Q: I have a patient who has ocular/dermatologic rosacea with some severe corneal findings. His dermatologist prefers minocycline to doxycycline. Are there any real advantages or disadvantages of using one rather than the other?
A: The short answer: Both drugs have been proven effective at treating ocular rosacea, which mostly entails the same protocol as treating cutaneous rosacea. Still, doxycycline is considered preferable to minocycline for the treatment of rosacea, while minocycline is deemed the better of the two for treating acne.
But, the reasons behind these prescribing trends are more anecdotal and theoretical than based on large clinical trial. Except for a few small, decades-old studies that involved acne vulgaris patients, the two antibiotics have never been compared in a rigorous clinical trial. They evolved into their respective roles based on assumptions about their pharmacologic properties.
In the 1940s, physicians began looking for systemic ways to treat acne and gravitated toward antibiotics. They believed that the red, inflamed, pus-filled lesions were caused by bacterial infections. By the mid-1950s, tetracyclines were widely prescribed for acne; because they worked fairly well, no one questioned the mechanism of action.
Two tetracycline compoundsdoxycycline and minocyclinethat were introduced in the late 1960s and early 1970s, offered acne and rosacea patients easier dosing schedules and decreased side effects. Still, their antibiotic properties were considered operative.
In the 1980s, researchers discovered that these drugs work on acne, rosacea and related conditions, mainly through anti-inflammatory pathways. While investigating treatments for adult periodontitis, a 1983 animal study showed that minocycline inhibited tissue collagenolytic enzyme activity in ways independent of its antibacterial mechanism.1 This kicked off a whole new era in tetracycline research.
Anti-inflammatory mechanisms attributed to tetracyclines during this period include inhibition of matrix-degrading metalloproteinases (MMPs), proteolytic enzymes produced by infiltrating inflammatory cells and connective tissue cells in the periodontal matrix. Of the commercially available tetracyclines, doxycycline proved the best inhibitor of MMP activity.2 Also, doxycycline was best tolerated for long-term use.
As with any antibiotic, bacterial resistance is a worry. Although antimicrobial activity is not their primary purpose, tetracyclines are clearly associated with resistant strains of Propionibacterium acnes.3,4 P. acnes itself is not especially dangerous; however, microbes can pass resistance from one species to another.
So, minimizing resistance among all bacteria is prudent public health policy.5,6 Resistance was seen least often with minocycline, which is why it is widely indicated for acne. Bacteria do not directly cause acne, as once thought. Still, microbes do play a significant role in the disease, probably by inducing inflammatory immune response. Thus, some level of antimicrobial activity is considered beneficial.
In 1998, the FDA approved Periostat (doxycyline hyclate, CollaGenex Pharmaceuticals) for periodontal disease. (Some eye care practitioners prescribe Periostat off-label for ocular rosacea.) The dosage (20mg b.i.d.) is high enough to induce anti-inflammatory action but low enough to avoid antibacterial action and risk of bacterial resistance. Also, the lower dose minimizes side effects.
When Periostat went generic, CollaGenex re-introduced it as a 40mg, once-daily, time-released pill called Oracea, which gained FDA approval for treating rosacea in May 2006. Oracea is the drug of choice for rosacea, says Joseph Bikowski, M.D., assistant professor of dermatology at Ohio State University. However, the cost may be prohibitory. It is about $4 a pill. For that reason, some clinicians prescribe doxycycline off-label.
Minocycline is considered an acceptable second-line option, but there are more reports of adverse events than with doxycycline. Lightheadedness, loss of balance and dizziness may occur. Long-term use is associated with rare cases of a blue/black discoloration (sometimes permanent) of the sclera, teeth, skin and/or nails. Pneumonitis, lymphadenopathy, pseudotumor cerebri and an infectious mononucleosis-type reaction also have been reported.
There were reports of esophageal irritation with doxycycline hyclate, but a newer form of the drug, doxycycline monohydrate, which has a milder pH balance, seems to have solved this problem. A major concern with doxycycline is phototoxicity, a risk that appears to be dose dependent. Patients who fail to respond to standard doses may need to take up to 100mg or more per day; phototoxicity incidence increases to 3% for 100mg/day, 20% for 150mg/day and 42% for 200mg/day. All tetracyclines carry warnings of photosensitivity, but doxycycline has the highest risk of this side effect.
High-fat/high-protein foods, especially dairy products, and antacids can interfere with absorption of these drugs, so they should be taken one hour before or two hours after meals. Mineral supplements, such as aluminum, zinc, bismuth or magnesium, can have the same effect and should be avoided. A lot of older patients with macular degeneration will be taking zinc, so thats something to watch out for, says Bruce Onofrey, O.D., R.Ph., of Albuquerque, N.M.
Be warned: Breast cancer concerns may arise when discussing tetracyclines. A 2004 JAMA study generated headlines when it linked long-term antibiotic use to higher risk of breast cancer.7 Despite widespread publicity, the study did not establish causality. Periostat researchers investigated the issue prior to FDA approval and uncovered no direct carcinogenic effects.
1. Golub LM, Lee HM, Lehrer G, et al. Minocycline reduces gingival collagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action. J Periodontal Res 1983 Sep;18(5):516-26.
2. Burns FR, Stack MS, Gray RD, Paterson CA. Inhibition of purified collagenase from alkali-burned rabbit corneas. Invest Ophthalmol Vis Sci. 1989 Jul;30(7):1569-75.
3. Cooper AJ. Systematic review of Propionibacterium acnes resistance to systemic antibiotics. Med J Aust 1998 Sep 7;169(5):259-61.
4. Leyden JJ, McGinley KJ, Cavalieri S, et al. Propionibacterium acnes resistance to antibiotics in acne patients. J Am Acad Dermatol 1983 Jan;8(1):41-5.
5. Dahl MV. Pathogenesis of rosacea. Adv Dermatol 2001;17:29-45.
6. Levy R, Huang E, Roling D, et al. Effect of antibiotics on the oropharyngeal flora in patients with acne. Arch Dermatol. 2003 Apr;139(4):467-71.
7. Velicer CM, Heckbert SR, Lampe JW, et al. Antibiotic use in relation to the risk of breast cancer. JAMA 2004 Feb 18;291(7):827-35.
Vol. No: 144:02Issue:
2/15/2007