What is the safe dosage and administration of neostigmine (acetylcholinesterase inhibitor) for myasthenia gravis?

Neostigmine Dosing for Myasthenia Gravis

For myasthenia gravis, pyridostigmine starting from 30 mg orally up to 600 mg daily is the first-line acetylcholinesterase inhibitor, with neostigmine reserved for situations where oral administration is not possible, using a conversion of 30 mg oral pyridostigmine = 1 mg IV neostigmine or 0.75 mg IM neostigmine. 1

Oral Pyridostigmine as Primary Treatment

• Pyridostigmine is the standard acetylcholinesterase inhibitor for myasthenia gravis, with dosing ranging from 30 mg to 600 mg daily in divided doses 1
• The typical dosing regimen involves multiple daily doses to maintain consistent symptom control throughout the day 1

Neostigmine Conversion and Administration

When to Use Neostigmine

• Neostigmine is indicated when oral administration is compromised or not possible, such as in patients with severe bulbar symptoms or those approaching end of life 2
• In myasthenic crisis, pyridostigmine may be discontinued or withheld, particularly if intubation is required 1

Dosing Equivalents

• 30 mg oral pyridostigmine = 1 mg IV neostigmine = 0.75 mg IM neostigmine 1
• This conversion allows for appropriate dose adjustment when switching between formulations

Alternative Routes

• Intranasal neostigmine has been shown effective with onset in 5-15 minutes, peaking at 18-33 minutes, and lasting over 2 hours 3, 4
• Intranasal administration (4.6 mg per puff) provides rapid effect for breakthrough symptoms or when oral absorption is unreliable 3
• Continuous subcutaneous infusion of neostigmine is a viable option when enteral administration is no longer possible, particularly in palliative care settings 2

Special Considerations in Myasthenia Gravis

Baseline Neuromuscular Assessment

• Evaluate the TOF ratio by EMG before administering any muscle relaxants in myasthenic patients 1
• If the TOF ratio is <0.9 before neuromuscular blockade, sensitivity to muscle relaxants is significantly increased and doses must be reduced by 50-75% 1

Drug Interactions

• Neostigmine may interfere with pyridostigmine bioavailability when both drugs are administered concurrently orally 5
• This interaction should be considered when managing patients on combination therapy

Management During Crisis

• Current guidelines recommend discontinuation of pyridostigmine during myasthenic crisis with treatment focused on IVIG or plasmapheresis 6
• However, continuous IV infusion of pyridostigmine or neostigmine can serve as a substitute when IVIG or plasmapheresis are unavailable, though cardiac arrhythmia and pneumonia are potential complications 6
• Sugammadex is preferred over neostigmine for reversal of steroidal muscle relaxants in myasthenic patients to avoid interference with long-term acetylcholinesterase inhibitor therapy 1

Critical Pitfalls to Avoid

• Never use neostigmine dosing guidelines intended for anesthetic reversal (40-70 mcg/kg IV) 1, 7 when treating myasthenia gravis—these are completely different clinical contexts with different dosing requirements
• Do not abruptly withdraw acetylcholinesterase inhibitors as this can trigger myasthenic crisis and rapid clinical deterioration 2
• Undertreated myasthenia gravis can mimic dying, particularly in patients with complex comorbidities—always consider this as a reversible cause of acute deterioration 2
• Monitor for cardiac complications when using neostigmine, particularly in crisis situations where arrhythmias may occur 6