What is the average dose of oral neostigmine (acetylcholinesterase inhibitor) tablets?

Oral Neostigmine Dosing for Myasthenia Gravis

For oral neostigmine tablets in myasthenia gravis, the typical dosing range is 15-480 mg per day, divided into multiple doses, though pyridostigmine is the preferred oral anticholinesterase agent. 1

Clinical Context and Dosing Framework

Oral neostigmine is rarely used as first-line therapy for myasthenia gravis in modern practice. When it is prescribed:

• The documented therapeutic range in clinical studies spans 15-480 mg daily, administered in divided doses throughout the day 1
• Plasma concentrations of 5-15 ng/ml appear to provide maximal therapeutic effect, with a "bell-shaped" dose-response curve suggesting that higher doses may paradoxically reduce efficacy 2
• Pyridostigmine is generally preferred over oral neostigmine for chronic myasthenia management due to more predictable pharmacokinetics and better tolerability 1, 2

Important Dosing Considerations

Starting and Titration Strategy

• Begin with lower doses (15-30 mg) and titrate upward based on clinical response, as there is substantial inter-patient variability in bioavailability 1
• Avoid concurrent administration of neostigmine and pyridostigmine, as neostigmine may interfere with pyridostigmine bioavailability when both drugs are given orally 1

Alternative Routes for Specific Situations

• Intranasal neostigmine provides rapid onset (5-15 minutes) and may be beneficial for patients with irregular oral absorption, early morning weakness, or bulbar impairment 3
• The conversion ratio is approximately 30 mg oral pyridostigmine = 1 mg IV neostigmine = 0.75 mg IM neostigmine 4

Critical Pitfalls to Avoid

• Excessive dosing can cause paradoxical muscle weakness due to depolarizing neuromuscular blockade, as demonstrated by the bell-shaped dose-response curve 2
• Monitor for cholinergic side effects including bradycardia, increased secretions, and gastrointestinal symptoms, which may necessitate dose reduction
• Individual plasma concentrations vary up to seven-fold even among patients on identical daily doses, requiring individualized clinical monitoring rather than rigid dose protocols 2

Monitoring Parameters

• Clinical response should be assessed by objective muscle strength testing (e.g., grip strength, vital capacity) rather than plasma levels alone 2
• Electromyographic assessment of decremental response in deltoid or other muscles can guide dose optimization 2