What are the symptoms of overtreatment with pyridostigmine (Mestinon) in an elderly male and when to reduce the dose?

From the Guidelines

Pyridostigmine dosage should be reduced in an elderly man when cholinergic overactivity symptoms appear, including excessive salivation, sweating, abdominal cramping, diarrhea, nausea, vomiting, increased bronchial secretions, bradycardia, and muscle weakness or fasciculations. These symptoms occur because pyridostigmine inhibits acetylcholinesterase, leading to acetylcholine accumulation at cholinergic synapses. When these symptoms develop, immediately reduce the dose by 25-50% and contact the prescribing physician, as recommended by the most recent guidelines 1. The medication should be taken with food to minimize gastrointestinal side effects, and doses should be spaced evenly throughout the day. Elderly patients are particularly susceptible to overtreatment due to age-related changes in drug metabolism and elimination, as well as increased blood-brain barrier permeability. Regular monitoring is essential, especially after dose adjustments, and neurology consultation is strongly recommended 2, 1. If severe symptoms develop, such as respiratory difficulty or significant bradycardia, emergency medical attention should be sought immediately, as atropine may be needed to counteract cholinergic excess. Some key points to consider when managing pyridostigmine dosage in elderly patients include:

• Starting with a low dose, such as 30 mg PO three times a day, and gradually increasing to a maximum of 120 mg PO four times a day as tolerated and based on symptoms 2
• Weaning corticosteroids based on symptom improvement, with a typical dose of prednisone 0.5 mg/kg orally daily 1
• Considering inpatient care for patients with grade 2 or higher symptoms, as they can deteriorate quickly 1

From the FDA Drug Label

WARNINGS 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 ADVERSE REACTIONS The side effects of pyridostigmine bromide are most commonly related to overdosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness.

The symptoms of overtreatment with pyridostigmine in an elderly man may include:

• Muscarinic side effects: nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis, and diaphoresis
• Nicotinic side effects: muscle cramps, fasciculation, and weakness
• Cholinergic crisis: increasing muscle weakness, which can lead to death

To manage overtreatment, the dose of pyridostigmine should be cut if the patient exhibits signs of cholinergic crisis or muscarinic and nicotinic side effects. The treatment of cholinergic crisis involves the prompt withdrawal of all drugs of this type and the immediate use of atropine 3.

From the Research

Symptoms of Overtreatment with Pyridostigmine

• Muscle cramps 4
• Diarrhea 4, 5
• Abdominal cramps 4
• Muscle twitching 4
• Flatulence 4
• Urinary urgency 4
• Blurred vision 4
• Hyperhidrosis 4
• Cardiac arrhythmia 5
• Pneumonia 5

When to Cut the Dose

• If side effects are severe or unbearable 4, 6
• If the patient experiences a significant decrease in functional motor status 7
• If the patient develops complications such as cardiac arrhythmia or pneumonia 5
• In cases of severely impaired renal function, as it may prolong the elimination of pyridostigmine 8

Considerations for Dose Adjustment

• Plasma concentrations of pyridostigmine and their correlation with pharmacological effects should be considered 8
• The oral bioavailability of pyridostigmine is approximately 10%, which may affect dosing 8
• Intraindividual variations in plasma concentration during a dose interval are small in myasthenic patients receiving oral maintenance therapy 8
• The effectiveness and net benefit of pyridostigmine should be assessed regularly to guide dose adjustments 4