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Azithromycin Linked to Cardiovascular Death — Not A Placebo After All

Posted May 16 2012 5:07pm

I’ve commented before about azithromycin, that remarkable antibiotic that clinicians seem to prescribe for, gosh, you-name-it.

But a paper just published in the New England Journal of Medicine links use of azithromycin to an increased risk of cardiovascular death, a reminder that “azithro” is in fact a drug — and that all drugs have side effects.

A few more musings on this extremely popular antibiotic:

  • Has there been anything even close to the universal “penetrance” of the 5-day, 6-pill “Z-Pak” in terms of outpatient antibiotic prescribing? Oddly enough, the first time I wrote for it way back in the early 1990s, the patient I gave it to thought he was being ripped off — not enough pills!
  • Of course, that didn’t last long, many patients now ask for a “Z-Pak” by name. The marketing genius who came up with the “Z-Pak” should win the advertising equivalent of the Nobel Prize, even if he/she would fail a first-grade spelling test.
  • The ubiquitous toy zebras probably didn’t hurt pediatric prescribing either. These trinkets are now forbidden, but  you can pick one up on eBay if you’re feeling nostalgic.
  • Initially, cost-cutters tried to get clinicians to prescribe erythromycin over azithro (and clarithro) since the newer macrolides were so much more expensive. Talk about a losing battle — sometimes newer is not just costly, it’s costly and better. (Ditto fluconazole when it replaced ketoconazole.)
  • Now that azithromycin and clarithromycin are both generic, does anyone regularly use clarithromycin anymore? Yes, it’s more active versus atypical mycobacteria, but hardly enough so to make it worth the increased drug-drug interactions, QT prolongation, excess mortality risk (as seen in prospective studies like  this one ), and peculiar taste disturbance. (It was with clarithromycin that I learned the word  dysgeusia — it means distortion of taste –  and a  famous mycobacterial researcher has a fascinating anecdote about how bizarre champagne tastes when accompanied by a side of Biaxin.)
  • Department of Irony:  Azithromycin was studied as  treatment to prevent cardiac disease. You remember, treat Chlamydia pneumoniae, that notorious “cause” of atherosclerosis, and reduce cardiac events. (It didn’t work.)
  • Little-known fact:  Azithromycin was developed by a then-small  Croatian pharmaceutical company named Pliva in the 1970s, with a world-wide patent in 1981 — 10 years before it was FDA-approved in the USA. At its peak, Pfizer was making more than $1 billion/year on azithromycin sales and, of course, sharing some of that with Pliva (and making stuffed zebras).
  • The downside of all this azithromycin use? Predictably, increased rates of clinically important resistance — especially Strep pneumo and group A strep . Hard to believe that second-line treatment for pneumococcal pneumonia, back when I was in medical school, was erythromycin. Yes, I might be old.

If there’s a silver lining to this report in the NEJM, it’s that clinicians will stop prescribing azithromycin for conditions that clearly don’t need it — which is just about every uncomplicated outpatient respiratory infection.

Hey, we can dream, can’t we?

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