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Class: Parasympathomimetic (Cholinergic) Agents
- Anticholinesterase Agents
VA Class: AU300
CAS Number: 101-26-8
Brands: Mestinon, Regonol

Medically reviewed by Last updated on May 18, 2020.


    Military Use for Soman Poisoning Prophylaxis
  • Use of pyridostigmine alone is not protective against soman effects.111 Efficacy depends on rapid use of nerve agent antidotes (i.e., atropine and pralidoxime) following nerve agent exposure.111

  • Protective garments (e.g., masks, hoods, overgarments) specifically designed for protection from chemical nerve agents are the primary means of protection against nerve agent exposure; do not rely solely on pretreatment with pyridostigmine, atropine, and pralidoxime to provide complete protection.111

  • Do not administer pyridostigmine after soman exposure.111 Discontinue at first sign of nerve agent poisoning; may exacerbate effects of a sublethal exposure.111

    Experience of Health Care Personnel
  • Pyridostigmine should be administered by IV injection only by adequately trained individuals familiar with the drug’s actions, characteristics, and risks.124


Reversible anticholinesterase agent.a 123 124 111

Uses for Pyridostigmine

Myasthenia Gravis

Symptomatic management of myasthenia gravis to improve muscle strength.123 127 128 206 a

Following oral administration of a conventional preparation, onset of effect occurs within about 15–30 minutes and duration is about 3–4 hours.127 206

Experts state that pyridostigmine should be part of the initial treatment in most patients with myasthenia gravis.128 Although symptomatic improvement can usually be achieved, additional treatment with corticosteroids or other immunosuppressive agents may be required.127 128 206

Reversal of Neuromuscular Blockade

Reversal of the effects of nondepolarizing neuromuscular blocking agents (e.g., atracurium, cisatracurium, pancuronium, rocuronium, vecuronium).a 124 126 220

Use in conjunction with an anticholinergic agent (atropine sulfate or glycopyrrolate) to counteract adverse muscarinic effects (e.g., bradycardia, bradyarrhythmias, increased secretions, bronchoconstriction).124 220 221

Not effective and should not be used for reversal of depolarizing neuromuscular blocking agents (e.g., succinylcholine).124 a

Chemical Warfare Agent Poisoning

Preexposure prophylaxis against lethal effects of soman nerve agent poisoning in military combat personnel.111 116

Used in conjunction with standard treatment of nerve agent poisoning (i.e., atropine and pralidoxime chloride) and other protective measures (e.g., masks, hoods, overgarments).111

Discontinue use at first indication of nerve agent poisoning.111 Not for use after exposure to soman; not expected to be effective after such exposure and may exacerbate effects of sublethal exposure.111 (See Military Use for Soman Poisoning Prophylaxis in Boxed Warning.)

Pyridostigmine Dosage and Administration


Myasthenia Gravis

  • Individualize dosage and frequency of administration.a Minimize adverse effects with precise dosage adjustment.a

  • Dosage requirements may vary from day to day, according to remissions and exacerbations of the disease and physical and emotional condition of the patient.a

  • Treat mild exacerbations by increasing dosage under medical supervision as long as increase produces symptomatic improvement.a

  • Complete restoration of muscle strength is rare; do not attempt to relieve all symptoms by increasing dosage above maximum response level.a

  • Individual muscle groups may respond differently to the same dose; may produce weakness in one while increasing strength in another.a

Reversal of Neuromuscular Blockade

  • Administer only by trained clinicians experienced in the use of neuromuscular blocking agents and their reversal agents.124

  • Always have atropine and medications to treat shock readily available in case of hypersensitivity reaction.124

  • Administer an anticholinergic agent (e.g., atropine sulfate) in conjunction with pyridostigmine to counteract adverse muscarinic effects (e.g., excessive secretions, bradycardia).124 220 221

  • Monitor muscle twitch response to peripheral nerve stimulation; administer pyridostigmine after spontaneous recovery of neuromuscular function begins.124 Satisfactory reversal is evident by adequate voluntary respiration, respiratory measurements, and use of a peripheral nerve stimulator device.124

  • Patient must be well ventilated; maintain patent airway and manual or mechanical ventilation until complete recovery of normal respiration is assured.124 Recurrence of paralysis unlikely after satisfactory reversal attained.124

Chemical Warfare Agent Poisoning

  • Administer orally prior to an expected exposure to soman (i.e., when under the threat of a nerve agent attack).111 Do not take after exposure to soman.111

  • If taken immediately before or at the same time as soman poisoning, pyridostigmine is not likely to be effective and may exacerbate the effects of a sublethal exposure.111


Administer orally or by IV injection.123 124 Also has been administered by IM injection,a 125 but manufacturer of currently available injectable preparation states that this injection is for IV use only.124

Oral Administration

Administer orally (as conventional tablets, extended-release tablets, or oral solution).123

Oral solution may be useful for children and other patients who have difficulty swallowing or who require precise dosage adjustments not possible with tablets.a 123

Extended-release tablets (Mestinon Timespan) are designed to slowly release drug for a prolonged duration of action; the immediate effect of a 180-mg extended-release tablet is similar to that of a 60-mg conventional tablet, but duration is about 2.5 times longer.123 Extended-release tablets generally used only at bedtime for patients who awaken at night or in the early morning with impairing weakness.127 206 May use extended-release tablets concurrently with conventional preparations to achieve optimum control.123

NG Tube

May administer oral solution through nasogastric tube.a

IV Administration

Administer by IV injection.124 a (See General under Dosage and Administration.)


Pediatric Patients

Myasthenia Gravis

Neonates: 5 mg every 4–6 hours has been used.a 125 (See Pediatric Use under Cautions.)

Children: 7 mg/kg daily (administered in 5–6 divided doses) has been used.a 125 129 (See Pediatric Use under Cautions.)

IV or IM

Neonates: 0.05–0.15 mg/kg (maximum single dose of 10 mg) every 4–6 hours has been used.a 125 (See Pediatric Use under Cautions.)

Children: 0.05–0.15 mg/kg (maximum single dose of 10 mg) every 4–6 hours has been used.125 (See Pediatric Use under Cautions.)


Myasthenia Gravis

Initiate with low dosage (usually 60 mg 3 times daily as conventional tablets or oral solution).a May gradually increase as needed at intervals of ≥48 hours to provide maximum relief of symptoms.a

Adjust dosage of conventional tablets or oral solution so larger doses are taken at times of greatest fatigue (e.g., 30–45 minutes before meals to assist patients who have difficulty eating).a 123

Usual daily maintenance dosage ranges from 60 mg to 1.5 g (average 600 mg).a 123

Extended-release tablets: Manufacturer suggests dosage of 180–540 mg 1–2 times daily (with ≥6 hours between doses).a 123 However, extended-release dosage form is generally used only at bedtime in patients who awaken at night or in the early morning with impairing weakness.a

Oral dosage changes may take several days to produce results.a When a further increase in dosage produces no corresponding increase in muscle strength, reduce dosage to the previous level.a

Dosage requirements may vary from day to day.a

IV or IM

When administered parenterally, approximately 1/30 of usual oral dose has been given by IM or very slow IV injection; however, currently available parenteral preparation (Regonol) not FDA-labeled for treatment of myasthenia gravis.124 a

Reversal of Neuromuscular Blockade

0.1–0.25 mg/kg.124 Give concurrently with or immediately after 0.6–1.2 mg IV atropine sulfatea 124 (or an equipotent dose of glycopyrrolate).124

Full recovery usually occurs within 15 minutes but may require ≥30 minutes.124

Additional doses of pyridostigmine not recommended if reversal is inadequate; instead, manage with manual or mechanical ventilation until adequate recovery occurs.124

Chemical Warfare Agent Poisoning
Preexposure Prophylaxis for Soman Poisoning

30 mg every 8 hours beginning several hours prior to anticipated exposure.111

Discontinue at first sign of nerve agent poisoning; immediately treat with atropine and pralidoxime.111

Effects of use for >14 consecutive days not established; evaluate continuation of prophylaxis based on likelihood of exposure to soman.111

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.111 a 123 124

Renal Impairment

Lower dosages may be required; carefully titrate dosage.123

Geriatric Patients

Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.111

Cautions for Pyridostigmine


  • Known hypersensitivity to anticholinesterase agents.111 a 124

  • Mechanical obstruction of the intestinal or urinary tract.a 111 123 124



Cholinergic Crisis

Overdosage may result in cholinergic crisisa 123 (e.g., excessive salivation and sweating, miosis, nausea, vomiting, diarrhea, bradycardia or tachycardia, hypotension or hypertension, confusion, seizures, coma, severe muscle weakness, paralysis);a may result in death.123 If overdosage occurs, maintain adequate respiration and give IV atropine.a

Myasthenic crisis due to increased disease severity also causes extreme muscle weakness; symptomatic differentiation from cholinergic crisis may be difficult.a 123 Time to onset of symptoms approximately 1 hour after dose suggests overdosage, while ≥3 hours after dose suggests underdosage or resistance is the more likely diagnosis.a

If severe cholinergic reaction occurs, discontinue pyridostigmine immediately and institute appropriate therapy as indicated (e.g., atropine, medications to treat shock).a 124

Excessive IV doses may produce depolarization block when administered at doses above therapeutic range to reverse nondepolarizing neuromuscular blocking agent effects.124 Therapeutic index (ratio of reversal dose to blocking dose) is approximately 1:6.124

Concomitant Diseases

Use with caution in patients with bronchial asthma, COPD, bradycardia, or cardiac arrhythmias.a 124 111

Preexposure Prophylaxis for Soman Poisoning

Do not administer pyridostigmine after soman exposure.111 Discontinue at first sign of nerve agent poisoning; may exacerbate effects of a sublethal soman exposure.111 (See Boxed Warning.)

Military personnel experiencing severe adverse effects (e.g., difficulty breathing, severe dizziness, loss of consciousness) associated with pyridostigmine use should temporarily discontinue the drug and immediately seek medical care.111

Sensitivity Reactions

Bromide Sensitivity

Use caution in patients with known bromide sensitivity.111

May cause skin rash, which usually disappears when pyridostigmine bromide is discontinued.a 111 123 124

General Precautions

Electrolyte Imbalance

Conditions resulting in electrolyte imbalance (e.g., adrenocortical insufficiency) may alter neuromuscular blockade (enhance or inhibit) and interfere with postoperative restoration of neuromuscular function by pyridostigmine.124

Specific Populations


Safety during pregnancy not established.111 124 Risk of uterine irritability and induction of premature labor if anticholinesterase agents are given IV near term.a

Category B (30-mg tablets for military use only).111


Not known whether pyridostigmine is distributed into milk.111 Safety during lactation not established.124 Caution advised if used in nursing women.111

Pediatric Use

Although manufacturers state safety and efficacy not established in pediatric patients,111 123 124 has been used for treatment of juvenile myasthenia gravis.125 128 129

Pyridostigmine bromide injection (e.g., Regonol) contains 1% benzyl alcohol.124 Manufacturer does not recommend use in neonates;124 AAP states that the presence of small amounts of this preservative in a commercially available injection should not proscribe its use when indicated in neonates.103 Consider combined daily intake of benzyl alcohol from all sources.124

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.111

Substantially eliminated by the kidneys; may be useful to monitor renal function since geriatric patients are more likely to have decreased renal function.111

Renal Impairment

Use with caution.111 Clearance may be decreased; dosage adjustments necessary in renal disease.123 (See Renal Impairment under Dosage and Administration.)111

Common Adverse Effects

Diarrhea,111 abdominal pain or cramps,111 116 dysmenorrhea,111 increased flatus,116 nausea,116 urinary urgency and frequency.116

Interactions for Pyridostigmine

Specific Drugs




Aminoglycosides (e.g., gentamicin, neomycin, streptomycin)

Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124

Use cautiously, if at all111

Anesthetics, local or general

Interfere with neuromuscular transmissiona

Use cautiously, if at alla

Antiarrhythmic agents

Interfere with neuromuscular transmissiona

Use cautiously, if at alla


Antagonizes muscarinic effects of pyridostigminea 111

Interaction used to therapeutic advantage to counteract muscarinic symptoms of pyridostigmine toxicity; however,111 atropine also may mask manifestations of pyridostigmine overdose and prevent early detection of cholinergic crisisa 123


Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124

β-Adrenergic blocking agents

Possible additive bradycardiae

Possible inhibition of pyridostigmine efficacy in myasthenia gravise

Use concomitantly with caution; 111 effects on patients with borderline heart failure or AV conduction disturbances not determined118

Magnesium salts

Possible enhanced neuromuscular blockade124

Consider possibility of interference with restoration of neuromuscular function by pyridostigmine124


Possible additive GI effects111

Possible additive effects on atrial rate111

Miotics, topical (e.g., physostigmine)

Possible additive effects; may cause or exacerbate problems with night visiona 111

Neuromuscular blocking agents, depolarizing (e.g., succinylcholine)

Possible enhanced and/or prolonged neuromuscular blockade111 a

Do not use for reversal of depolarizing neuromuscular blockadea

When pyridostigmine is used for nerve agent prophylaxis in soldiers, use caution if a depolarizing neuromuscular blocking agent is administered during surgery111 117

Neuromuscular blocking agents, nondepolarizing (e.g., atracurium, cisatracurium, pancuronium, rocuronium, vecuronium)

Antagonism of nondepolarizing muscle relaxant effectsa

Interaction used to therapeutic advantage to reverse muscle relaxation induced by neuromuscular blocking agents after surgerya

May need to increase dosage of nondepolarizing agent in soldiers who received pyridostigmine111

Opiate agonists

Possible exacerbation of pyridostigmine-induced bradycardia111

Polymyxins (e.g., colistin, polymyxin B, sodium colistimethate)

Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124


Recurrent paralysis may occur if used in conjunction with nondepolarizing neuromuscular blocking agents124


Possible prolongation of neuromuscular blockade or resistance to reversal if used in conjunction with nondepolarizing neuromuscular blocking agents124

Pyridostigmine Pharmacokinetics



Poorly absorbed from GI tract following oral administration;a bioavailability is 10–20%.101 111 115

Peak plasma concentrations occur 2.2 hours after oral ingestion of a 30-mg dose as conventional tablet.111

Extended-release tablets reportedly release one-third of total dose immediately, then remainder over 8–12 hours; however, release may be erratic and unpredictable.a


Following oral administration in patients with myasthenia gravis, 30–45 minutes.a

Following IV injection in patients with myasthenia gravis, muscle strength increased in 2–5 minutes.a

When used for postoperative reversal of nondepolarizing neuromuscular blocking agent effects, time to peak effect is dose-dependent; with 0.25-mg/kg dosage, return of twitch height to 90% of control occurs within about 6 minutes.124 At lower dosages, full recovery usually occurs within 15 minutes; may require ≥30 minutes in some patients.124


Duration of effect varies in patients with myasthenia gravis.a Effects generally persist for 3–6 hours for conventional oral tablets, about 8–12 hours for extended-release tablets, and about 2–3 hours for IV injection.a



Distributed into most tissues, except brain, intestinal wall, fat, and thymus.a

Crosses the placenta;a not known whether distributed into milk.a 111



Metabolized via hydrolysis by cholinesterases and by microsomal enzymes in the liver.a 111

Elimination Route

Excreted in urine, principally as unchanged drug (80–90%).100 101 102


Conventional oral tablets: 3 hours.100 101 102 110 111

IV: 1.05–1.86 hours.100 101 102 110

Special Populations

Patients with severe myasthenia gravis metabolize and excrete pyridostigmine faster than patients with milder forms of the disease.a

Anephric patients: Half-life 6.3 hours;102 clearance decreased by 75%.111

Geriatric patients (71–85 years of age): Plasma clearance decreased 30%, but half-life is unchanged.111

No information available on pyridostigmine pharmacokinetics in patients with hepatic impairment.111




Conventional 60-mg Tablets and Extended-release Tablets

25°C (may be exposed to 15–30°C).123

Extended-release tablets are hygroscopic; tablets may become mottled, but this does not affect potency.123

Conventional 30-mg Tablets for Military Use

2–8°C; protect from light.111 Discard unrefrigerated unit-dose packages after 3 months.111

Oral Solution

25°C (may be exposed to 15–30°C).123



25°C (may be exposed to 15–30°C).124 Protect from light.124


  • Analog of neostigmine, but pyridostigmine may have a longer duration of action and fewer adverse GI effects.a 123 124

  • Reversibly inhibits acetylcholinesterase, thereby prolonging and exaggerating the effects of acetylcholine.111 117 118 120 121 a Has direct cholinomimetic effect on skeletal muscle.a

  • Produces generalized cholinergic responses including miosis, bradycardia, increased tonus of intestinal musculature, constriction of bronchi and ureters, and stimulation of secretion by salivary and sweat glands.a

  • At sufficiently high dosage, directly blocks action at autonomic ganglia, causes CNS stimulation followed by CNS depression, and, ultimately, depolarization block.a

  • Blocks nerve agent soman from access to acetylcholinesterase active sites, protecting the enzyme from irreversible inhibition.111 117

Advice to Patients

  • Patients with myasthenia gravis: importance of carefully following prescribed dosage instructions.123

  • Advise military personnel to take pyridostigmine as directed by chain of command for preexposure prophylaxis for possible soman poisoning; advise not to take pyridostigmine immediately before (when attack alarm is given), during, or after exposure to soman.111 Importance of discontinuing pyridostigmine and following instructions provided in pyridostigmine patient information for treatment (e.g., atropine, pralidoxime) if soman poisoning occurs.111 Advise military personnel that if they experience serious adverse effects (e.g., difficulty breathing, severe dizziness, loss of consciousness), to temporarily discontinue the drug and immediately seek medical care.111 Advise such individuals that pyridostigmine alone is not protective against soman poisoning; the primary means of protection against nerve agent exposure is wearing protective garments (e.g., masks, hoods, overgarments) designed for this use.111 Importance of discarding 30-mg tablets 3 months after date of issue.111

  • Importance of informing clinician of any allergy to bromide or anticholinesterase drugs.111

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.123 124

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.123 124

  • Importance of informing patients of other important precautionary information.123 124 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Pyridostigmine bromide 30-mg immediate-release tablets are for military use only.111

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Pyridostigmine Bromide


Dosage Forms


Brand Names




60 mg/5 mL

Mestinon Oral Solution


Tablets, immediate-release

60 mg*

Mestinon (scored)


Pyridostigmine Bromide Tablets

Tablets, extended-release

180 mg*

Mestinon Timespan (scored)


Pyridostigmine Bromide Extended-release Tablets



5 mg/mL



AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 18, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


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e. Stockley IH, editor. Stockley's drug interactions. 6th edition. Chicago, IL: Pharmaceutical Press; 2002.