The evidence is not definitive, but an advisory committee could not rule out a causal relationship.
A warning on rare but sudden cardiovascular death has been added to the product information on azithromycin, which already carried a warning of ventricular arrhythmias associated with prolonged QT interval.
The TGA advises clinicians to consider precautionary ECG screening for patients with a high risk of a prolonged QT.
Azithromycin, sold as Zithromax, is the first-line treatment for Mycoplasma pneumoniae infections, which are surging this winter.
Azithromycin powder is among products listed by the TGA as being in critical shortage, thanks to “unexpected increase in consumer demand”, with supply estimated to return in late November.
The product information now says under “Special warnings and precautions for use”:
“Some observational studies have shown an approximately two-fold increased short-term potential rare risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin. The data in these observational studies are insufficient to establish or exclude a causal relationship between acute cardiovascular death and azithromycin use.
“This potential risk was noted to be greater during the first 5 days of azithromycin use. In patients whose medical history and/or ongoing medical treatments place them at high risk for a prolonged QTc, consider performing a screening ECG.”
Under adverse effects it says:
“Cardiovascular disorders: hypotension; palpitations and arrhythmias including ventricular tachycardia have been reported. There have been rare reports of QT prolongation, torsades de pointes and cardiovascular death.”
The decision to add the warning follows a similar US move in 2021. The TGA said it had received four case reports in adults aged between 26 and 84 “possibly associating azithromycin with cardiovascular death”. In two of the deaths, azithromycin was the only suspect medication.
An observational study of nearly eight million antibiotic exposures published in JAMA Network Open in 2020 found roughly double the risk of cardiovascular death associated with azithromycin exposure compared with amoxicillin within five days of exposure.
A summary from the Advisory Committee on Medicines, which discussed the evidence on azithromycin in its last meeting of 2023, said: “Overall, the ACM noted that the case reports provided limited evidence to support this signal and the literature review was inconclusive for this signal due to inconsistent evidence. On balance, the ACM was of the view that the signal is very difficult to interpret, however, at this time, based on the available data, the ACM was unable to definitively state that there is not a signal of harm.
“The ACM advised that while the evidence is currently inconsistent, an additional statement regarding the risk of cardiovascular death and requisite precautionary monitoring should be considered for inclusion within the Australian PI. The ACM noted that this proposed addition to the PI should alert but not alarm clinicians and patients.”
