PYRIDOSTIGMINE Drug Interactions: What You Need to Know

INTERACTIONS Mefloquine: Additive effect on gastrointestinal tract and atrial rate. ( 7.1 ) Anticholinesterase drugs for glaucoma treatment: Additive effects. ( 7.2 ) Narcotics: Exacerbation of bradycardia possible. ( 7.3 ) Depolarizing neuromuscular blocking agents: Increased effect. ( 7.4 ) Non-depolarizing neuromuscular blocking agents: Dose may need to be increased. ( 7.4 ) Aminoglycoside antibiotics, local and some general anesthetics, anti-arrhythmic agents, and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all. ( 7.4 ) Drugs converted to pantothenic acid (e.g., dexpanthenol): Additive effect. ( 7.5 )

7.1 Mefloquine Concomitant use of mefloquine and pyridostigmine bromide may have additive effects on the gastrointestinal tract, the most common of which is loose bowels. Additive effects on the atrial rate may also occur with concomitant use of mefloquine and pyridostigmine bromide.

7.2 Other Anticholinesterase Drugs Concomitant use of anticholinesterase drugs used in the treatment of glaucoma and pyridostigmine bromide may have an additive effect that may cause or exacerbate problems with night vision.

7.3 Narcotics The bradycardia associated with the use of narcotics may exacerbate pyridostigmine-induced bradycardia.

7.4 Drugs that Interfere with Neuromuscular Transmission Particular caution should be observed in the administration of depolarizing neuromuscular blocking agents (e.g., succinylcholine) during surgery since the degree of neuromuscular blockade that ensues may be enhanced by previously administered pyridostigmine bromide. Doses of nondepolarizing neuromuscular blocking agents (e.g., pancuronium bromide) may need to be increased in patients previously administered pyridostigmine bromide. Atropine antagonizes the muscarinic effects of pyridostigmine bromide, and this interaction is utilized to counteract the muscarinic symptoms of pyridostigmine bromide toxicity. Anticholinesterase agents are sometimes effective in reversing neuromuscular block induced by aminoglycoside antibiotics. However, aminoglycoside antibiotics, local and some general anesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, during treatment with pyridostigmine bromide.

7.5 Drugs Converted to Pantothenic Acid Concomitant use of drugs that are converted to pantothenic acid in vivo (e.g., dexpanthenol) and pyridostigmine bromide may have additive effects by increasing production of acetylcholine.

Pyridostigmine bromide extended-release tablets are contraindicated in patients with: Mechanical intestinal or urinary obstruction Known hypersensitivity to pyridostigmine or other anticholinesterase agents Mechanical intestinal or urinary obstruction. ( 4 ) Known hypersensitivity to pyridostigmine or other anticholinesterase agents. ( 4 )

AND PRECAUTIONS At the first sign of soman poisoning, pyridostigmine must be stopped, and 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 Risk of Improper Use of Pyridostigmine Bromide Risk of Not Stopping Pyridostigmine Bromide and Using Atropine and Pralidoxime in the Event of Soman Exposure Pyridostigmine bromide is for use as pretreatment for exposure to soman nerve agent and must not be taken after exposure to soman nerve agent <span class="opacity-50 text-xs">[see Dosage and Administration (2.1 , 2.2) ]</span>. Pyridostigmine bromide 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. Discontinue pyridostigmine at the first sign of nerve agent poisoning because it may exacerbate the effects of a sublethal exposure to soman if taken immediately before exposure (e.g., when the gas attack alarm is given) or at the same time as poisoning by soman <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.2) ]</span> . Signs of nerve agent poisoning can include runny nose; watery eyes; small, pinpoint pupils; eye pain; blurred vision; drooling and excessive sweating; cough; chest tightness; rapid breathing; diarrhea; increased urination; confusion; drowsiness; weakness; headache; nausea, vomiting, and/or abdominal pain; slow or fast heart rate; and/or abnormally low or high blood pressure. Risk of Not Wearing Protective Garments Pyridostigmine bromide is not the primary protection against exposure to soman nerve agent. The 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 bromide and on the antidotes, atropine and pralidoxime (2-PAM), to provide complete protection from poisoning by soman nerve agent.

5.2 Increased Risk of Anticholinergic Adverse Reactions in Individuals with Certain Conditions Pulmonary Conditions Drugs that increase cholinergic activity, including pyridostigmine bromide, should be used with caution in persons with bronchial asthma or chronic obstructive pulmonary disease.

Cardiovascular Conditions

Because pyridostigmine bromide increases cholinergic activity, it may have vagotonic effects on heart rate, which can lead to bradycardia or cardiac arrhythmias.

Genitourinary

Tract or Gastrointestinal Tract Obstruction Drugs that increase cholinergic agents, including pyridostigmine bromide, could cause symptoms in persons susceptible to genitourinary tract or gastrointestinal tract obstruction.

Conditions

Treated with Beta Adrenergic Receptor Blockers Pyridostigmine bromide should be used with caution in people being treated for hypertension or glaucoma with beta adrenergic receptor blockers [see Drug Interactions (7.2) ].

5.3 Use in Bromide-Sensitive Individuals Caution should be taken when administering pyridostigmine bromide to individuals with known bromide sensitivity. As with any compound containing bromide, a skin rash may be observed in bromide-sensitive patients, which usually subsides promptly upon discontinuance of the medication. The risks and benefits of administration must be weighed against the potential for rash or other adverse reactions in these individuals.

5.4 Serious Adverse Reactions, Such as Difficulty Breathing, Severe Dizziness, Loss of Consciousness Pyridostigmine bromide can cause serious adverse reactions such as difficulty breathing, severe dizziness, or loss of consciousness. If these adverse reactions occur, patients should temporarily discontinue use of pyridostigmine bromide and seek immediate medical attention. Personnel should report serious adverse events to their commander and responsible medical officer.