FDA APPROVES PYRIDOSTIGMINE BROMIDE

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Hawk
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FDA APPROVES PYRIDOSTIGMINE BROMIDE

Post by Hawk » Mon Nov 24, 2003 1:26 pm

:cry:

FOR IMMEDIATE RELEASE
PO3-08
February 5, 2003 Media Inquiries: 301-827-6242
Consumer Inquiries: 888-INFO-FDA

--------------------------------------------------------------------------------

FDA APPROVES PYRIDOSTIGMINE BROMIDE AS PRETREATMENT AGAINST NERVE GAS
The Food and Drug Administration (FDA) today announced approval of pyridostigmine bromide to increase survival after exposure to Soman "nerve gas" poisoning. The product is approved for combat use by United States military personnel.

Pyridostigmine bromide is the first drug approved under a recently issued FDA rule (frequently referred to as the "animal efficacy rule") that allows use of animal data for evidence of the drug's effectiveness for certain conditions when the drug cannot be ethically or feasibly tested in humans.

The "animal efficacy rule," which became effective on June 30, 2002, is an important component of FDA's efforts to make medical countermeasures available to treat or prevent the effects of biological and chemical agents.

FDA Commissioner Mark B. McClellan, M.D., Ph.D., said, "Today's action will help protect American troops and others from nerve agent attacks."

The "animal efficacy rule" enabled FDA to approve pyridostigmine bromide to increase survival from Soman poisoning despite the impossibility of ethically conducting human studies on the effectiveness of the drug.

The nerve agent Soman causes loss of muscle control and death from respiratory failure. Evidence of the effectiveness of pyridostigmine bromide as a pretreatment for exposure to Soman was obtained primarily from studies in monkeys and guinea pigs. This evidence shows that administration of the drug before exposure to Soman, together with atropine and pralidoxime given after exposure, increases survival. FDA believes that, based on the animal evidence of effectiveness, pyridostigmine bromide is likely to benefit humans exposed to Soman.

The agency's safety assessment is based on long-term use of pyridostigmine bromide, first approved by FDA in 1955, to treat a neuromuscular disease called myasthenia gravis. The Department of the Army has submitted data from multiple controlled trials and uncontrolled clinical experience demonstrating pyridostigmine bromide is well-tolerated at the doses intended for military use. The dose used for myasthenia gravis is higher than the dose used for pretreatment to protect against Soman.

To use this potentially lifesaving drug correctly, military personnel must carefully follow instructions and use the drug only under specific circumstances. For example, if U.S. troops faced the threat of exposure to Soman, they would be given instructions to take pyridostigmine bromide every 8 hours prior to the anticipated exposure. Soldiers will be warned that the drug is not effective and should not be taken at the time of, or after exposure to Soman.

The troops are to use the drug in conjunction with other protective measures, including chemical protective masks and battle dress garments. Furthermore, effectiveness depends on the rapid use of the antidotes atropine and pralidoxime and discontinuation of pyridostigmine bromide at the first indication of nerve gas exposure. The Department of Defense plans to provide all military personnel with extensive training, prior to deployment, on the proper use of pyridostigmine bromide, as well as other methods used in the prevention and treatment of nerve agent poisoning.

A leaflet that explains the drug's use, benefits, and side effects will be provided to military personnel when the drug is distributed. The leaflet advises that pyridostigmine bromide should not be used by persons who have a history of bowel or bladder obstruction, or sensitivity to certain medicines used during surgery (like physostigmine). Side effects that may occur include stomach cramps, diarrhea, nausea, frequent urination, headaches, dizziness, shortness of breath, worsening of peptic ulcer, blurred vision, and watery eyes.

The approved dose of pyridostigmine bromide for Soman pretreatment is one 30-mg. tablet every 8 hours. The leaflet states that pyridostigmine should be started at least several hours before exposure to Soman and emphasizes that it must be discontinued upon exposure to nerve gas, at which point the antidotes atropine and pralidoxime are given.

During the Gulf War, FDA had allowed distribution of pyridostigmine bromide under its Investigational New Drug provisions because pretreatment with this drug had the potential to help save lives if nerve agents were used.

Today's action provides FDA approval for the product.

found at this link:
http://www.fda.gov/cder/drug/infopage/P ... efault.htm


"The "animal efficacy rule" enabled FDA to approve pyridostigmine bromide to increase survival from Soman poisoning despite the impossibility of ethically conducting human studies on the effectiveness of the drug."
I guess the above means it is unethical, to test this drug on humans, would that implie that we were test subjects, and as such had forfeited our human rights, simply because we were in the military, we were not intitled to ethical treatment.


pb drug label (good information list all the side effects)
http://www.fda.gov/cder/foi/label/2003/020414lbl.pdf

Hawk :cry:
I am only one but I am one. I can not do everything but I can Do something And because I cannot do everything I will not refuse to do the something that I can do What I can do I should do And what I should do by the grace of God I will do. Edward E. Hale
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Post by Hawk » Mon Nov 24, 2003 1:32 pm

this is a slightly older news article, seems with the recent approval of PB pills that the side effects of being exposed to DEET while taking PB pills must have been addressed. After all the FDA would never allow unethical
testing of a drug on humans, I know its all in my head its just stress. :evil: :evil: The PB pills are safe just ask any Iraqi freedom vet they are'nt experiancing any mysterious health problems.

Hawk :cry:


National News
Researcher says work's tie to war illness got him fired
By DAVID OLINGER
(c) St. Petersburg Times, published January 11, 1997
GAINESVILLE - Jim Moss was looking for a better way to kill cockroaches. He found something nobody expected: a possible clue to the mysterious ailments afflicting veterans of the Persian Gulf war.

It was a discovery that would lead some to treat him as an American hero - and others to terminate his work as a federal research scientist.

What Moss found in the bodies of dying insects was a toxic relationship between two chemicals used by an estimated 250,000 American soldiers in the gulf war.

One was a potent, experimental pill - pyridostigmine bromide, or PB - that was supposed to protect soldiers against nerve gas attacks. The other was DEET, a common repellent that soldiers slathered on themselves to ward off desert insects.

At the Medical and Veterinary Entomology Research Laboratory in Gainesville, Moss showed that PB and DEET - at least for cockroaches - are synergistic. Apply them together and the effects multiply, turning a harmless dose of each into a potentially lethal combination.

He did so in defiance of his employer, the U.S. Department of Agriculture, which invented DEET in the 1950s and tested it at the lab where he worked.

In 1993, when Moss first suspected DEET might be a factor in gulf war ailments, a top USDA official called Gainesville to stop him from spreading his suspicions outside the lab, records show. The lab director told Moss to cease his "unauthorized" DEET research and warned that his career was at stake.

Clearly, the implications of Moss' research were disturbing: He thought the U.S. government might have unwittingly harmed its own troops.

By pursuing those suspicions, he demonstrated that DEET can intensify the effects of a nerve gas pill many gulf war soldiers swallowed daily without knowing its contents. He won an invitation from Sen. Jay Rockefeller to testify at a congressional hearing. He won praise from gulf war veterans and from a researcher who substantiated his findings.

But he lost his job.

In June 1994, the month after Moss appeared before Congress, his temporary appointment as a research scientist in Gainesville ended. The Agriculture Department canceled his job and his research.

Sen. Rockefeller calls that decision a shame.

Moss is a researcher "who had a tremendous amount to contribute" and a patriot who has been "junked" by his government, Rockefeller said Friday.

"He discovered through his own scientific curiosity that an insect repellent, DEET, used by perhaps 70-million Americans may in fact be implicated in a serious public problem," Rockefeller said.

Today, Moss is an unemployed scientist - and still seeking federal support to pursue his gulf war research. He has three children, a wife who works as a librarian, a house on a woodsy lane in Gainesville and a bunch of rejection letters.

"We're broke," he said.

He started with roaches

Six years after the war, gulf war illnesses remain a mystery.

Tens of thousands of soldiers have reported symptoms ranging from chronic fatigue to joint and muscle aches, memory loss and rashes. Many researchers now believe these ailments are war- related, but they differ about the causes.

This week, a presidential advisory committee suggested stress played a major part in soldiers' physical and mental symptoms. At the same time, medical school studies from the University of Iowa and University of Texas pointed to multiple chemical exposures as a more likely explanation.

Soldiers were exposed to smoke from giant oil fires Iraq ignited during the war. They were exposed to pesticides and paint fumes. They may have been exposed to chemical weapons during the war, or afterward, when the U.S. Army blew up a weapons depot that held nerve gas rockets.

Dr. Robert Haley, the author of the Texas study, attributed gulf war illnesses to "subtle brain, spinal cord and nerve damage - but not stress."

Among the chemicals his study cited as possible culprits were two that Jim Moss tested in a Florida lab three years ago: DEET and PB.

In cockroaches and in humans, there are enzymes that regulate transmissions between nerve cells. Nerve gases interfere with these enzymes, causing a massive overloading of the transmission system. So do many pesticides. And so, to a milder degree, does the PB pill given as a shield against nerve gas.

Moss thinks some agent probably intensified some soldiers' reactions to PB. He knows of two that can affect lab animals this way: stress and DEET.

Though he discovered the latter, today "I'd be much more concerned about stress and PB than DEET and PB," he said.

Moss joined this debate largely by chance. He came to Gainesville in 1990 to conduct research on insect pests, an appointment renewed in 1992.

In 1993 he was working with boric acid, a cheap and safe but rather slow treatment for cockroaches, and looking for synergists - chemicals to heighten its effect.

That November he started testing DEET with pesticides, applying droplets of each onto cockroaches immobilized in petri dishes. One was a defoliant known to raise the toxicity of some insecticides. When Moss added the same defoliant to DEET, a repellent, he got what his lab technician described as "rapid kill."

Moss got excited. He started calling other scientists to discuss his results. One was Donald Hildebrandt, at S.C. Johnson Wax. At the time, Moss said he didn't know Johnson makes Off, a leading repellent made with DEET.

Moss told Hildebrandt that DEET might have a promising new use. He also mentioned a hunch that DEET might have something to do with the illnesses being labeled gulf war syndrome.

According to statements later filed by laboratory officials, this is what happened next:

Hildebrandt called Carl Schreck, a scientist at the Gainesville lab known for his DEET research. Hildebrandt wanted to know who Jim Moss was and what he was doing with DEET. Schreck reported this to Richard Brenner, the lab's acting research leader.

Brenner, who described the Johnson company scientist as "very upset," decided to call Ralph Bram, their national program leader.

Bram called Gary Mount, the lab director. As Mount, who is now retired, recalled, "Dr. Bram was upset that Dr. Moss was doing toxicity research with DEET and had apparently discussed his preliminary work with several industry and government representatives."

With Brenner present, Mount called Moss in.

The lab director told Moss that DEET was marketed worldwide as an insect repellent and "that studies on its potential toxicity would obviously be of a sensitive nature." He told him not to discuss preliminary data with anyone outside the lab. He also told him not to gather any more data on DEET and to concentrate on an assigned project.

In Brenner's account, the lab director also asked Moss if he "was aware of the damage that unsubstantiated charges could have" on S.C. Johnson and the Department of Defense.

Further, "Dr. Mount indicated that Jim's reputation was at stake as a scientist and that his behavior certainly was not going to enhance his prospects for future employment," Brenner said.

Moss said he asked Mount to put those orders in writing. When none came, he continued his research.

Initially, Moss suspected DEET might be related to gulf war illnesses because it affects the toxicity of some pesticides. One was permethrin, which gulf war soldiers sprayed on their uniforms.

In December 1993, after being told to end his DEET research, he learned soldiers also had taken a nerve gas pill. It belonged to the same class of compounds as a common group of insecticides.

For six months Moss and his lab technician, Gregory Knue, tested the combined toxicity of DEET, PB and various insecticides on cockroaches.

This was done in an obviously tense environment. Brenner reported that Moss "was always seen carrying his laboratory notebook" as if he were guarding it. And when Moss' supervisor noticed he was "frequently observed meeting and talking to" a fellow researcher, Jack Seawright, he notified director Mount.

Mount had a chat with Seawright.

"I advised Dr. Seawright that under the current circumstances, he should be cautious about interacting with Dr. Moss and that he should not offer him guidance," he said. "I further said that he risked becoming involved in Dr. Moss' problems if he continued interacting with him."

Congressional hearing

In the spring of 1994, Moss found an ally in the U.S. Senate.

Jay Rockefeller, who chaired its Veterans' Affairs committee, was planning a hearing on military research and the Persian Gulf war. Moss called a committee staffer to talk about his research.

Convinced that Moss might have something important to say, Rockefeller called him as a witness.

On May 6, Rockefeller asked Moss for his preliminary research findings on PB and pesticides.

Moss replied that PB, permethrin - the insecticide sprayed on soldiers' clothing - and eight other pesticide compounds "increased the toxicity of the repellent DEET to some degree."

Rockefeller thanked Moss, noting "for the record, that the Department of Agriculture was not very happy about your coming here today to testify."

That was it. But today, Moss says that brief appearance gave his preliminary findings a future. "This stuff was buried until I went to the Senate hearings,"
he said. "It was buried forever."

Duke continues research

On June 30, 1994, Moss' appointment in Gainesville expired. The laboratory did not renew his appointment, and USDA did not pursue his controversial research project.

A research team led by the Duke University Medical Center's pharmacology department did.

In a 1996 study, they reported that one factor in neurological illnesses among gulf war veterans "may be the simultaneous exposure to multiple agents used to protect the health of service personnel, in particular" PB, DEET and permethrin.

That study used chickens as test animals. Mohamed B. Abou- Donia, its lead researcher, said when all three chemicals were combined, "the effect is very, very strong" - causing death at dosage levels where a single chemical was harmless.

And of Moss' research, he said, "I think he is a very fine scientist."

Matt Puglisi, the American Legion's director for gulf war veterans, credits Moss with opening a door other researchers entered.

"The ultimate flattery for Dr. Moss," he said, "is that his research seems to be getting replicated across the country."

'Outside our mission area'

After Moss lost his job in 1994, he filed a misconduct complaint against his employers. A department investigation concluded it was unfounded.

In 1996, in response to a query from Sen. Rockefeller, Agriculture Secretary Dan Glickman denied that his agency had stifled Moss' findings.

"In fact we encouraged Dr. Moss to pursue this research" with the Environmental Protection Agency and the Department of Defense, "where such biomedical work could appropriately be done," he wrote.

USDA says that it did nothing to damage Moss' career, that his DEET research was unauthorized, and that he strayed into a field outside of the department's domain and expertise.

"Let me be clear on one thing," department spokesman Robert Norton said. "Mr. Moss knew before he ever started doing any of his kind of extracurricular investigation that his appointment was supposed to terminate."

The Gainesville entomology lab "is not geared toward doing human toxicology research," Norton said. "That's what he was getting into. What he was doing was outside of our whole mission area."

Moss says USDA officials never encouraged him to take his research elsewhere. "That's bull. That never happened," he said.

To answer the charge that his work was unauthorized, he points to his job description, which listed developing synergists for pesticides as a task.

Since July 1994, Moss has applied for patents on some of his cockroach work and managed to get his DEET toxicity research published. He has worked as a substitute teacher in Gainesville schools. He has done part-time computer research work at home.

He has applied for support from the local Department of Veterans Affairs and for USDA and Defense Department jobs in other states, without success. He has a pending application with the Defense Department to study gulf war illnesses with another researcher.

To date, he says, nobody from the Defense Department has ever called to ask about his findings.
I am only one but I am one. I can not do everything but I can Do something And because I cannot do everything I will not refuse to do the something that I can do What I can do I should do And what I should do by the grace of God I will do. Edward E. Hale
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