How to safely discontinue pyridostigmine (Mestinon) 60 mg three times a day (tid)?

How to Safely Discontinue Pyridostigmine 60 mg TID

Pyridostigmine should be gradually tapered rather than abruptly discontinued to prevent rebound worsening of symptoms, especially in patients with myasthenia gravis or orthostatic hypotension. 1

General Tapering Approach

• Begin by reducing the dose by 30 mg (half a tablet) every 3-7 days while monitoring for symptom recurrence 1
• Maintain at least 6 hours between doses during the tapering process 2
• If symptoms worsen during tapering, return to the previous well-tolerated dose and slow the tapering schedule 1
• Consider neurological consultation before initiating the taper, especially for patients with myasthenia gravis 1

Specific Tapering Schedule

For Myasthenia Gravis Patients:

1. Week 1: Reduce to 60 mg twice daily (morning and evening) 1, 2
2. Week 2: Reduce to 60 mg in morning and 30 mg in evening 1
3. Week 3: Reduce to 30 mg twice daily 1
4. Week 4: Reduce to 30 mg once daily 1
5. Week 5: Discontinue completely 1

For Orthostatic Hypotension Patients:

• The tapering can generally be more rapid, over 1-2 weeks 1, 3
• Monitor blood pressure in both supine and standing positions during the taper 1

Monitoring During Discontinuation

• Watch for signs of symptom recurrence, which may indicate the need to slow the tapering process 1
• For myasthenia gravis patients: monitor for increased muscle weakness, fatigue, ptosis, diplopia, or difficulty swallowing 1, 4
• For orthostatic hypotension patients: monitor for dizziness, lightheadedness, or significant drops in blood pressure upon standing 1, 3

Special Considerations

• Patients with more severe underlying conditions may require slower tapering schedules 1
• If the patient is also on corticosteroids for myasthenia gravis, do not taper both medications simultaneously 1
• Avoid medications that can worsen myasthenia symptoms during the tapering process (β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides) 1
• Be aware that prolonged pyridostigmine use may cause neuromuscular dysfunction that can persist even after discontinuation 5

When to Seek Immediate Medical Attention

• Development of significant weakness, especially involving respiratory muscles 1
• Difficulty swallowing or breathing 1
• Severe orthostatic symptoms with significant drops in blood pressure 1

Common Withdrawal Effects

• Temporary increase in muscle weakness in myasthenia gravis patients 4
• Increased orthostatic symptoms in patients treated for orthostatic hypotension 1, 3
• Potential gastrointestinal symptoms as side effects resolve (diarrhea, abdominal cramps may temporarily worsen before improving) 4

Remember that individual responses to pyridostigmine discontinuation vary significantly, and the tapering schedule may need adjustment based on the patient's specific response 4, 6.