Off-label use of oral antibiotics effective for a variety of conditions

J. James Thimons

The off-label use of oral antibiotics can be very helpful in treating recalcitrant infections of the eyelid, corneal erosions and corneal ulcers. However, when using the cycline class of antibiotics, a practitioner must be judicious in the treatment dosage and duration prescribed.

“I think the cavalier use of any antibiotics, cyclines or otherwise, is not a good idea,” said J. James Thimons, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at Ophthalmic Consultants of Connecticut in Fairfield. “Practitioners need to be aware that if a patient does have a significant lid dysfunction, other alternatives should be looked at first. But if they are unsuccessful, I think doxycyline should be put into play.”

Mechanisms of action

When using an antibiotic for conditions such as meibomian gland dysfunction, recurrent corneal erosions and corneal ulcers, the mechanism of action is predominantly inflammatory, practitioners say.

“The concept is that you are using the drug to treat the dysfunction of the posterior lid vs. using the drug as an anti-infective,” Dr. Thimons told Primary Care Optometry News. “The drug actually works in a number of ways, but the anti-inflammatory component is probably the most significant feature, in that it brings the normative balance of the secretions of the meibomian gland back to their natural state.”

Dr. Thimons said the meibomian oils actually have a high level of anti-inflammatory activity when secreting normally. “One of the reasons we use doxycycline is to help return the meibomian glands to the normal metabolism,” he said.

Paul M. Karpecki

According to Paul M. Karpecki, OD, FAAO, a Primary Care Optometry News Editorial Board member and director of research at Moyes Eye Center, Kansas City, Mo., the tetracycline antibiotics treat these conditions by decreasing cytokines and other inflammatory mediators. He said tetracyclines are particularly useful in the treatment of lid diseases, such as meibomianitis and blepharitis as well as dermatological conditions such as acne rosacea.

“For meibomian gland dysfunction, the primary problem is anti-inflammatory,” he said in an interview. “I would suggest a combination drop — drops work better for meibomianitis and ointments may be better for blepharitis.”

For recurrent corneal erosion, Dr. Karpecki said any antibiotic with low toxicity, such as the later-generation fluoroquinolones, would provide broad-based coverage.

Stephen C. Pflugfelder, MD, of the Cullen Eye Institute in Houston, added: “It has been found that the cycline antibiotics have an anti-inflammatory mechanism of action, both for the eye and systemically,” he told Primary Care Optometry News.

Medication, dosing, duration

Stephen C. Pflugfelder

Doxycycline is an especially useful cycline antibiotic for the treatment of meibomian gland dysfunction, recurrent corneal erosions and corneal ulcers, Dr. Thimons said.

“In the past, the standard dose for most clinicians has been doxycycline two times a day for 3 to 6 weeks,” he said. “Some people like to use a step-down at 3 weeks to once a day. I certainly have employed that regimen.”

For many patients, however, twice a day for a month is fine, with no need to taper the drug, he said. “The difficulty is that the long-term use of the drug has recently been implicated in the possible development of breast cancer, so many clinicians, including myself, have chosen to decrease the dosing schedule significantly,” Dr. Thimons said. “Where before I would have used twice-daily dosing for 3 to 6 weeks, now I will typically use 100 mg for a week to 2 weeks, and then cut back to 40 mg (Periostat) a day for another 2 to 3 weeks. I feel that I am achieving a very similar response clinically as far as patient resolution of their conditions.”

Dr. Karpecki said he prefers to prescribe doxycycline at 50 mg.

“I prefer 50 mg, because 100 mg seems to have too many side effects, such as gastritis, with very little added benefit,” he said. “I also like Periostat (doxycycline hyclate, CollaGenex), which is indicated for gingivitis but is actually just 20 mg of doxycycline. It seems to work very well with even less risk of phototoxicity, gastritis, chelation, issues with dairy products, etc.”

Dr. Karpecki said his normal dosage would be twice a day for 1 to 2 months, followed by once daily for 1 to 2 months.

Dr. Pflugfelder said he also generally prefers doxycycline, although he will sometimes prescribe minocycline. His use of minocycline is less frequent, however, due to side effects associated with this drug.

Halting tissue destruction

In treating corneal ulcers, some practitioners prescribe tetracyclines to slow tissue destruction.

Take-home pearls
A combination pill, doxycycline or minocycline may be effective for meibomian gland dysfunction. Doxycycline and minocycline may also be effective against corneal ulcers. Later-generation fluoroquinolones would provide broad-based coverage for recurrent corneal erosion.

According to Dr. Thimons, doxycycline is the most reliable of these antibiotics for this indication. “One of the things about tetracycline that makes it less appealing is that the four-times-daily dosing gives it a very short half-life and requires a fairly strict adherence to this regimen to achieve success,” he said. “Second, you need to be aware of the food intake issue related to the absorption of the drug, particularly with dairy products.”

Dr. Thimons said some practitioners may opt for minocycline, which has been shown to work on a once-daily dosing schedule.

“The problem with oral minocycline once daily is that it wasn’t a generic drug until recently, so it’s fairly expensive,” he said. “Also, the literature reports a slightly greater incidence of non-ocular side effects with minocycline. We’ve found that doxycycline is the most reliable, easily accessible and inexpensive drug in this category.”

Dr. Karpecki said for the more severe ulcers with a significant amount of inflammation, he uses doxycycline 50 mg twice a day. “Because it is a collagenase and MMP-9 inhibitor, it should help, and anecdotally, it seems to,” he said.

Tetracyclines and breast cancer?

Recent literature has raised concerns regarding a possible link between long-term use of these antibiotics and an increased risk of breast cancer. “The practitioner should be aware of the possible risk,” Dr. Pflugfelder said. “I have cut back on the doses and the dosing duration. For some women, I don’t prescribe them at all. I might prescribe a topical instead.”

Dr. Thimons said the study that raised these concerns looked at the development of breast cancer from the use of a number of antibiotic categories, not just the cyclines. “Use of the antibiotics produced side effects over a lifetime, so not surprisingly, we came up with numbers that were higher than we would have liked them to be,” he said. “The difficulty with the cyclines is that they are rarely used to treat acute interventional disease. So you’re not going to have a patient on it for 7 to 10 days, which is what we typically do when we’re treating a patient with a problematic preseptal cellulitis, or any of the typical conditions that we see in the office.

“It’s frequently a one-time episode, and they’re discharged from care,” he continued. “But with doxycycline, the nature of the treatment is typically chronic, so the data from the studies showed that there was an increase in breast cancer with all but one of the categories. Doxycycline was slightly higher than the others.”

While Dr. Thimons said he believes clinicians should note these concerns, he feels in cases where these drugs are truly warranted, they are still a good choice. However, clinicians should apply the recommended decrease in dosing.

“You must have a good reason to treat to justify your decision,” he said. “But if the patient’s disease is severe enough that he or she risks vision or sight-threatening problems, that also warrants the use of the agent.”

Dr. Karpecki said while he has lowered his prescribed doses for these drugs, he has still not seen enough information to merit a significant change in his prescribing habits.

“I have not seen enough science or scientific papers to change my prescribing away from tetracycline medications, other than to lower the dose, such as 50 mg or Periostat at 20 mg,” he said. “And I try to get patients off the medications sooner. But that’s the extent of the change to my prescribing until the science proves the link one way or another.”

For More Information:

• J. James Thimons, OD, FAAO, practices at Ophthalmic Consultants of Connecticut and is a Primary Care Optometry News Editorial Board member. He can be reached at 75 Kings Highway Cutoff, Fairfield, CT 06430; (203) 366-8000; fax: (203) 330-4958; e-mail: jthimons@sbcglobal.net.
• Paul M. Karpecki, OD, FAAO, is a Primary Care Optometry News Editorial Board member and director of research at Moyes Eye Center. He can be reached at Moyes Eye Center, Barry Medical Park, St. Luke’s Northland Campus, 5844 N.W. Barry Road, Ste. 200, Kansas City, MO 64154; (816) 746-9800; fax: (913) 681-5584; e-mail: paulk-vc@kc.rr.com.
• Stephen C. Pflugfelder, MD, practices at the Cullen Eye Institute in Houston. He can be reached at 6565 Fannin, NC 307, Houston, TX 77030; (713) 798-4732; fax: (713) 798-1457; e-mail: stevenp@bcm.tmc.edu. Drs. Thimons, Karpecki and Pflugfelder have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.