Dermatology Express Report™ Fax

Publication date: 2006-07-15

Weight-based Dosing of a Novel Antibiotic for Moderate-to-Severe Acne Vulgaris Offers Potential for Improved Safety and Tolerability

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

Expert Commentary

James Q. Del Rosso, DO, FAOCD, Clinical Associate Professor, Department of Dermatology, University of Nevada School of Medicine, Las Vegas, Nevada

The recent approval of minocycline extended-release tablets (Solodyn) by the Food and Drug Administration (FDA) offers a major advancement for treating 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 the vestibular adverse effects that have been associated with minocycline administration.¹ Unlike immediate-release minocycline formulations, minocycline extended-release tablets offer a unique pharmacokinetic delivery that, when dosed on a 1 mg/kg weight-basis,² provides the lowest effective dose of minocycline for treating moderate-to-severe acne vulgaris. 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 anti-biotic approved by the FDA as first-line therapy for the treatment of acne.²

Systemic antibiotic therapy is indicated in the treatment of moderate-to-severe inflammatory acne, or acne considered emotionally burdensome for the patient for psychological or social reasons.³ Physicians have used erythromycin, tetracycline, doxycycline, and minocycline to treat acne vulgaris for decades. However, until recently, these antibiotics had not been evaluated in pivotal phase 3 clinical studies for the systemic treatment of acne. Erythromycin therapy may be associated with intolerable gastrointestinal side effects including nausea, vomiting, diarrhea, abdominal pain, and anorexia.³ Tetracycline should be administered on an empty stomach as the presence of food or dairy products may hinder its absorption. Consequently, tetra-cycline 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 tetra-cycline to produce gastrointestinal side effects.⁴ However, doxycycline may be limited by dose-related phototoxicity in some patients,⁵ and minocycline may be associated with vestibular adverse events and tissue pigmentation.⁶ Vestibular adverse events are the most common reason for treatment discontinuation of minocycline.^7,8

The clinical development of minocycline extended-release tablets was based on 2 proposed hypotheses: first, that the efficacy of minocycline in treating acne vulgaris was not related to its serum concentrations; and second, 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 pilose-baceous unit,⁹ where sebum serves as a growth medium for Propionibacterium acnes (P. acnes) within the follicles. The extent of systemic minocycline bioavailability in acne is less important than the lipophilic property of the molecule, as accumulation of greater minocycline levels in the pilosebaceous unit is believed to provide a clinically effective level of P. acnes reduction.¹⁰ The pharmacokinetic delivery of minocycline extended-release tablets avoids the more rapid increase in serum levels observed with immediate-release minocycline. A more rapid increase in the serum level of minocycline may influence the potential for vestibular adverse events (eg, dizzine