From the Guidelines
Pyridostigmine should be discontinued in patients with myasthenia gravis who experience severe side effects, achieve remission, or undergo thymectomy with significant improvement, as well as in cases of cholinergic crisis or when the medication is no longer effective. The decision to discontinue pyridostigmine should be made by a healthcare provider, taking into account the patient's individual condition and the potential for worsening of symptoms. In patients treated with immune checkpoint inhibitor therapy, pyridostigmine may be discontinued or withheld in case of intubation, as stated in the management of IR-neuro(muscular) toxicity guidelines 1. Common reasons for discontinuation include gastrointestinal distress, excessive sweating, increased bronchial secretions, or bradycardia. For patients experiencing severe symptoms, such as those with grade 3-4 immune-related adverse events, permanent discontinuation of immune checkpoint inhibitors and initiation of corticosteroids, IVIG, or plasmapheresis may be necessary, as recommended in the ASCO guideline update 1. Gradual tapering rather than abrupt discontinuation is recommended to prevent rebound symptoms, especially in long-term users. Pyridostigmine works by inhibiting acetylcholinesterase, increasing acetylcholine availability at neuromuscular junctions, so discontinuation requires careful management to prevent symptom exacerbation. Key considerations for discontinuation include:
- Severe side effects or allergic reactions
- Achievement of remission or significant improvement after thymectomy
- Cholinergic crisis
- Lack of effectiveness
- Intubation in patients with immune-related adverse events
- Grade 3-4 immune-related adverse events requiring permanent discontinuation of immune checkpoint inhibitors and initiation of alternative treatments. It is essential to prioritize the patient's safety and well-being when making decisions about pyridostigmine discontinuation, and healthcare providers should carefully weigh the potential benefits and risks of discontinuation in each individual case, as supported by the highest quality and most recent evidence 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: a state characterized by increasing muscle weakness which can lead to death
- Overdosage: which can result in cholinergic crisis
- Pregnancy or lactation: due to the unknown safety of pyridostigmine bromide in humans during these conditions 2
From the Research
Reasons to Discontinue Pyridostigmine
- Side effects were the reason for discontinuation in 26% of patients who stopped using pyridostigmine, as reported in a study published in 2022 3.
- The most frequently cited reasons to discontinue pyridostigmine were:
- Diarrhea
- Abdominal cramps
- Muscle twitching, as found in the same study 3.
- Other side effects associated with pyridostigmine use include:
- Flatulence
- Urinary urgency
- Muscle cramps
- Blurred vision
- Hyperhidrosis, also reported in the 2022 study 3.
- In a case series of patients with systemic sclerosis, 15 out of 31 patients reported adverse effects from pyridostigmine, with diarrhea being the most common side effect 4.
- Although pyridostigmine is generally considered safe and effective for the treatment of myasthenia gravis, some patients may need to discontinue its use due to side effects or inadequate response to treatment, as discussed in a review of MG treatment published in 2011 5.