FDA label C5F839EC-20C9-F291-CC33-658755CF3B26

CAUTION: USE AS A PRETREATMENT ONLY - USE ATROPINE AND 2-PAM AFTER SOMAN EXPOSURE - USE PROTECTIVE GARMENTS Pyridostigmine bromide is for use as a pretreatment for exposure to the chemical nerve agent Soman. Pyridostigmine alone will not protect against exposure to soman. The efficacy of pyridostigmine is dependent upon the rapid use of atropine and pralidoxime (2-PAM) after Soman exposure. [See Dosage and Administration (2) ] Primary protection against exposure to chemical nerve agents is the wearing of protective garments including masks, hoods and overgarments designed specifically for this use. Individuals must not rely solely upon pretreatment with pyridostigmine and on the antidotes atropine and pralidoxime (2-PAM) to provide complete protection from poisoning by the chemical nerve agent Soman. Pyridostigmine must not be taken after exposure to Soman. If pyridostigmine is taken immediately before exposure (e.g., when the gas attack alarm is given) or at the same time as poisoning by Soman, it is not expected to be effective, and may exacerbate the effects of a sub-lethal exposure to Soman. [See Clinical Pharmacology (12.2) ] FOR MILITARY MEDICAL USE ONLY CAUTION: USE AS A PRETREATMENT ONLY - USE ATROPINE AND 2-PAM AFTER SOMAN EXPOSURE - USE PROTECTIVE GARMENT(S) See full prescribing information for complete boxed warning . Pyridostigmine bromide is for use as a pretreatment for exposure to the chemical nerve agent Soman. Pyridostigmine alone will not protect against exposure to Soman. The efficacy of pyridostigmine is dependent upon the rapid use of atropine and pralidoxime (2-PAM) after Soman exposure. Primary protection against exposure to chemical nerve agents is the wearing of protective garments. Pyridostigmine must not be taken after exposure to Soman. If taken immediately before Soman exposure (e.g., when the gas attack alarm is given) or at the same time as poisoning by Soman, it is not expected to be effective, and may exacerbate the effects of a sub-lethal exposure to Soman.

5 WARNINGS AND PRECAUTIONS At the first sign of Soman poisoning pyridostigmine must be stopped, atropine and 2-PAM must be administered immediately. ( 5.1 ) Use with caution in persons with increased risk of anticholinergic reactions, such as persons with bronchial asthma, chronic obstructive pulmonary disease, bradycardia, cardiac arrhythmias, beta blocker treatment (increased risk of anticholinergic reactions). ( 5.2 ) Use with caution in persons with bromide sensitivity. ( 5.3 ) In case of serious adverse reactions, advise personnel to temporarily discontinue pyridostigmine and seek immediate medical attention. ( 5.4 ) 5.1 Stopping Pyridostigmine and Using Atropine and 2-PAM in the Event of Soman Exposure See Dosage and Administration (2) and Boxed Caution statement (at beginning of Full Prescribing Information). Pyridostigmine pretreatment offers no benefit against the nerve agent Soman unless the nerve agent antidotes atropine and pralidoxime (2-PAM) are administered once symptoms of poisoning appear. Pyridostigmine should be discontinued at the first sign of nerve agent poisoning since it may exacerbate the effects of a sub-lethal exposure to Soman. 5.2 Individuals at Increased Risk of Anticholinergic Adverse Reactions Pyridostigmine should be used with caution in persons with bronchial asthma, chronic obstructive pulmonary disease, bradycardia, cardiac arrhythmias, and, for example, in people being treated for hypertension or glaucoma with beta adrenergic receptor blockers. 5.3 Use in Bromide-Sensitive Individuals Caution should be taken when administering pyridostigmine bromide to individuals with known bromide sensitivity. The risks and benefits of administration must be weighed against the potential for rash or other adverse reactions in these individuals. [See Adverse Reactions (6) ] 5.4 Action in Case of Serious Adverse Reactions If personnel experience serious adverse reactions such as difficult breathing, severe dizziness, or loss of consciousness as a result of ingestion of pyridostigmine bromide, they should be advised to temporarily discontinue use of product and seek immediate medical attention. Serious adverse events should be reported to their commander and responsible medical officer.

6 ADVERSE REACTIONS The most common adverse reactions (≥ 3% ) are diarrhea, abdominal pain, dysmenorrhea, and twitch. The adverse reactions to pyridostigmine bromide are typically of two varieties, muscarinic and nicotinic. Muscarinic adverse reactions include abdominal cramps, bloating, flatulence, diarrhea, emesis, increased peristalsis, nausea, hypersalivation, urinary incontinence, increased bronchial secretion, diaphoresis, miosis, and lacrimation. Nicotinic adverse reactions are comprised chiefly of muscle cramps, fasciculations, and weakness. Pyridostigmine is a quaternary ammonium compound and does not readily cross the blood-brain barrier. Compared to the peripheral effects of pyridostigmine bromide, central nervous system manifestations are less frequent and less serious, primarily consisting of headache and vertigo, with minor and clinically insignificant changes in heart rate, blood pressure, and respiratory function. Extremely high doses may produce CNS symptoms of agitation, restlessness, confusion, visual hallucinations, and paranoid delusions. Electrolyte abnormalities, possibly resulting from high serum bromide concentrations, also have been reported. Death may result from cardiac arrest or respiratory paralysis and pulmonary edema. As with any compound containing bromide, a skin rash may be observed in an occasional patient, which usually subsides promptly upon discontinuance of the medication. Most common adverse reactions ( ≥ 3% ) are diarrhea, abdominal pain, dysmenorrhea, and twitch. ( 6 ) 6.1 Clinical Studies Experience In a controlled study of 90 healthy volunteers comparing pyridostigmine 30 mg every 8 hours to placebo for 21 days, the following incidence of adverse reactions was reported. Table 1 Incidence of Adverse Reactions ≥ 2% Reaction: % Pyridostigmine N = 60 % Placebo N = 30 Diarrhea 7 0 Abdominal Pain 7 0 Dysmenorrhea 5 0 Twitch 3 0 Myalgia 2 0 Dry Skin 2 0 Urinary Frequency 2 0 Epistaxis 2 0 Amblyopia 2 0 Hypesthesia 2 0 Neck pain 2 0 Other less common adverse reactions seen during controlled and uncontrolled clinical trials for pyridostigmine include the following: Pulmonary: Exacerbation of acute bronchitis and asthma Cardiovascular: Elevated blood pressure, decreased heart rate (4-6 beats per minute), chest tightness Eyes: Change in vision, eye pain Neurologic: Headache, hypertonia, difficulty in concentrating, confusion, disturbed sleep, tingling of extremities, numbness of the tongue Skin: Increased sweating, rash, alopecia Digestive: Vomiting, borborygmi, nausea, bloating, flatulence General: Warm sensation, lethargy/drowsiness, depressed mood During safety studies at the recommended dosage, there were two reports of loss of consciousness, one of which also included urinary and fecal incontinence, stiffness of the upper torso and arms, post-syncopal skin pallor, post-syncopal confusion, and post-syncopal weakness (suggesting a seizure event).

<table ID="table1" width="80%"> <caption>Table 1 Incidence of Adverse Reactions &#x2265; 2%</caption> <col align="left" valign="middle" width="34%"/> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="33%"/> <thead> <tr> <th align="center" styleCode="Lrule Rrule">Reaction:</th> <th styleCode="Rrule">% Pyridostigmine N = 60</th> <th styleCode="Rrule">% Placebo N = 30</th> </tr> </thead> <tbody> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Diarrhea</td> <td styleCode="Rrule">7</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Abdominal Pain</td> <td styleCode="Rrule">7</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Dysmenorrhea</td> <td styleCode="Rrule">5</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Twitch</td> <td styleCode="Rrule">3</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Myalgia</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Dry Skin</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Urinary Frequency</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Epistaxis</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Amblyopia</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">0</td> </tr> <tr styleCode="Botrule"> <td styleCode="Lrule Rrule">Hypesthesia</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">0</td> </tr> <tr> <td styleCode="Lrule Rrule">Neck pain</td> <td styleCode="Rrule">2</td> <td styleCode="Rrule">0</td> </tr> </tbody> </table>