Doxycycline vs. Minocycline for the Management of Acne

September 2011 | Volume 10 | Issue 9 | Editorials | 965 | Copyright © September 2011

Alan R. Shalita MD, Guy F. Webster MD PhD, Mitchell S. Wortzman PhD, Diane Nelson BSN MPH


Approximately 40 years ago, immediate release (IR) tablet and capsulated delivery forms of minocycline and doxycycline were made available for prescription. These dosage forms resulted in a rapid release of drugs in the digestive tract and subsequently into the systemic circulation, with peak serum concentrations being reached several hours after administration. While the IR dosage forms are associated with certain adverse events (AEs), there are well-known methodological challenges in determining comparative rates, and even types, of AEs for drugs. Voluntary case reporting is non-systematic and is therefore limited in obvious ways, and AE reports from clinical trials suffer from variability of treatment protocols among agents studied, small numbers of participants, short duration of follow up and selective eligibility criteria for study populations. Nevertheless, clinical trial AEs are more systematically reported and are thought to be most useful in profiling the most common AEs. With respect to the IR formulations of doxycycline and minocycline, clinical trial estimates indicate the most common AEs are esophagitis and photosensitivity (doxycycline), gastrointestinal upsets (both drugs) and acute vestibular events (minocycline).1


The AE rates for both IR antibiotics are relatively low and each is well-tolerated.1 Nevertheless, in the interests of improving safety and patient compliance, new extended release formulations of minocycline and doxycycline have been made available in recent years that moderate and better control the rate of dissolution and bioavailability, resulting in less gastrointestinal and vestibular disorders.2-7


In the recent publication by Kircik,8 AEs observed for enteric-coated doxycycline are reviewed in conjunction with those observed for traditional IR dosage forms of minocycline and doxycycline. Additionally, comparisons of effectiveness are made for IR minocycline and doxycycline suggesting that there is no difference between the two drugs. With regard to published studies evaluating the effectiveness of these older formulations, the author addresses studies published between 1976 and 2005, which precedes the approval of extended release (ER) minocycline. Although the author briefly mentions ER minocycline (SOLODYN® (minocycline HCl, USP) Extended Release Tablets, Medicis, Scottsdale, AZ), which was introduced in 2006, his review neglected to include six important studies that were conducted for this FDA-approved dosage form.3-5


In the author's review, a number of non-comparative studies are referenced which consisted of variable patient counts and employed IR minocycline utilizing a variety of dosage strengths.8,9 The author then highlights three studies conducted with head-to-head comparisons of doxycycline and IR minocycline. One comparison study occurred in a small number of patients (n=64) with a dosage regimen of 50 mg IR minocycline twice per day for four weeks and then once per day for the next eight weeks. Two additional studies involved a smaller number of patients (n=18 and 34, respectively), and in one of these studies patients used salicylic acid 5% and resorcinol 5% in addition to IR minocycline or doxycycline. Kircik concluded that IR formulations of doxycycline and minocycline do not differ in effectiveness on the basis of small studies that were severely underpowered for the purpose of showing equivalence with IR antibiotics. The author's conclusions are not supported by reliable statistical analysis. These comparisons did not contemplate ER formulations.


Extended release minocycline was the first systemic antibiotic approved by the U.S. Food and Drug Administration (FDA) for the treatment of only inflammatory lesions of non-nodular moderate- to-severe acne vulgaris in patients 12 years of age and older. Overlooked in this review were three prospective (one phase II and two phase III), multicenter, randomized, double-blinded, placebo-controlled clinical trials investigating the safety and effectiveness of ER minocycline in more than 1000 patients ≥12 years old with moderate-to-severe facial acne, as well as three bioavailability studies, all published in 2006.3-5 In summary, these studies demonstrated that ER minocycline (a) moderates the rate of minocycline release and peak serum concentration compared to non-modified release minocycline,3 (b) is not bioequivalent to non-modified release minocycline products,3 (c) has an FDA approved dosage regimen of ~1 mg/kg once per day (which is lower than traditionally dosed IR minocycline at 100 mg twice daily),4 (d) demonstrates a similar incidence of AEs when compared to placebo (ER minocycline 56.2%, placebo 54.1%), including those of a transient vestibular nature,5 (e) is unaffected by foods or dairy intake3 and (f) significantly reduced the percentage of inflammatory lesion counts in patients when compared to placebo treatment.5


When comparing products, it may be useful to the practicing clinician to include studies that lend themselves to rigorous meta-analysis standards, wherein results are combined from similar studies that meet accepted criteria such as comparable formulations, randomization, double-blindness and placebo-controlled trials with adequate numbers of patients, or in head-to-head clinical studies meeting these same guidelines. The studies cited in this review did not meet these criteria, and as of the day of this letter's composition no head-to-head study comparing minocycline (for either the IR and ER formulations) vs. doxycycline exists which meet these standards.


When prescribing an anti-acne medication, the clinician is likely confronted with two important questions: (1) the likelihood of his patient experiencing AEs and (2) the medication's known effectiveness for the condition being treated. A review that compares two different drugs for the same use would potentially be valuable to the clinician, provided a thorough and comprehensive review of the literature is conducted for both medications and differences with regard to formulations (e.g., immediate release vs. extended release) are identified in a consistent manner throughout.