Section 07 · Monograph

Pyridostigmine

Reviewed Nov 2026FDA label

MestinonAChE inhibitor

Indications

Symptomatic treatment of myasthenia gravis (ocular, generalized, and juvenile forms) to improve neuromuscular transmission and muscle strengthFDA-labeled
First-line agent for mild-to-moderate MG symptom control, often combined with immunosuppressive/immunomodulatory therapy for moderate-severe diseaseFDA-labeled
Pyridostigmine bromide 30 mg tablets are separately FDA-approved as pretreatment against soman (nerve agent) poisoning in military personnelFDA-labeled
Injectable pyridostigmine indicated for reversal of nondepolarizing neuromuscular blocking agents after surgeryFDA-labeled

Adjunct symptomatic therapy in Lambert-Eaton myasthenic syndrome (less effective than in MG since the defect is presynaptic)Off-label
Neurogenic orthostatic hypotension to raise standing blood pressure without worsening supine hypertensionOff-label

Reversible, competitive inhibitor of acetylcholinesterase; prevents hydrolysis of acetylcholine at the neuromuscular junction, increasing ACh availability
In MG, autoantibody-mediated loss of functional AChRs reduces the safety margin of neuromuscular transmission; boosting synaptic ACh compensates for this deficit
Quaternary ammonium compound with poor blood-brain barrier penetration, limiting central cholinergic effects
Longer duration of action and milder muscarinic side-effect profile than neostigmine, making it preferred for chronic oral MG therapy
No disease-modifying or immunosuppressive effect — purely symptomatic

MG, oral immediate-release: usual adult dose 60 mg every 3-4 hours while awake; individualize to symptom pattern — typical total daily dose 150-600 mg
MG, extended-release (Mestinon TIMESPAN 180 mg): 1-3 tablets given once or twice daily, at least 6 hours apart, typically at bedtime for overnight/early-morning weakness
Dosing is highly individualized — titrate to the lowest dose achieving adequate strength while avoiding cholinergic side effects
Injectable (IM/IV) conversion for patients unable to take oral medication: approximately 1/30th of the oral dose

Known hypersensitivity to pyridostigmine bromide or other cholinesterase inhibitors
Mechanical intestinal obstruction
Mechanical urinary tract obstruction

Atropine and other antimuscarinics can mask early muscarinic signs of cholinergic excess, risking unrecognized progression to cholinergic crisis
Additive toxicity with other cholinesterase inhibitors
Antagonizes and unpredictably interacts with neuromuscular blocking agents used in anesthesia
Aminoglycosides and certain fluoroquinolones may antagonize pyridostigmine's effect and worsen MG weakness
Beta-blockers may mask cholinergic bradycardia
Magnesium salts can antagonize neuromuscular transmission and worsen MG symptoms

Muscarinic/GI: nausea, vomiting, diarrhea, abdominal cramping, excessive salivation and bronchial secretions
Miosis, increased sweating, lacrimation
Bradycardia and, less commonly, hypotension
Nicotinic/neuromuscular: muscle cramps, fasciculations, and paradoxical weakness at high doses
Bronchospasm/increased airway secretions
Skin rash attributed to the bromide moiety
Overdose produces cholinergic crisis: profound weakness, respiratory failure, miosis, and copious secretions

Serial clinical assessment of muscle strength (e.g., MG-ADL, quantitative MG score) to guide titration
Watch for signs of cholinergic excess versus undertreatment/myasthenic weakness — critical to differentiate myasthenic crisis from cholinergic crisis
Respiratory status (vital capacity, negative inspiratory force) in patients with bulbar or respiratory muscle involvement
Renal function periodically, especially in older adults
Bowel/bladder function for signs of obstruction

Safety in human pregnancy and lactation has not been formally established in controlled trials
As a quaternary ammonium compound, placental transfer is limited but not absent; case reports describe use throughout pregnancy in MG patients without a clear teratogenic signal
Untreated/undertreated MG poses its own maternal and fetal risks, so therapy is often continued in pregnancy under specialist supervision
Limited data suggest transfer into breast milk is low; monitor breastfed infants for cholinergic symptoms if maternal doses are high