What medications should be avoided in patients with myasthenia gravis?

Medications to Avoid in Myasthenia Gravis

Patients with myasthenia gravis must strictly avoid beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics, as these medications can precipitate myasthenic crisis and respiratory failure. 1

High-Risk Medications That Worsen Neuromuscular Transmission

Antibiotics

• Aminoglycosides (gentamicin, tobramycin, amikacin, neomycin, streptomycin) directly block neuromuscular transmission and are contraindicated in myasthenia gravis 1, 2, 3
• Neuromuscular blockade, respiratory failure, and prolonged respiratory paralysis occur more commonly and severely in patients with myasthenia gravis receiving aminoglycosides 2
• Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) worsen neuromuscular blockade and should be avoided 4, 1
• Macrolide antibiotics (azithromycin, erythromycin, clarithromycin) can precipitate myasthenic crisis 1, 5
• Even amoxicillin, traditionally considered safe, has been associated with acute MG exacerbations in case series, requiring close monitoring if used 6

Cardiovascular Medications

• Beta-blockers worsen neuromuscular weakness and can precipitate crisis 1, 5
• IV labetalol specifically has been associated with myasthenic exacerbations in recent studies 5
• Alpha-blocking drugs show signals for increased risk of myasthenia worsening in pharmacovigilance data 7
• Safer alternatives include angiotensin receptor antagonists, ACE inhibitors, and diuretics for hypertension management 7

Electrolyte Replacement

• IV magnesium impairs neuromuscular transmission and is absolutely contraindicated 1, 8, 5
• Magnesium should not be repleted even in myasthenic crisis, as it can worsen neuromuscular weakness and precipitate respiratory failure 8
• If severe hypomagnesemia requires treatment, consult neurology before any administration 8

Muscle Relaxants and Psychiatric Medications

• Barbiturates (butalbital-containing medications like Fioricet) pose particular risk for respiratory compromise 9
• Methocarbamol is contraindicated as it interferes with pyridostigmine bromide effects 9
• Orphenadrine is contraindicated due to anticholinergic properties that antagonize acetylcholinesterase inhibitors 9
• Tizanidine shows signals for increased risk in pharmacovigilance databases 7

Anesthetic Considerations

Contraindicated Agents

• Depolarizing agents (suxamethonium/succinylcholine) are absolutely contraindicated due to risk of prolonged effect 1, 2
• Atracurium and mivacurium should be avoided; rocuronium and vecuronium are safer alternatives 4

Dose Adjustments Required

• Non-depolarizing muscle relaxants require 50-75% dose reduction in myasthenia gravis patients 1
• Sugammadex is recommended for reversal of steroidal muscle relaxants when necessary 1
• Neostigmine for reversal should be used with caution as it may interfere with long-term MG treatment 1

Safer Anesthetic Options

• Propofol for induction 4
• Sevoflurane or isoflurane for inhalational anesthesia 4
• Fentanyl or remifentanil for analgesia 4
• Lidocaine or bupivacaine for local anesthesia 4

Immune Checkpoint Inhibitors

For patients receiving cancer immunotherapy, immune checkpoint inhibitors can trigger or exacerbate myasthenia gravis and require specific management protocols. 4, 1

• Grade 2 symptoms: Hold immune checkpoint inhibitors 1
• Grade 3-4 symptoms: Permanently discontinue immune checkpoint inhibitors 1
• Initiate methylprednisolone 2 mg/kg IV for severe symptoms 4
• Consider plasmapheresis or IVIG if no improvement or worsening occurs 4

Clinical Context and Risk Factors

Symptomatic patients with generalized myasthenia gravis are especially vulnerable to drug-induced exacerbations, while stable patients with minimal symptoms are at lower risk. 10

Additional Risk Factors for Exacerbation

• Recent studies show that 5 out of 7 medication-induced exacerbations occurred in patients with at least one other risk factor present 5
• Respiratory infection (bacterial or viral) is the most frequent trigger factor for myasthenic crisis 11
• Fever, physical exhaustion, and emotional stress increase vulnerability 11

Safer Antibiotic Alternatives

When antibiotics are necessary:

• Topical bacitracin is safe for ophthalmic use 1
• Penicillins are generally considered safer, though close monitoring is warranted given case reports of amoxicillin-associated exacerbations 6
• Consult neurology for antibiotic selection when treatment is required 1

Monitoring Protocol

When potentially problematic medications must be used:

• Monitor for worsening muscle weakness, particularly proximal limb and ocular muscles 4
• Assess respiratory function with vital capacity and negative inspiratory force 9
• Watch for bulbar symptoms (speech, swallowing difficulties) 4, 9
• Monitor for diplopia and ptosis 4
• Most exacerbations occur within days of medication administration 6
• Full recovery typically occurs within 1-2 months after discontinuation 6