Saturday, March 23, 2013

Should I Worry About Taking Azithromycin?

Azithromycin is one of the most widely used antibiotics in the United States.  In 2011 more than 40 million Americans received a prescription for azithromycin (Zithromax; Z-pak; Zmax).  Recently, the Food and Drug Administration distributed a drug safety announcement regarding the risk of azithromycin in causing fatal heart arrhythmias (irregular heart beat).  Should we now stop using azithromycin?
Here's how this drug safety warning came about.  Last year researchers reviewed the electronic records of Medicaid patients in Tennessee.  They found that persons receiving a short course of azithromycin were more likely to suffer death from cardiovascular disease, especially sudden death thought due to heart arrhythmia, than persons not receiving antibiotics or receiving an alternative antibiotic, amoxicillin.  If you were a person with no special risk for cardiovascular disease, then the increased risk of dying while taking azithromycin was approximately 1 in 111,000.  If you had serious underlying cardiovascular disease or a tendency to develop heart irregularity, the excess risk of dying while taking azithromycin was 1 in 4,000.  To put this in perspective, your risk of dying from a bolt of lightning is estimated at 1 in 84,000, and your risk of dying in an automobile accident is estimated at 1 in 100.
There are two classes of antibiotics that are known to predispose to irregular heart rhythms.  These are the family of antibiotics called macrolides (including azithromycin, clarithromycin [Biaxin], and erythromycin) and fluoroquinolones (including ciprofloxacin [Cipro], levofloxacin [Levaquin], and moxifloxacin [Avelox]).  The study cited above found that the risk of cardiovascular death when taking levofloxacin was the same as when taking azithromycin.  It also found that the risk of death from cardiovascular disease did not persist after the course of antibiotic.

Our take on this evidence? 

1.   The evidence suggesting that azithromycin can stimulate fatal heart arrhythmias is compelling and believable. 

2.      Will we continue to prescribe azithromycin for our otherwise healthy patients and family members for bacterial respiratory tract infections?  Yes.  Antibiotics remain among the relatively few drugs in our medical toolbox that can cure disease.
3.      People who should avoid azithromycin (and other macrolide antibiotics) and levofloxacin (and other fluoroquinolone antibiotics) are those with a known tendency to a particular type of irregular heart rhythm of the ventricle (ventricular arrhythmia) caused by slow electrical repolarization of the heart muscle, manifesting as prolongation of the QT interval on electrocardiogram.  Your doctor will know if you have “prolonged QT syndrome” or are taking other medications that might cause a prolonged QT interval, especially heart medicines such as dofetilide, amiodarone, or sotalol.  A very low blood level of potassium or an abnormally slow heart rate might also put you at risk for this type of heart arrhythmia.

4.      Is this evidence one more reason that otherwise healthy people with viral head and chest colds should take symptomatic treatment (such as acetaminophen [Tylenol], chicken soup, and tea with honey) rather than unnecessary and unhelpful antibiotics?  Definitely yes.

Saturday, March 9, 2013

Asthma and Your Bone Health

Asthma is a disease of the lungs, not the bones. There are no bones in our bronchial tubes, right? So where is the connection?

The most important connection relates to the anti-inflammatory steroids ("corticosteroids") used to treat asthma. Prednisone and methylprednisolone (Medrol), if taken regularly or for many months of the year, can have major effects on the bones. In children they can impair bone growth, leading to lesser height as an adult. In adults steroids can decrease bone mass and predispose to the thinning of the bones called osteoporosis. Osteoporosis is a condition without symptoms but one that predisposes to fractures, sometimes with minimal or no trauma. Osteoporosis can cause vertebrae to collapse in on themselves (vertebral compression fractures), ribs to break with coughing or twisting, and hips to break when we fall.

Because of these and many other negative effects of corticosteroids taken as tablets (and distributed via the bloodstream to all parts of the body), safer alternatives to treat the inflamed airways of asthma were developed. In the 1960s corticosteroids that could be delivered directly to the bronchial tubes in the form of medication aerosols became available. The first widely used formulation was beclomethasone by metered-dose inhaler. Since then other corticosteroid preparations have become available, some as metered-dose inhalers, some as dry-powder inhalers, and one as a solution for nebulization. These medications are given in a small fraction of the dose of oral steroid tablets, and only a small portion of the inhaled medication makes its way into the bloodstream, to be carried to the bones and elsewhere throughout the body. As a result inhaled steroids are far safer for the bones than oral steroids.

And yet. A small portion of the inhaled steroid can be absorbed into the blood and carried to the bones. If the dose of inhaled steroid is high enough and the duration of use long enough, it is possible that over a period of several years steroids by inhalation, like steroids swallowed as tablets, can have some effect on bone health. And for many people, it is not an either-or proposition. Many people require daily inhaled steroids for control of asthma plus occasional bursts of oral steroids to reverse flare-ups or asthma attacks.

The potential risk to your bones from long-term use of high doses of inhaled steroids does not mean that you should stop using your steroid inhaler. In most instances, inhaled steroids prevent or reduce the need for oral steroid tablets, which have a far greater impact on your bones. Rather, it means that we -- patients and healthcare providers alike -- need to be vigilant about maintaining good bone health. Regular weight-bearing physical activity is a good place to start to strengthen our bones. Adequate intake of calcium and vitamin D, either in our diets or as dietary supplements, is important "fuel" for our bones. Also, several prescription medicines are available that can slow the development of osteoporosis and even reverse it.

Your healthcare provider can help you assess your risk for low bone mass. He or she may recommend measurement of your bone density with an X-ray specifically designed for this purpose, called bone densitometry or a "DEXA" scan (dual-energy X-ray absorptiometry scan). Persons at risk for osteoporosis (especially -- but not only -- thin women following menopause) are typically screened with bone density X-rays approximately every two years. Remember: good breathing and good bone health are both achievable.