What is the initial treatment for myasthenia gravis?

Initial Treatment for Myasthenia Gravis

Start pyridostigmine (Mestinon) at 30 mg orally three times daily as first-line therapy for all patients with myasthenia gravis, titrating upward based on symptom response to a maximum of 120 mg four times daily. 1, 2, 3

First-Line Symptomatic Treatment

• Pyridostigmine, an acetylcholinesterase inhibitor, is FDA-approved and recommended as the initial treatment for myasthenia gravis across all disease severities. 1, 3
• Begin with 30 mg orally three times daily and gradually increase the dose based on clinical response and tolerability. 1, 2
• The maximum recommended dose is 120 mg orally four times daily. 1, 2
• This symptomatic treatment provides improvement in most patients but is often incomplete and may wane after weeks to months. 4

When to Escalate Beyond Pyridostigmine

For patients with Grade 2 or higher symptoms (moderate weakness affecting daily activities) who have insufficient control with pyridostigmine alone, add corticosteroids directly as second-line therapy. 1, 2

• Initiate prednisone at 1-1.5 mg/kg orally daily. 1, 2
• Corticosteroids demonstrate effectiveness in approximately 66-85% of patients with myasthenia gravis. 2, 5
• Taper corticosteroids gradually based on symptom improvement. 1, 5
• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require corticosteroid escalation. 2, 5

Critical Medications to Avoid

Educate all patients immediately about medications that can precipitate myasthenic crisis, as this is a common and preventable cause of exacerbation. 1, 2

• Avoid β-blockers, intravenous magnesium, fluoroquinolone antibiotics, aminoglycoside antibiotics, and macrolide antibiotics. 1, 2, 5
• Warn specifically about barbiturate-containing medications like Fioricet (butalbital and acetaminophen). 1

Essential Baseline Monitoring

• Confirm diagnosis with acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies. 1, 2
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies. 1, 5
• Perform baseline pulmonary function testing with negative inspiratory force and vital capacity, as respiratory compromise is the primary mortality risk. 1, 2
• Regular pulmonary function assessment is crucial, especially for patients with generalized disease, as 50-80% of patients with initial ocular symptoms may develop generalized myasthenia within a few years. 2

Management of Severe Exacerbations (Grade 3-4)

For myasthenic crisis with respiratory compromise or severe generalized weakness, immediately hospitalize with ICU-level monitoring and initiate IVIG or plasmapheresis. 1

• Administer IVIG at 2 g/kg total dose over 5 days (0.4 g/kg/day for 5 consecutive days). 1
• Plasmapheresis is an equally effective alternative when IVIG is contraindicated or not feasible. 1, 4
• Continue corticosteroids concurrently during acute treatment. 1
• Perform frequent pulmonary function assessments and daily neurologic evaluations. 1
• IVIG should not be used for chronic maintenance therapy—it is reserved exclusively for acute exacerbations requiring hospitalization. 1

Common Pitfall to Avoid

Do not use IVIG for chronic maintenance therapy in myasthenia gravis, as this represents inappropriate use not supported by guidelines. 1 IVIG is indicated only for acute Grade 3-4 exacerbations with respiratory compromise or as an alternative to plasmapheresis in crisis situations. 1

Medication Timing Strategy

• Instruct patients to plan activities around medication timing for optimal strength, as pyridostigmine has a predictable duration of action. 1
• This allows patients to time peak medication effect with periods requiring maximal strength. 1

Follow-Up Requirements

• Schedule regular neurological follow-up to adjust treatment as disease activity changes. 1, 2
• Monitor for worsening symptoms including changes in speech or swallowing (bulbar symptoms), respiratory difficulties, and double vision (diplopia). 1
• Patients must seek immediate medical attention for any significant increase in muscle weakness, as myasthenic crisis requires urgent hospitalization. 1