Dermatology Education Initiative - Acne Treatments Express Report

Based on Data Presented at the 31^st Hawaii Dermatology Seminar, March 3-9, 2007, Maui, Hawaii

Publication date: 2007-05-14

Treatment of Moderate-to-Severe Acne Vulgaris: Optimal Dosing of Oral Antibiotics

This report was reviewed for medical and scientific accuracy by Mark A. Gendreau, MD, MS, Associate Vice Chairman, Senior Staff Physician, Lahey Clinic, Burlington, Massachusetts.

This Acne Treatments Express Report™ reviews new data on minocycline extended-release tablets presented at the 31^st Hawaii Dermatology Seminar. This data supports that the optimal dose of minocycline extended-release tablets is 1 mg/kg/day, and when taken at this dose, results in significant reductions in inflammatory lesions and significant improvement in ESGA scores in patients with moderate-to-severe acne vulgaris.

Expert Commentary

Hilary E. Baldwin, MD, Vice Chair and Associate Professor of Clinical Dermatology, Department of Dermatology, State University of New York, Brooklyn, New York

Oral antibiotics such as erythromycin, tetracycline, doxycycline, and minocycline have been used for decades to treat acne vulgaris, a dermatologic condition that affects an estimated 40 to 50 million individuals in the United States. ¹ These systemic agents are effective in the treatment of acne due to both their antibacterial and anti-inflammatory effects. ² Systemic antibiotic therapy is typically used first-line to treat moderate-to-severe acne vulgaris and second-line (after the failure of topical combinations) in less severe cases. ^2,3 However, side effects commonly limit the use of these agents-erythromycin therapy may be associated with gastrointestinal intolerance; ⁴ tetracycline with moderate-to-severe photosensitivity and gastrointestinal intolerance; doxycycline with esophagitis and dose-related phototoxicity; ^5,6 and minocycline with vestibular adverse events and, rarely, skin discoloration. ^7,8 The use of erythromycin is further limited by its propensity to interact with other drugs (eg, ketoconazole, carbamazepine, phenobarbital, phenytoin) by way of the cytochrome P450 enzyme system. ⁹ Increasing Propionibacterium acnes resistance to erythromycin has rendered it largely ineffective in its role as an antibacterial agent although it retains its anti-inflammatory effects. ¹⁰

Despite their use for more than 30 years in the treatment of acne, these agents have never been evaluated in classical US Food and Drug Administration (FDA) clinical trials in which safety and efficacy are established. Rather, safety and efficacy have been established by clinical experience rather than rigorous clinical trials and importantly, dose-response studies have not been performed. ¹¹

In 2006, an extended-release formulation of minocycline (Solodyn) was approved by the FDA for the treatment of inflammatory lesions of non-nodular moderate-to-severe acne vulgaris, becoming the first oral systemic antibiotic to receive FDA approval as first-line therapy for the treatment of acne vulgaris. ¹² Studies leading to its FDA approval included the first dose-response studies for oral antibiotics in the treatment of acne vulgaris. This extended-release formulation of minocycline was developed to provide optimal efficacy in treating moderate-to-severe acne vulgaris while potentially minimizing vestibular adverse events (eg, dizziness, nausea, tinnitus, vertigo, or vomiting) commonly associated with immediate-release minocycline. A more rapid increase in the serum level of minocycline may influence the potential for vestibular adverse events. ¹³

Compared with immediate-release minocycline formulations, pharmacokinetic studies have shown that minocycline extended-release tablets offer a sustained release with lower peak plasma levels and lower overall drug exposure (as measured by area-under-the-curve calculations) resulting in a lower incidence of vestibular adverse events. Peak concentrations achieved following the administration of minocycline extended-release tablets are lower and occur later than those following the administration of immediate-release minocycline (C_max, 2.63 vs 2.