Can oral tablets of neostigmine be used to treat myasthenia gravis?

Oral Neostigmine Tablets for Myasthenia Gravis

Oral neostigmine tablets are not the preferred acetylcholinesterase inhibitor for myasthenia gravis—pyridostigmine bromide is the first-line oral anticholinesterase agent, administered 2-4 times daily. 1

Primary Treatment Recommendation

• Pyridostigmine bromide is the standard oral anticholinesterase for MG, not oral neostigmine, with dosing typically ranging from 30-600 mg daily in divided doses. 2, 1
• Approximately 50% of patients with ocular MG show only minimal response to anticholinesterase therapy, while the other half benefit significantly. 1
• The median effectiveness reported by patients on pyridostigmine is 60% (IQR 28-78), with 91% experiencing some side effects (most commonly flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis). 3

Why Neostigmine Is Not Used Orally

• Neostigmine interferes with pyridostigmine bioavailability when both drugs are administered orally concurrently, eliminating the predictable dose-response relationship seen with pyridostigmine alone. 4
• When myasthenic patients stabilized on pyridostigmine alone showed a direct correlation between dose and plasma levels (r=0.95), this relationship disappeared when oral neostigmine was added. 4
• The FDA label for neostigmine specifically addresses injectable formulations and warns about use in myasthenia gravis patients, noting increased cardiovascular risks. 5

Alternative Neostigmine Formulations That Work

Intranasal Neostigmine

• Intranasal neostigmine (4.6 mg per puff) provides rapid onset within 3 minutes, peaks at 18-33 minutes, and lasts over 2 hours, making it useful for breakthrough symptoms. 6
• This formulation is beneficial for: (1) patients with irregular oral absorption, (2) early morning dosing when rapid effect is needed, and (3) bulbar impairment or emergencies where a handheld atomizer may be life-saving. 7
• Clinical and electrophysiological improvement occurs within 5-15 minutes of intranasal administration. 7

Intravenous/Intramuscular Neostigmine

• For intubated MG crisis patients, pyridostigmine should be discontinued or withheld; if IV anticholinesterase is needed, 30 mg oral pyridostigmine corresponds to 1 mg IV neostigmine or 0.75 mg IM neostigmine. 2
• IV neostigmine produces marked effect immediately after injection lasting over 1 hour. 6

Critical Safety Considerations

• Neostigmine requires atropine or glycopyrrolate pre-administration to prevent bradycardia, and should be used with extreme caution in patients with coronary artery disease, cardiac arrhythmias, or recent acute coronary syndrome. 5
• The risk of differentiating myasthenic crisis from cholinergic crisis (neostigmine overdose) is significant—both cause extreme muscle weakness but require opposite treatments. 5
• Large doses when neuromuscular blockade is minimal can paradoxically produce neuromuscular dysfunction. 5

Practical Clinical Algorithm

For newly diagnosed MG:

1. Start pyridostigmine bromide 30-60 mg orally 2-4 times daily (not oral neostigmine) 2, 1
2. Titrate up to maximum 600 mg daily based on response 2
3. Monitor for side effects (present in 91% of patients) 3

For breakthrough symptoms despite oral pyridostigmine:

1. Consider intranasal neostigmine 1-4 puffs for rapid effect 7, 6
2. Avoid adding oral neostigmine due to drug interaction 4

For MG crisis requiring intubation:

1. Discontinue all oral anticholinesterases 2
2. Use IV neostigmine only if specifically indicated, with appropriate anticholinergic coverage 2, 5