium, occurring naturally in several minerals and ores, is very toxic. In the form of thallium sulfate, it has previously been used as a rat and ant poison, while other thallium compounds are still used in manufacturing semiconductors, photocells, and optical glass.
Thallium-201, a radioactive isotope of thallium, is used in small doses as a radio-imaging agent in clinical diagnostic procedures. Exposure to higher doses of radioactive or non-radioactive thallium causes severe gastrointestinal symptoms followed by neurological symptoms, which may cause death.
The main side effects of Prussian blue are constipation and nonspecific gastrointestinal distress. Other rare adverse events are discussed in the published literature and in the draft labeling the agency prepared. Prussian blue was first synthesized in 1704 and has been used as an industrial and artist’s pigment since 1724. It has been used experimentally since the 1960s as an orally ingested drug to increase fecal excretion of cesium and thallium from the body without it being absorbed through the intestines in the process.
FDA encourages the submission of New Drug Applications for Prussian blue drug products, which when produced under the conditions specified in the Federal Register notice assures that the product is safe and effective. Because the FDA has already completed the safety and efficacy review work, applicants need only to submit the chemistry information for the Prussian blue product they make. To facilitate the process, the agency has prepared draft labeling and has published a guidance document on how to submit these applications.