Dermatology Express Report™

Publication date: 2006-07-14

Safety and Efficacy of Weight-based Dosing of a Novel Formulation of Minocycline for Moderate-to-Severe Acne Vulgaris

This report was reviewed for medical and scientific accuracy by Amy S. Paller, MD, Professor and Chair of Dermatology, Professor of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Expert Commentary

James J. Leyden, MD, Professor of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania

The recent approval of minocycline extended-release tablets (Solodyn) by the Food and Drug Administration (FDA) offers new insights into the treatment of moderate-to-severe acne vulgaris. Minocycline extended-release tablets were formulated to provide optimal efficacy in treating moderate-to-severe acne vulgaris while potentially minimizing vestibular adverse effects. Unlike immediate-release minocycline formulations, minocycline extended-release tablets offer a sustained release with lower peak plasma levels resulting in a lower incidence of vestibular side effects.¹ In addition, minocycline extended-release tablets are administered once daily, thus offering the potential to enhance patient compliance. Minocycline extended-release tablets are indicated for the treatment of inflammatory lesions of non-nodular moderate-to-severe acne vulgaris and represent the first oral systemic antibiotic approved by the FDA as first-line therapy for the treatment of acne.¹

Physicians have used systemic antibiotics such as erythromycin, tetracycline, doxycycline, and minocycline to treat acne vulgaris for decades. However, none of these agents have been evaluated in classical FDA clinical trials in which safety and efficacy are established. Erythromycin therapy may be associated with intolerable gastrointestinal side effects including nausea, vomiting, diarrhea, abdominal pain, and anorexia.² Erythromycin is extensively metabolized by cytochrome P450 CYP3A and also inhibits CYP3A; therefore, drug interactions may occur when erythromycin is concomitantly administered with medications such as azole antifungal agents (eg, ketoconazole) and antiepileptic agents (eg, carbamazepine, phenobarbital, phenytoin) known to induce CYP3A.³ Moreover, Propionibacterium acnes (P. acnes) sensitivity to erythromycin and related agents has decreased greatly over the past 20 years to the point that clinical resistance can occur. Tetracycline must be administered on an empty stomach as the presence of food or dairy products may hinder its absorption. Consequently, tetracycline may be associated with minor gastrointestinal side effects including nausea, vomiting, and diarrhea. Doxycycline and minocycline are absorbed well, and minocycline is less likely than erythromycin and tetracycline to produce gastrointestinal side effects.⁴ Compared with doxycycline and tetracycline, minocycline has been associated with the greatest log reduction of P. acnes, most rapid onset of effect, and greatest residual reduction in P. acnes.⁵ Moreover, minocycline exhibits the lowest prevalence of P. acnes resistance compared with doxycycline, erythromycin, and tetracycline.6 Resistance of P. acnes to oral antibiotics (eg, erythromycin, tetracycline) has been correlated with acne treatment failure.^7–9 Doxycycline may be limited by dose-related phototoxicity in some patients,¹⁰ and minocycline may be associated with vestibular adverse events and tissue pigmentation.¹¹ Vestibular adverse events are an important reason for treatment discontinuation.^12,13

The clinical development of minocycline extended-release tablets was based on 2 proposed hypotheses: that the efficacy of minocycline in treating acne vulgaris was not related to its serum concentrations and that the high peak serum concentrations of minocycline were responsible for the acute vestibular adverse events. The highly lipophilic property of minocycline is well-suited for penetration into lipid-rich tissues such as the pilosebaceous unit.⁵ The extent of minocycline bioavailability may be less im