May 16th, 2012

Azithromycin Linked to Cardiovascular Death — Not A Placebo After All

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?

5 Responses to “Azithromycin Linked to Cardiovascular Death — Not A Placebo After All”

  1. Patrick Zimmerman, M.D. says:

    Thank you for your comments, however at present I believe you are fighting a losing battle. Indiscriminate antibiotic prescribing results in happy patients, higher ratings and, in the highly praised health system in which I work, higher income. There might be studies that refute this claim but I see it first hand on a daily basis. Please spread this information to the public and health care leaders to see if we can turn this around.

  2. Howard Heller says:

    “But every time I get sick my doctor gives me a Z-Pak and I ALWAYS get better.”
    It’s hard to deny but I do always explain to my azithromycin addicted patients that azithromycin is an immunomodulator and exerts direct inhibitory effects on mucus secretion and that is the reason why they feel better. For some patients if you can explain to them that the beneficial effect of azithromycin for viral URIs is because of the mucus production they will agree to switch to non-antibiotic mucus decreasing agents.

    I learned of this years ago after a brief chart war with a pulmonologist who was co-consulting on a patient with a tracheostomy copious bronchorrhea. I kept writing to stop the azithromycin because there was no sign of infection and the pulmonologist kept writing to continue the azithromycin. Once we verbally communicated he explained that he agreed that there was no infection but that he was pushing the azithromycin in order to reduce the bronchorrhea.

  3. Cathy says:

    In Polish or English, there’s something brilliant about naming a pharmaceutical company Pilva, stuffed zebras or no stuffed zebras!

  4. Kevin says:

    Dr. Sax you were hilarious during my residency and you still remain hilarious!

  5. Loretta S says:

    I love your musings. And they are important! In this season of coughs, cold and general upper respiratory misery, my patients come in asking for a “Z pack” and aren’t happy when I tell them it’s likely viral and they don’t need a Z pack or any other antibiotic. I have found that the patients who know me and trust me can accept that advice, but the ones who called this morning and asked to “see anyone! I’m desperate!” and who don’t know me are more suspicious of the advice. Giving good symptomatic treatment and telling the patient to call me in 2-3 days if they have seen no improvement will placate most patients. Most. 🙂

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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