What is the recommended treatment and dosage for myasthenia gravis using Pyridoostigmine (Mestinon)?

Pyridostigmine Treatment for Myasthenia Gravis

The recommended initial treatment for myasthenia gravis is pyridostigmine at a starting dose of 30 mg orally three times daily, which can be gradually increased to a maximum of 120 mg orally four times daily (up to 600 mg daily) as tolerated based on symptoms. 1

Dosing Guidelines

Initial Dosing

• Start with 30 mg orally three times daily 1
• For the oral solution: average dose is 10 teaspoons (60 mg/teaspoon) daily, spaced to provide maximum relief when maximum strength is needed 2

Dose Titration

• Gradually increase based on symptom control and tolerability
• Maximum recommended dose: 120 mg orally four times daily 1
• Maximum daily dose can be up to 600 mg for severe symptoms 1
• In mild cases, 1-6 teaspoons (60-360 mg) daily may be sufficient 2
• In severe cases, up to 25 teaspoons (1500 mg) daily may be required 2

Medication Formulations

• Available as tablets and oral solution
• Solution (60 mg/5 mL) is particularly useful for:
  • Children requiring fraction of adult doses
  • "Brittle" myasthenic patients needing precise dosage adjustments
  • Patients with bulbar involvement who have difficulty swallowing, especially in the morning 2
• Sustained-release formulation (where available) can reduce dosing frequency from 4.3 to 3.6 times daily and improve quality of life 3

Treatment Escalation

For patients with inadequate response to pyridostigmine alone:

1. Add corticosteroids (prednisone 0.5-1.5 mg/kg orally daily)
   • 66-85% of patients show positive response 1
2. Consider steroid-sparing agents concurrently:
   • Methotrexate: 15 mg weekly
   • Azathioprine: 2 mg/kg of ideal body weight in divided doses
   • Mycophenolate mofetil: 500 mg twice daily increasing to 1000 mg twice daily 1

Monitoring Treatment Response

• Regular neurological assessments
• Pulmonary function tests including negative inspiratory force (NIF) and vital capacity (VC)
• Close monitoring for patients with NIF -20 to -60 cm H₂O 1
• In some cases, monitoring erythrocyte-bound acetylcholinesterase activity may be useful to assess drug effectiveness 4

Side Effects Management

Be aware that 91% of patients report side effects 5:

• Most common: flatulence, urinary urgency, muscle cramps, blurred vision, hyperhidrosis
• Reasons for discontinuation: diarrhea, abdominal cramps, muscle twitching

Important Considerations

• Individualize dosing based on clinical response rather than plasma concentrations 4
• For surgical patients, continuing pyridostigmine until the day of surgery is recommended to prevent respiratory discomfort, though this may affect response to neuromuscular blocking agents 6
• Avoid medications that can worsen myasthenia, including β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 1

Perioperative Considerations

• For patients undergoing surgery:
  • Continue pyridostigmine through the day of surgery to prevent respiratory compromise 6
  • Be aware that pyridostigmine continuation may alter response to neuromuscular blocking agents
  • Rocuronium is preferred as it can be antagonized with sugammadex 1
  • Avoid atracurium, mivacurium, and succinylcholine 1

The dosage and administration should be carefully adjusted based on individual patient response, with close monitoring for both therapeutic effects and potential side effects.