What are the side effects of Pyridostigmine (Mestinon)?

Pyridostigmine Side Effects

Pyridostigmine (Mestinon) commonly causes muscarinic and nicotinic side effects, with gastrointestinal symptoms being the most prevalent adverse reactions. 1

Common Side Effects

Muscarinic Side Effects

• Gastrointestinal symptoms:
  • Nausea and vomiting
  • Diarrhea and abdominal cramps
  • Increased peristalsis
  • Flatulence 2
• Increased secretions:
  • Excessive salivation
  • Increased bronchial secretions
  • Hyperhidrosis (excessive sweating)
• Urinary symptoms:
  • Urinary urgency
  • Urinary incontinence 3, 1
• Visual changes:
  • Miosis (pupil constriction)
  • Blurred vision 2

Nicotinic Side Effects

• Neuromuscular symptoms:
  • Muscle cramps and fasciculations
  • Muscle weakness
  • Muscle twitching 1, 2

Frequency and Severity

The prevalence of side effects is remarkably high, with studies showing that up to 91% of patients using pyridostigmine report at least one side effect 2. The most commonly reported side effects in clinical practice include:

1. Flatulence
2. Urinary urgency
3. Muscle cramps
4. Blurred vision
5. Hyperhidrosis 2

Serious Adverse Effects

Cholinergic Crisis

Overdosage of pyridostigmine can result in cholinergic crisis, characterized by:

• Progressive muscle weakness
• Respiratory muscle involvement that may lead to respiratory failure
• Potentially fatal if not recognized and treated promptly 1

This is particularly important to distinguish from myasthenic crisis (worsening of the underlying condition), as the treatments are opposite - cholinergic crisis requires withdrawal of pyridostigmine while myasthenic crisis requires increased dosage 1.

Management of Side Effects

1. Dose adjustment: Many side effects are dose-related and can be managed by careful dose titration 4

2. Atropine administration: Muscarinic side effects can be counteracted with atropine, though this should be used cautiously 1

3. Timing of medication: Taking pyridostigmine with food may reduce gastrointestinal side effects 3

4. Discontinuation: In cases of severe side effects or cholinergic crisis, prompt withdrawal of the medication is necessary 1

Special Populations

• Pregnancy: Safety during pregnancy has not been established; use requires weighing potential benefits against possible risks to mother and child 1

• Elderly patients: May be more susceptible to side effects and should start with lower doses 5

• Patients with autonomic dysfunction: May experience more pronounced cardiovascular effects 5

Clinical Pearls

• Diarrhea, abdominal cramps, and muscle twitching are the most frequently cited reasons for discontinuation of pyridostigmine 2

• Despite side effects, many patients (58-81%) who experience clinical benefit choose to continue therapy 6

• The clinical recovery from pyridostigmine overdose is typically faster than the spontaneous recovery of cholinesterase enzyme activity 7

• In patients with neurogenic orthostatic hypotension, pyridostigmine may improve orthostatic tolerance through increases in peripheral vascular resistance and blood pressure 3

• For myasthenic symptoms, pyridostigmine can be started at 30 mg orally and titrated up to 600 mg daily as needed 3

Monitoring Recommendations

• Regular assessment of symptom improvement versus side effect burden
• Vigilance for signs of cholinergic crisis (increasing weakness, respiratory difficulties)
• In patients with orthostatic hypotension, monitor blood pressure in both supine and standing positions 5

Understanding these side effects and their management is crucial for optimizing treatment outcomes and ensuring patient safety when prescribing pyridostigmine.