Azithromycin — is it mother's milk for blepharitis?
Note this post discusses an off-label use of azithromycin.
Inspire Pharmaceuticals' AzaSite has changed the way I think about blepharitis.
For years, like every other ophthalmologist, I've taken great effort to instruct patients with blepharitis about the benefits of eyelid hygiene and warm compresses and how to use them. I've also prescribed erythromycin ointment for use at night. Patients seem to do well for a short while, then symptoms slowly return, prompting a visit back to the office. After reviewing their treatment plan, I've most frequently found these folks are compliant with taking the erythromycin but have slowly phased out the use of warm compresses the most effective part of the regimen. It has became fairly clear that busy people have the discipline to put in a medication, but even with repeated instruction, they fall off the wagon of using time-consuming eyelid hygiene and warm compresses.
Then a colleague suggested I try topical azithromycin instead of erythromycin for these patients.
My first reaction to this was that azithromycin was an unnecessarily expensive and high-tech solution to a very low-tech problem. If warm compresses could treat blepharitis, patients darn well ought to use them. But the reality seemed to be that most of my patients would only make the effort to use warm compresses if and when they became highly symptomatic, by which time the vicious cycle of meibomian inspissation-bacterial colonization-more inspissation had spiraled out of control.
These patients need maintenance therapy they can live with that will keep their blepharitis controlled. So why would I consider azithromycin instead of the freely available and less expensive erythromycin?
Azithromycin well-known to primary care physicians as the cure-all Z-pack has been made available in eye drop form by Inspire for about 2 years under the trade name AzaSite. Although it's official indication is for bacterial conjunctivitis, more and more ophthalmologists have used it off-label for chronic therapy of posterior blepharitis (meibomian gland dysfunction).
Like doxycycline, an antibiotic that is used in blepharitis to thin meibomian secretions rather than for its antimicrobial properties, azithromycin has effects on local tissues (conjunctiva) that go beyond the usual effect of an antibiotic. Azithromycin seems to have anti-inflammatory effects because of actions of its effects on matrix metalloproteinases. Within about a day of use, patients seem to notice less inflammation.
Naturally, azithromycin's antibiotic properties are important to its functioning as a blepharitis treatment. In fact, this is where the drug really seems to excel. Azithromycin has not only high potency against the gram-positive organisms responsible for meibomian gland dysfunction, it also has conjunctival tissue penetration that is off-the-charts compared with other topicals. That suggests it may reside in tissues for a much longer time, allowing effective therapy with very infrequent dosing.
In treating blepharitis (again off-label), I instruct patients to use the drop once a day for a week, then stop for 3 weeks, then start again for a week and repeat the cycle. Many patients mark their calendars to remind them to take drops for 1 week each month.
The major complaint patients seem to have with AzaSite is stinging. It can be uncomfortable to use initially. Some of my patients tell me that refrigerating the drop considerably reduces these symptoms.
Another concern is that the drop is so viscous that it can be difficult to dispense; when the bottle is inverted, the patient has to shake down the contents or just wait for the liquid to roll down to the tip. (Remember the Heinz ketchup "Anticipation" commercials?) Some of our patients have worked around this by storing the bottle upside down, just as we do with gonioscopy gel.
I hope never to give up the crusade for warm compresses and eyelid hygiene, which are the real "mother's milk" we can offer people with blepharitis, but until human nature allows our patients to continue these time-consuming treatments faithfully, we will continue to need other treatments, such as azithromycin, that come out of a box.
Dr. Hovanesian is a consultant to Allergan, Bausch & Lomb, Inspire, Ista Pharmaceuticals, Sirion Therapeutics and Vistakon.