What are the reasons to discontinue Pyridostigmine (Mestinon)?

From the Guidelines

Pyridostigmine should be discontinued in patients with severe immune-related adverse events, such as those requiring intubation, or in cases where the medication is no longer effective or is causing significant side effects. The decision to discontinue pyridostigmine is guided by the severity of the patient's condition and the presence of adverse effects. According to the most recent and highest quality study 1, in cases of intubation, pyridostigmine may be discontinued or withheld. Additionally, the study suggests that pyridostigmine starting from 30 mg orally up to 600 mg daily may be used in case of myasthenic symptoms, but its discontinuation is warranted in severe cases.

Reasons for Discontinuation

• Severe immune-related adverse events, such as those requiring intubation
• Ineffective treatment for the patient's condition
• Significant side effects, such as intolerable gastrointestinal symptoms, excessive cholinergic effects, or bradycardia/hypotension that doesn't respond to dose adjustments
• Development of respiratory depression, seizures, or signs of cholinergic crisis
• Achievement of remission or significant improvement after thymectomy in patients with myasthenia gravis
• Significant deterioration of liver or kidney function, leading to potential drug accumulation and toxicity

Management of Discontinuation

When discontinuing pyridostigmine, it is essential to taper the dose gradually rather than stopping abruptly to prevent withdrawal symptoms or worsening of the underlying condition, particularly in myasthenia gravis patients where sudden discontinuation could precipitate a myasthenic crisis, as suggested by previous studies 1. However, the most recent study 1 provides the most up-to-date guidance on the management of immune-related adverse events, including the use and discontinuation of pyridostigmine.

Key Considerations

• Neurological expertise is mandatory in the management of patients with immune-related adverse events
• Corticosteroids and pyridostigmine are the first-line management approach for these patients
• In severe cases, IVIG, plasmapheresis, or other interventions may be necessary
• Frequent pulmonary function assessment and daily neurologic review are crucial in the management of these patients, as indicated by the study 1.

From the FDA Drug Label

Although failure of patients to show clinical improvement may reflect underdosage, it can also be indicative of overdosage. As is true of all cholinergic drugs, overdosage of pyridostigmine bromide may result in cholinergic crisis, a state characterized by increasing muscle weakness which, through involvement of the muscles of respiration, may lead to death The diagnosis of cholinergic crisis, according to Osserman and Genkins1, calls for the prompt withdrawal of all drugs of this type.

The reasons to discontinue Pyridostigmine (Mestinon) are:

• Cholinergic crisis: due to overdosage, which can lead to increasing muscle weakness and potentially death
• Pregnancy or lactation: as the safety of pyridostigmine bromide during pregnancy or lactation in humans has not been established, and its use requires weighing the potential benefits against possible hazards to mother and child 2

From the Research

Reasons to Discontinue Pyridostigmine

• The most frequently cited reasons to discontinue pyridostigmine include diarrhea, abdominal cramps, and muscle twitching, as reported by patients who discontinued the medication 3.
• Side effects were the reason for discontinuation in 26% of patients who stopped using pyridostigmine 3.
• Common side effects of pyridostigmine include flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis, which may lead to discontinuation of the medication 3.
• In some cases, patients may discontinue pyridostigmine due to lack of effectiveness or inadequate symptom control, prompting a switch to alternative treatments such as immunosuppressive therapies 4, 5.

Patient Considerations

• Patients with myasthenia gravis who are taking pyridostigmine should be monitored for potential side effects and adjusted dosages as needed to minimize adverse reactions 3, 6.
• The decision to discontinue pyridostigmine should be made in consultation with a healthcare provider, taking into account the individual patient's response to treatment and potential alternative therapies 4, 5.

Clinical Implications

• Healthcare providers should be aware of the potential side effects and reasons for discontinuation of pyridostigmine in patients with myasthenia gravis, and adjust treatment plans accordingly 3, 7.
• Further research is needed to improve treatment options for myasthenia gravis and to minimize the risk of side effects associated with pyridostigmine and other medications 4, 5.