ARTICLE: Advances in Oral Isotretinoin Therapy

May 2021 | Volume 20 | Issue 5 | Supplement Individual Articles | s5 | Copyright © May 2021

Published online April 23, 2021

Madison Jones BA,a April W. Armstrong MD MPH,a Hilary Baldwin MD,b Linda Stein Gold MD,c Leon H. Kircik MDd

aDepartment of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA
bDepartment of Dermatology, Rutgers Robert Wood Johnson Medical Center, New Brunswick, NJ; The Acne Treatment and Research Center, Brooklyn, NY
cDepartment of Dermatology, Detroit, MI; Division of Dermatology, West Bloomfield, MI
dIcahn School of Medicine at Mount Sinai, New York, NY; Indiana University Medical Center, Indianapolis, IN; Physicians Skin Care, PLLC; DermResearch, PLLC; Skin Sciences, PLLC, Louisville, KY

Since its approval in 1982, oral isotretinoin has revolutionized acne therapy. However, oral isotretinoin use has long been associated with challenges of variable bioavailability and food dependence. It is recommended to ingest oral isotretinoin with a high-fat meal in order to maximize absorption, but many patients fail to adhere to this recommendation. This may lead to inadequate isotretinoin absorption levels. Patients who fail to achieve isotretinoin target cumulative dose are more likely to experience symptom relapse. To address the challenge of traditional isotretinoin variable bioavailability, subsequent isotretinoin formulations have attempted to improve its absorption abilities. In 2014, an isotretinoin formulation utilizing Lidose technology, known as Absorica, showed significant improvements in absorption levels compared to traditional oral isotretinoin in the fasted state. In 2019, isotretinoin absorption levels were further advanced in a new formulation approved by the FDA known as Absorica LD. Utilizing advanced micronization technology that physically reduces the size of the drug molecule, Absorica LD exhibits twice the absorption levels of Absorica under fasting conditions. In the fed state, Absorica LD achieves similar plasma levels to Absorica with a 20 percent lower dose. Absorica LD also produces consistent serum isotretinoin levels irrespective of gastrointestinal contents. By eliminating the “food effect” seen in traditional oral isotretinoin, Absorica LD has the potential to improve patient adherence and long-term patient outcomes.

J Drugs Dermatol. 20:5(Suppl):s5-11.


Before isotretinoin, no other acne therapy targeted all four pathogenesis factors of acne (including hyper-keratinization, sebum production, Cutibacterium acnes proliferation, and inflammation).1,2 Rather, other non-isotretinoin treatments for acne are often used in combination to address multiple aspects of acne pathogenesis at once.3 Isotretinoin, available in the US for almost four decades, is an oral retinoid recommended as a first-line treatment option for treating severe nodular acne.3 In addition to severe nodular acne, oral isotretinoin is used for the treatment of moderate acne that is treatment-resistant or for the management of acne that causes physical scarring or psychosocial distress, or both.3 Over time, oral isotretinoin has revolutionized the management of severe and recalcitrant acne patients due to its ability to markedly induce acne clearance coupled with its ability to achieve prolonged remission.4,5 Isotretinoin is the only treatment for which a single course of therapy has demonstrated complete or near-complete clearance of acne lesions and prolonged remission in the majority of patients with severe recalcitrant nodular acne.4,5

Although traditional oral isotretinoin has transformed acne management, its administration has faced several challenges. Notably, the bioavailability of traditional oral isotretinoin is variable and highly dependent on food administration. Isotretinoin, like other vitamin A derivatives, is a highly lipophilic molecule and its absorption is enhanced by a high-fat meal.6-8 Because of this, maximal absorption of traditional isotretinoin depends on consumption of a high-fat, high calorie meal. Pharmacokinetics of traditional isotretinoin were performed with a standardized high-fat, high-calorie meal containing 50 grams of fat and 800 to 1000 calories.7,9 FDA guidance in 2002 recommended this test meal should derive approximately 150, 250, and 500 to 600 calories from protein, carbohydrates, and fat, respectively.9 When taking traditional isotretinoin without a high-fat meal, fasting isotretinoin plasma levels can be 60 percent lower than fed conditions.8 Furthermore, peak plasma concentrations of traditional oral isotretinoin between fed and fasted conditions can vary by a factor of nearly threefold, which may potentially affect both efficacy and safety.6