What is the effect of Neostigmine (an acetylcholinesterase inhibitor) intramuscular (IM) administration in patients with Myasthenia Gravis?

From the Guidelines

Neostigmine can be administered intramuscularly at a dose equivalent to 0.75 mg, as indicated by the conversion from oral pyridostigmine in the management of myasthenic symptoms, particularly in the context of immune-related adverse events 1. The management of myasthenia gravis involves the use of acetylcholinesterase inhibitors like neostigmine and pyridostigmine.

• The dose of neostigmine can be estimated based on its equivalence to oral pyridostigmine, where 30 mg oral pyridostigmine corresponds to 1 mg intravenous pyridostigmine or 0.75 mg neostigmine intramuscularly 1.
• For ongoing management, oral pyridostigmine is generally preferred over IM neostigmine due to better patient tolerance and convenience, with a typical dosing regimen of 30 mg to 600 mg daily 1.
• The mechanism of action involves inhibition of acetylcholinesterase, which increases acetylcholine availability at the neuromuscular junction, temporarily improving muscle strength in myasthenic patients.
• Patients should be monitored for cholinergic side effects including increased secretions, abdominal cramps, diarrhea, and bradycardia.
• It's also important to consider the role of corticosteroids and other immunosuppressive therapies in the management of myasthenia gravis, especially in cases where patients show minimal response to pyridostigmine, as noted in studies from 2020 and 2024 1.
• A comprehensive approach to diagnosis and management, including consultation with a neurologist and the use of diagnostic methods such as acetylcholine receptor antibody testing and electromyography, is crucial for optimal patient outcomes.

From the FDA Drug Label

5.2. Serious Adverse Reactions in Patients with Certain Coexisting Conditions Neostigmine Methylsulfate Injection, USP, should be used with caution in patients with coronary artery disease, cardiac arrhythmias, recent acute coronary syndrome or myasthenia gravis Because of the known pharmacology of neostigmine methylsulfate as an acetylcholinesterase inhibitor, cardiovascular effects such as bradycardia, hypotension or dysrhythmia would be anticipated In patients with certain cardiovascular conditions such as coronary artery disease, cardiac arrhythmias or recent acute coronary syndrome, the risk of blood pressure and heart rate complications may be increased. Risk of these complications may also be increased in patients with myasthenia gravis. Standard antagonism with anticholinergics (e.g., atropine) is generally successful to mitigate the risk of cardiovascular complications.

Neostigmine should be used with caution in patients with myasthenia gravis due to the potential for increased risk of cardiovascular complications such as bradycardia, hypotension, or dysrhythmia.

• The use of anticholinergics (e.g., atropine) is recommended to mitigate this risk. The dose of Neostigmine should be carefully considered to avoid neuromuscular dysfunction and cholinergic crisis. 2

From the Research

Neostigmine IM Administration in Myasthenia Gravis

• Neostigmine is a reversible quaternary cholinesterase inhibitor used to antagonize non-depolarizing neuromuscular blockade in general anesthesia and in the symptomatic treatment of myasthenia gravis 3.
• The oral bioavailability of neostigmine is low, and its plasma concentrations after oral administration are only 1 to 5 micrograms/L 3.
• There is no direct information available on the IM administration of neostigmine in myasthenia gravis in the provided studies.
• However, it is known that neostigmine can be used as an alternative to pyridostigmine in some cases, and its use in myasthenic crisis has been studied 4.
• In myasthenic crisis, continuous intravenous infusion of pyridostigmine or neostigmine can be a substitute for intravenous immunoglobulin or plasmapheresis if these are not available 4.

Pharmacokinetics and Pharmacodynamics

• The plasma clearances of reversible quaternary cholinesterase inhibitors, including neostigmine, are in the range 0.5 to 1.0 L/h/kg, and their apparent volumes of distribution range from 0.5 to 1.7 L/kg 3.
• The elimination half-life of neostigmine is short, in the order of 30 to 90 minutes 3.
• The relationship between plasma concentrations of cholinesterase inhibitors and their pharmacological effects is not entirely clear, especially when evaluating global muscular function in myasthenia gravis 3, 5.

Clinical Use and Monitoring

• Cholinesterase inhibitors, including neostigmine, are still important in the treatment of myasthenic patients, but their use requires careful monitoring due to potential adverse effects and interactions 5, 6.
• Erythrocyte-bound acetylcholinesterase activity can be used as a parameter to monitor the effect of cholinesterase inhibitors, but its usefulness is limited in routine clinical practice 5.
• The treatment of myasthenia gravis is evolving, with new drugs and therapies being developed, including novel acetylcholinesterase inhibitors and immunotherapies 6, 7.