The New England Journal of Medicine (NEJM) published a provocative article this week titled “Azithromycin and the Risk of Cardiovascular Death.” It stimulated dramatic headlines:
“Popular Antibiotic May Raise Risk of Sudden Death.” New York Times, May 16, 2012
“Antibiotic Z-Pak may pose risk of sudden death.” NBC Nightly News, May 17, 2011
“Could a common antibiotic increase risk of cardiac death?” WebMD, May 17, 2012
With such headlines, it is hardly any wonder there are a lot of confused patients and prescribers this weekend. Azithromycin (Z-Pak, Zithromax) is one of the most popular drugs in the pharmacy. At last count, more than 50 million prescriptions for it were dispensed from retail pharmacies last year. It is prescribed for lung infections, sinusitis, earaches, sore throats caused by strep, skin infections and urinary tract infections, to name just a few of the many uses for this broad-spectrum antibiotic.
How could such a useful drug be killing people?
A little-known fact is that the class of antibiotics called macrolides (including clarithromycin and erythromycin as well as azithromycin) can increase the risk for serious irregular heart rhythms and sudden cardiac death. These dangerous arrhythmias have been noted in the medical literature for more than a decade. For reasons that are not entirely clear to us, doctors thought that azithromycin did not share this class effect.
In the NEJM study, researchers analyzed data from more than 500,000 Medicaid patients in Tennessee. Patients who took azithromycin were compared to patients who took amoxicillin (a penicillin-type antibiotic) or ciprofloxacin or levofloxacin (fluoroquinolones) or no antibiotics. Those taking azithromycin were roughly two and a half times more likely to experience sudden cardiovascular death compared to those taking amoxicillin. Interestingly, deaths linked to levofloxacin (Levaquin) were comparable to deaths associated with azithromycin, suggesting that Levaquin might also pose a risk for serious irregular heart rhythms.
The absolute risk was relatively small: about 65 deaths attributed to azithromycin out of one million antibiotic treatments. There were 22 deaths out of a million courses of amoxicillin. The greatest risk was for patients with heart disease. That is to say, people with underlying heart rhythm problems, heart failure, clogged coronary arteries, stents or prior heart attacks were most likely to die while taking azithromycin.
Nevertheless, this study gives a glimpse at another secret that many health professionals prefer to keep under wraps: a surprising number of drugs can cause serious heart rhythm abnormalities. These arrhythmias can lead to stroke or sudden death. These medications are taken by tens of millions of Americans every day!
Let’s start with NSAIDs (non-steroidal anti-inflammatory drugs). You can buy ibuprofen (Advil, Motrin IB, etc) and naproxen (Aleve) over the counter. Then there are the prescription strength NSAIDs that doctors prescribe:
- celecoxib (Celebrex)
- diclofenac (Cataflam, Voltaren)
- etodolac (Lodine)
- ibuprofen (Motrin)
- indomethacin (Indocin)
- ketorolac (Toradol)
- naproxen (Anaprox, Naprosyn)
- meloxicam (Mobic)
- oxaprozin (Daypro)
- piroxicam (Feldene)
- sulindac (Clinoril)
Such drugs can cause atrial fibrillation or flutter (BMJ, online July 4, 2011). People don’t always realize that they have such arrhythmias because symptoms may be subtle or nonexistent. Be on the lookout for lightheadedness, heart palpitations, chest pain or fainting. A potentially serious or even deadly consequence of these irregular heart rhythms is stroke.
The list of other medications that can cause serious heart rhythm irregularities is amazingly long. Here is just a partial list:
- Amiodarone (Cordarone)
- Astemizole (Hismanal)
- Chloroquine (Aralen)
- Chlorpromazine (Thorazine)
- Citalopram (Celexa)
- Dronedarone (Multaq)
- Flecainide (Tambocor)
- Haloperidol (Haldol)
- Moxifloxacin (Avelox)
- Probucol (Lorelco)
- Procainamide (Pronestyl)
- Quinidine (Cardioquin)
- Sotalol (Betapace)
- Thioridazine (Mellaril)
Of course, no one should EVER stop taking any medication without a doctor’s supervision. Some of these drugs are so essential to health that stopping them would pose a far greater risk than any potential arrhythmia. Nevertheless, patients should always be warned about the possibility of drug-induced arrhythmias and told what symptoms to be alert for.
We fear that many physicians may fail to mention possible arrhythmias when they prescribe medications. We consider that a major oversight. To protect yourself and those you love, we suggest reading Top Screwups Doctors Make and How to Avoid Them. It provides questions, tips and checklists to help you prevent unanticipated but deadly drug reactions. You’ll find a list of questions to ask any time you are handed a prescription.