The drug pyridostigmine bromide
Just what is it and what does it do?

Pyridostigmine Bromide (PB) is a pretreatment drug that was used in the Gulf War to protect against the chemical warfare (CW) nerve agent soman. By itself PB is not protective against CW nerve agent. Used as a pretreatment, however, PB can enhance the antidote effects of the standard atropine and 2-PAM treatments used by the U.S. military for nerve agent exposure.

All U.S. troops received packets containing PB pills during the Gulf War. The pills were intended to be self-administered upon a unit commander’s order. The Department of Defense (DoD) estimates that approximately 250,000 personnel took at least some PB during the Gulf War. Accurate assessments of PB exposure of U.S. troops is difficult because no specific records were kept of self-administered medications.

During the ground war, the threat from Iraqi chemical nerve agents was considered to be high. It was determined that the use of PB as a "pretreatment" could save the lives of service members exposed to nerve agents. The use of PB for this purpose in the Gulf War was specifically approved by the Food and Drug Administration (FDA). It was approved as an "investigational new drug" (IND), which means the drug had previously received full approval for another use, but the approval for this military purpose had not been sought before. The FDA approval was based on extensive scientific information that supported the safety of the drug.

Since 1955, the FDA has approved PB for use by persons suffering from myasthenia gravis. No long-term health problems thought to be associated with PB have been reported from persons with myasthenia gravis who regularly took PB over many years or decades. We have filed a New Drug Application in May 1996, but PB still has the status of an "investigational new drug" for nerve gas pretreatment use.

According to the FDA, its conclusion that PB was safe for use by U.S. service members during the Gulf War was based largely on the extensive cumulative experience with this drug in patients with myasthenia gravis. Typically these patients are treated with PB doses of up to 1,500 mg per day for many years, compared to the prescribed dose of 90 mg per day for a maximum of seven days during the Gulf War. The occasional reported side effects of PB include increased salivation, increased tearing, urinary urgency and frequency, nausea, vomiting, muscle weakness, abdominal cramps and diarrhea. These effects disappear when individuals stop taking PB.


A study that began in November 1994 looked at differences in the tolerances to PB between women and men. Ninety subjects, equally divided by gender and in three weight classes, took 30 mg of PB every 8 hours for 21 days (plus one dose). PB was found to be safe and well-tolerated. All side effects were mild and resolved with no treatment. Overall, the occurrence of adverse effects did not differ between the subjects who took PB or a placebo, nor were differences observed among gender or weight groups. Results from a 1-year follow-up indicated no long-term effects.

The department continues to seek FDA approval to use PB for the protection of U.S. troops against CW agents. To support this approval process, we have sponsored various research efforts since 1984 to gather information on the effects of PB pretreatment on healthy individuals. To date, the department has found no serious or long-term reactions from this research.

Additional concern has been raised about the possibility of increased health problems from PB when it is combined with other risk factors. Some researchers have hypothesized that PB in combination with stress may create central nervous system effects. The insect repellent DEET and the insecticide permethrin are most often mentioned as cofactors with PB for Gulf War illnesses.

Some researchers suggest the immediate toxicity of the organophosphate (OP) pesticides available to Gulf War veterans could have been increased from coexposure to PB, leading to the symptoms of immediate and severe poisoning. However, on-site medical personnel in the Gulf did not observe any immediate and severe effects of OP poisoning among U.S. service members.

In setting priorities for new research projects on Gulf War veterans' health issues, the Persian Gulf Veterans Coordinating Board has given priority to toxicology studies on subtoxic exposures to PB and pesticides, either alone or in combination. Several federally funded studies are now underway to assess the effects due to combined exposure to PB and other chemical risk factors.

Evidence suggests that most soldiers knew they were taking an oral drug called PB to counteract the effects of possible attack with nerve agents. It is likely, however, that most individuals were not informed that PB was an Investigational New Drug (IND) . It is also likely they did not receive enough thorough information about the possible side effects of PB. There was no effort to withhold information from the troops. Information had been prepared to distribute to them. However, it did not arrive before the fighting began.