Azithromycin and cardiovascular risk

Since 2012, the FDA has made two statements regarding the safety of azithromycin related to cardiovascular risk.  These warnings were largely in response to an observational cohort study that found a small absolute increase in cardiovascular deaths in patients receiving azithromycin versus those receiving amoxicillin or no antibiotic in a Tennessee Medicaid population¹.  This excess risk varied based on patients’ baseline cardiovascular risk and was found to be highest in the highest decile of cardiovascular risk.  While a warning from the FDA does seem concerning, it is important to examine some of the details of the data.

• Of the 347,795 azithromycin prescriptions in the study cohort, there were 29 cardiovascular deaths (absolute risk = 0.008%)
• Of the 1,391,180 matched controls, there were 41 cardiovascular deaths (absolute risk = 0.003%)
• These above cardiovascular deaths occurred during the five day treatment course, whereas the analysis that also included the following five days had no difference in death from any cause
• 4,082 prescriptions would have to be used in patients at the highest cardiovascular risk decile to cause one additional cardiovascular death

Serious peripheral neuropathy and fluoroquinolones

This week’s pharmacy pearl describes a recent alert from the FDA that you might have heard about regarding fluoroquinolones.  Fluoroquinolones are a diverse group of antibiotics used to treat various types of infections including pulmonary, genitourinary, skin, gastrointestinal, and bone infections. 

A recent warning from the FDA announced the potential for all systemic (IV or po) fluoroquinolones to cause serious peripheral neuropathy.  While peripheral neuropathy has been a known side effect of fluoroquinolones for nearly a decade, the FDA felt that the nature of this reaction was not sufficiently described.   They state that a large review has shown a continued association between fluoroquinolones and “disabling” peripheral neuropathy.  Peripheral neuropathy may occur rapidly, within a few days, and has persisted for longer than a year, even when the medication was discontinued.  No risk factors were identified, including age and duration of therapy.  The specific incidence or prevalence was not listed and it is likely underreported since the review was done through the FDA’s Adverse Events Reporting System.  Events occurred with all systemic drugs in this class.