Life‐Threatening Bradyarrhythmia After Massive Azithromycin Overdose

Abstract

9-month-old infant was inadvertently administered azithromycin 50 mg/kg, taken from floor stock, instead of the prescribed ceftriaxone. Shortly thereafter, she became unresponsive and pulseless. The initial heart rhythm observed when cardiopulmonary resuscitation was started was a widecomplex bradycardia, with a prolonged rate-corrected QT interval and complete heart block. The baby was resuscitated with epinephrine and atropine, but she suffered severe anoxic encephalopathy. Torsade de pointes and QT-interval prolongation have been reported after administration of macrolide antibiotics, including azithromycin, both intravenously and orally. This has occurred especially in the context of coadministered drugs that inhibit the cytochrome P450 (CYP) 3A4 isoenzyme, such as ketoconazole and astemizole. However, bradycardia with complete heart block has not, to our knowledge, been reported specifically with intravenous administration of azithromycin alone, either with therapeutic doses or overdose. Clinicians should be alerted about the potential of azithromycin to cause life-threatening bradycardia, and pharmacy systems should be implemented to ensure special care in the safe administration of this drug, especially when dispensed from a point-of-care source.

Azithromycin Causes a Novel Proarrhythmic Syndrome

“…Second, acute intravenous exposure 14 (in one case causing overdose 15 ) can cause wide-spread depression of cardiac conduction, resulting in marked sinus bradycardia, slowing of AV nodal and infranodal conduction with heart block, and prolonged ventricular repolarization. For conscious mice and cardiomyocytes, we found that acute exposure to azithromycin had similar effects, with in vitro evidence of multi-ion channel block, providing a mechanistic basis for the electrophysiologic effects of acute toxicity.…”

“…12, 13 This likely accounts for increased mortality in patients with coronary artery disease treated with Na + channel blockers, and in the Brugada syndrome, where Na + current is down-regulated. In the setting of overdose and IV administration, 14, 15 azithromycin can cause QRS widening suggesting I Na block, but this has not been reported during oral dosing. Second, excessive prolongation of ventricular repolarization promotes abnormal triggered activity in the form of early afterdepolarizations (EADs) and ultimately torsades de pointes.…”

Azithromycin To Prevent Bronchopulmonary Dysplasia in Ureaplasma-Infected Preterm Infants: Pharmacokinetics, Safety, Microbial Response, and Clinical Outcomes with a 20-Milligram-per-Kilogram Single Intravenous Dose

“…There is a single case report in the literature of cardiac arrest with suspected prolonged QT in a 9 month old who inadvertently received 50 mg/kg azithromycin intravenously over 20 min (31). Prolonged QT interval is rare among newborns with an incidence of the heritable long QT syndromes estimated between 1 per 3,000 and 1 per 5,000 births (32).…”

Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease

“…Nevertheless, we are not aware of doses higher than 4 g being administered or of doses of 4 g being administered daily. Although reports of azithromycin overdose are thankfully rare, based on a PubMed search, in one case an infant inadvertently received 10 mg of azithromycin/kg and developed lifethreatening bradyarrhythmias (36). Thus, caution is needed, and the safety of higher doses would have to be established in the clinic before we can recommend their use.…”