Can azithromycin (macrolide antibiotic) cause seizures in patients with a history of seizure disorders?

Azithromycin and Seizure Risk in Patients with Seizure Disorders

Azithromycin should be used with caution in patients with seizure disorders as seizure events have been reported during postmarketing use, though no epidemiologic studies have demonstrated an increased seizure risk specifically with azithromycin. 1

Evidence on Azithromycin and Seizures

• Seizure events have been reported during postmarketing surveillance of azithromycin, though the causal relationship has not been firmly established through epidemiologic studies 1
• Azithromycin's adverse effects profile includes neurologic manifestations such as dizziness, headache, vertigo, somnolence, and in rare cases, more serious neuropsychiatric effects including seizures 1
• Case reports have documented severe neuropsychiatric manifestations associated with azithromycin, including partial complex seizures in pediatric patients, suggesting a potential risk in susceptible individuals 2

Comparison with Other Antibiotics

• Unlike some beta-lactam antibiotics (particularly cephalosporins) which have well-documented pro-convulsive activity, macrolides like azithromycin have a relatively lower seizure risk profile 3, 4
• Antibiotics with the highest seizure-inducing potential include penicillins, cephalosporins, fluoroquinolones, and carbapenems, while macrolides are generally considered to have lower pro-convulsive activity 4

Risk Factors for Drug-Induced Seizures

• Patients with pre-existing seizure disorders are at higher risk for drug-induced seizures with many medications 5
• Other risk factors that may increase the likelihood of azithromycin-induced seizures include:
  • Blood-brain barrier dysfunction 4, 5
  • Renal failure (though less significant for azithromycin than for beta-lactams) 4
  • Polypharmacy, especially with other medications that lower seizure threshold 5
  • Extremes of age (very young or elderly patients) 5

Management Recommendations

• For patients with seizure disorders requiring macrolide antibiotics, consider monitoring more closely during treatment initiation 1
• If neurological symptoms develop during azithromycin therapy, consider discontinuation and evaluation for alternative antibiotics with even lower seizure risk 4
• Ensure anticonvulsant medications are optimized before initiating azithromycin in patients with a history of seizures 5
• Avoid concomitant use of other medications known to lower seizure threshold when possible 5

Important Caveats

• The risk of seizures with azithromycin appears to be lower than with many other antibiotics, particularly beta-lactams 4
• Seizure events associated with azithromycin typically occur within 24 hours after the initial dose, as reported in case studies 2
• The decision to use azithromycin in patients with seizure disorders should balance the risk of seizures against the need for appropriate antimicrobial therapy for the specific infection 5
• If azithromycin is the most appropriate antibiotic choice based on the infection being treated, the benefit may outweigh the relatively low seizure risk in most patients with well-controlled seizure disorders 4, 5