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Medically reviewed by Last updated on Nov 7, 2020.


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Index Terms

  • Pyridostigmine Bromide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as bromide:

Regonol: 10 mg/2 mL (2 mL) [contains benzyl alcohol]

Solution, Oral, as bromide:

Mestinon: 60 mg/5 mL (473 mL) [contains alcohol, usp, brilliant blue fcf (fd&c blue #1), fd&c red #40, sodium benzoate; raspberry flavor]

Generic: 60 mg/5 mL (5 mL, 473 mL)

Tablet, Oral, as bromide:

Mestinon: 60 mg [scored]

Generic: 30 mg, 60 mg

Tablet Extended Release, Oral, as bromide:

Mestinon: 180 mg [scored]

Generic: 180 mg

Brand Names: U.S.

  • Mestinon
  • Regonol

Pharmacologic Category

  • Acetylcholinesterase Inhibitor


Inhibits destruction of acetylcholine by acetylcholinesterase which facilitates transmission of impulses across neuromuscular junction


Oral: Very poor (10% to 20%)


Vd: 0.53 to 1.76 L/kg (Aquilonius 1986)


Hepatic and at tissue site by cholinesterases


Urine (80% to 90% as unchanged drug) (Aquilonius 1986)

Onset of Action

Recovery from vincristine neurotoxicity: Onset of action: 1 to 2 weeks (Akbayram 2010)

Myasthenia gravis: Oral: Within 30 minutes (Maggi 2011); IM: 15 to 30 minutes; IV: Within 2 to 5 minutes

Time to Peak

Oral: 1 to 2 hours (Aquilonius 1986)

Duration of Action

Oral: 3 to 4 hours in the daytime (Maggi 2011); IM, IV: 2 to 3 hours

Half-Life Elimination

Oral: 1 to 2 hours; renal failure: ~6 hours (Aquilonius 1986)

IV: ~1.5 hours (Aquilonius 1980)

Protein Binding

None (Aquilonius 1986)

Use: Labeled Indications

Myasthenia gravis (oral only): Treatment of myasthenia gravis.

Reversal of nondepolarizing muscle relaxants (injection only): Reversal agent or antagonist to the neuromuscular blocking effects of nondepolarizing muscle relaxants.

Military use: Pretreatment for Soman nerve gas exposure

Off Label Uses

Disopyramide-induced anticholingeric adverse effects

Data from a double-blind, randomized crossover study in patients treated with disopyramide supports the use of sustained-release pyridostigmine to mitigate anticholinergic adverse effects (eg, urinary retention, constipation, dry mouth) associated with the use of disopyramide without affecting its electrophysiologic or antiarrhythmic properties [Teichman 1987]. Clinical experience also suggests the utility of pyridostigmine for this purpose [Sherrid 2016], [Verlinden 2015].

Myasthenia gravis (IM, IV use)

Clinical experience suggests the utility of IM or IV pyridostigmine in managing this condition [Maggi 2011]. A continuous infusion has been employed for some patients experiencing myasthenic crisis [Berrouschot 1997], [Saltis1993]. Additional data may be necessary to further define the role of pyridostigmine in this condition.


Hypersensitivity to pyridostigmine, anticholinesterase agents, or any component of the formulation; mechanical intestinal or urinary obstruction

Documentation of allergenic cross-reactivity for anticholinergic muscle stimulants is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Myasthenia gravis:

Oral: Highly individualized dosing ranges:

Immediate-release: 60 to 1,500 mg/day, usually 600 mg/day divided into 5 to 6 doses, spaced to provide maximum relief

Sustained release: 180 to 540 mg once or twice daily (doses separated by at least 6 hours); Note: It may be necessary to use immediate-release therapy in conjunction with sustained-release therapy.

IM, IV (off-label use): To supplement during labor and postpartum, during myasthenic crisis, or when oral therapy is impractical: ~1/30th of oral dose; observe patient closely for cholinergic reactions. IM route preferred due to significant complications (eg, cardiac arrest) observed with the IV route (Maggi 2011; Varner 2013). May also administer as a continuous infusion for myasthenic crisis.

Continuous infusion: IV: 1 to 2 mg/hour with gradual titration in increments of 0.5 to 1 mg/hour, up to a maximum rate of 4 mg/hour (Berrouschot 1997; Saltis 1993)

Reversal of nondepolarizing muscle relaxants: IV: 0.1 to 0.25 mg/kg/dose (onset to peak effect is dose-dependent; return of twitch height to 90% of control occurs within ~6 minutes; full recovery usually occurs within 15 to 30 minutes)

Note: The monitoring of muscle twitch response to peripheral nerve stimulation is advised; administer pyridostigmine after spontaneous recovery of neuromuscular function has begun. Atropine sulfate or glycopyrrolate IV should be administered immediately prior to or simultaneously with pyridostigmine to minimize side effects. Inadequate reversal is possible; manage by manual or mechanical ventilation until recovery is judged adequate (additional doses are not recommended).

Soman nerve gas exposure, pretreatment (military use): Note: Do not administer pyridostigmine after Soman exposure; if taken immediately before exposure (eg, when gas attack alarm is given) or at the same time, it is not expected to be effective and may exacerbate the effects of a sub-lethal exposure to Soman.

Oral: 30 mg every 8 hours beginning several hours prior to exposure; discontinue at first sign of Soman exposure, then immediately begin atropine and pralidoxime.

Disopyramide-induced anticholingeric adverse effects (off-label use): Oral: Sustained release: 90 to 180 mg every 12 hours or as needed (Sherrid 2013; Sherrid 2016; Teichman 1987).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Myasthenic syndromes, congenital: Limited data available:

Note: Therapeutic response dependent upon inherited genetic variation and resultant type of myasthenic syndrome; pyridostigmine use should be under the supervision of a specialist experienced in the diagnosis and management of congenital myasthenic syndromes; some syndromes may be worsened by pyridostigmine therapy (eg, slow-channel myasthenic syndrome) and pyridostigmine use should be avoided (Ciafaloni 2019; Kliegman 2020). Dosage should be individualized based on patient response.

Infants, Children, and Adolescents: Oral: Immediate release: 1 mg/kg/dose every 4 hours; usual range: 4 to 5 mg/kg/day in 4 to 6 divided doses; maximum daily dose: 7 mg/kg/day divided in 5 to 6 doses (Kliegman 2020; Lorenzoni 2012).

Myasthenia gravis, autoimmune (juvenile): Limited data available: Note: Pyridostigmine usually considered part of initial treatment for most patients (MGFA [Sanders 2016]). Dosage should be adjusted such that larger doses administered prior to time of greatest fatigue.

Infants, Children, and Adolescents:

Oral: Immediate release: 0.5 to 1 mg/kg/dose every 4 to 6 hours; usual maximum single dose: 60 mg/dose; maximum daily dose: 7 mg/kg/day in divided doses (Kliegman 2020); in adults, therapeutic effects usually observed at total daily doses <960 mg/day divided into 4 to 8 doses; in some pediatric patients, doses as high as 1,500 mg/day have been reported (Andrews 1998; Kliegman 2020; Maggi 2011).

IM, IV: 0.05 to 0.15 mg/kg/dose; maximum dose: 10 mg/dose (Kliegman 2007).

Reversal of nondepolarizing neuromuscular blocker: Limited data available: Note: Pyridostigmine rarely used; other agents (eg, neostigmine, sugammadex) have routine place in therapy. Administer atropine or glycopyrrolate immediately prior to minimize side effects.

Infants, Children, and Adolescents: IM, IV: 0.1 to 0.25 mg/kg/dose (Kliegman 2007).

Vincristine-induced neurotoxicity: Very limited data available; efficacy results variable: Children ≥2 years and Adolescents: Oral: Immediate release: 3 mg/kg/day divided in 2 doses, in combination with pyridoxine for 3 weeks; dosing based on a case series of 4 children (age: 2 to 13 years) receiving vincristine for treatment of acute lymphoblastic leukemia (Akbayram 2010) and a 2-year-old receiving vincristine for a cervical synovial sarcoma (Müller 2004).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.


Myasthenic crisis (off-label use): Continuous infusion: May dilute 25 mg in 100 mL of D5W (Saltis 1993).


Oral: Do not crush ER tablet.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER tablets should be swallowed whole. Do not break, crush, or chew. IR tablet, oral solution, syrup, and injectable formulations are available.

If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of IR pyridostigmine formulations should be strongly considered in those with severe myasthenia gravis symptoms or when using for nerve gas exposure prophylaxis.

IV: For myasthenic crisis (off-label use), may administer IM, slow IV push, or as a continuous infusion (Maggi 2011; Saltis 1993).


Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect from moisture.

Military use: Store between 2°C and 8°C (36°F to 46°F); protect from light. Discard 3 months after issue. Do not dispense after removal from the refrigerator for more than a total of 3 months.

Drug Interactions

Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Monitor therapy

Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Monitor therapy

Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Monitor therapy

Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Methocarbamol: May diminish the therapeutic effect of Pyridostigmine. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Succinylcholine: Acetylcholinesterase Inhibitors may increase the serum concentration of Succinylcholine. Management: Consider alternatives to this combination due to a risk of prolonged neuromuscular blockade. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Central nervous system: Twitching (3%), hyperesthesia (2%)

Dermatologic: Xeroderma (2%)

Gastrointestinal: Abdominal pain (7%), diarrhea (7%)

Genitourinary: Dysmenorrhea (5%), urinary frequency (2%)

Neuromuscular & skeletal: Myalgia (2%), neck pain (2%)

Ophthalmic: Amblyopia (2%)

Respiratory: Epistaxis (2%)

Frequency not defined:

Cardiovascular: Bradycardia (transient), chest tightness, decreased heart rate, increased blood pressure

Central nervous system: Confusion, depressed mood, disturbed sleep, drowsiness, headache, hypertonia, lack of concentration, lethargy, localized warm feeling, numbness of tongue, tingling of extremities, vertigo

Dermatologic: Alopecia, diaphoresis, skin rash

Gastrointestinal: Abdominal cramps, bloating, borborygmi, flatulence, increased peristalsis, nausea, salivation, vomiting

Hypersensitivity: Hypersensitivity reaction

Neuromuscular & skeletal: Fasciculations, muscle cramps, weakness

Ophthalmic: Eye pain, lacrimation, miosis, visual disturbance

Respiratory: Acute bronchitis (exacerbation), exacerbation of asthma, increased bronchial secretions

<1%, postmarketing, and/or case reports: Fecal incontinence, loss of consciousness, pallor (postsyncopal), stiffness (arms or upper torso), thrombophlebitis, urinary incontinence


Concerns related to adverse effects:

• Cholinergic effects: Symptoms of excess cholinergic activity may occur (eg, salivation, sweating, urinary incontinence). Overdosage may result in cholinergic crisis (eg, muscle weakness), which must be distinguished from myasthenic crisis; discontinue immediately in the presence of cholinergic crisis.

• Hypersensitivity reactions: May occur; have atropine and epinephrine ready to treat hypersensitivity reactions.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with bradycardia or other cardiac arrhythmias.

• Glaucoma: Use with caution; additive effect with antiglaucoma drugs may cause or exacerbate problems with night vision.

• Renal impairment: Use with caution in patients with renal impairment; initial lower doses may be needed; titrate to effect.

• Respiratory disease: Use with extreme caution in patients with asthma, bronchospastic disease, or COPD.

Special populations:

• Bromide sensitivity: Use with caution in patients with bromide sensitivity.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

• Injection: Must be administered by trained personnel; use of peripheral nerve stimulation to monitor neuromuscular function recovery and continuous patient observation until recovery of normal respiration is recommended. To counteract anticholinergic effects, use of glycopyrrolate or atropine sulfate simultaneously with or prior to administration is recommended. May contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.

• Oral: Adequate facilities should be available for cardiopulmonary resuscitation when testing and adjusting dose for myasthenia gravis.

Other warnings/precautions:

• Inadequate reversal of nondepolarizing muscle relaxants: Inadequate reversal induced by nondepolarizing muscle relaxants is possible; manage with manual or mechanical ventilation until recovery is adequate (additional doses not recommended). Failure to produce prompt (within 30 minutes) reversal of neuromuscular blockade may occur in the presence of extreme debilitation, carcinomatosis, or with concomitant use of certain broad-spectrum antibiotics, or anesthetic agents and other drugs which enhance neuromuscular blockade or cause respiratory depression.

• Military use: Only for pretreatment for exposure to Soman; discontinue pyridostigmine at the first sign of Soman exposure (do not administer pyridostigmine after Soman exposure); atropine and pralidoxime must be administered after Soman exposure (pyridostigmine pretreatment offers no benefit against Soman unless atropine and pralidoxime are administered once symptoms of poisoning appear). Use in conjunction with protective garments, including gas mask, hood and overgarments.

Monitoring Parameters

ECG, blood pressure, and heart rate especially with IV use; observe for cholinergic reactions (eg, nausea, vomiting, diarrhea, increased salivation), particularly when administered IV; consult individual institutional policies and procedures

Pregnancy Considerations

Pyridostigmine may cross the placenta (Buckley 1968).

Oral pyridostigmine is the agent of choice for treating myasthenia gravis during pregnancy; the IV route may cause uterine contractions and is not recommended (Sanders 2016). Use should be continued during labor (Norwood 2014). Transient neonatal myasthenia gravis may occur in neonates due to placental transfer of maternal antibodies (Norwood 2014; Sanders 2016).

In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003).

Patient Education

What is this drug used for?

All oral products:

• It is used to treat myasthenia gravis.


• It is used to get back function in muscles after surgery.

All products:

• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Trouble breathing

• Slow heartbeat

• Nausea

• Vomiting

• Abdominal cramps

• Diarrhea

• Drooling

• Small pupils

• Sweating a lot

• Muscle cramps

• Twitching

• Muscle weakness

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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