The use of isotretinoin for acne – an update on optimal dosing, surveillance, and adverse effects

ABSTRACT

Introduction

Acne is a chronic, inflammatory, and immune mediated disease of pilosebaceous unit, highly prevalent in adolescents. It involves face, trunk, and back; may leave scars and affect quality of life. Early, effective, and safe treatment is the key for disease resolution. Oral isotretinoin is the unique treatment for cure or prolonged remission for moderate and severe acne, preventing psychosocial impact and scars. It inhibits sebaceous glands activity and has anti-inflammatory and immunoregulatory properties.

Areas covered

We performed a comprehensive literature search on PubMed database, up to March 2020, regarding oral isotretinoin for acne treatment. We synthetized data about acne pathogenesis and mechanism of action, efficacy, and safety of isotretinoin.

Expert opinion

This drug is effective, despite common, controllable, and reversible mucocutaneous side effects. Serious adverse events are rare and represent individual reactions. Teratogenicity is the most severe, requiring rigorous control. We believe that no other therapeutic option, even topicals combined to oral antibiotics accomplish same results. Recurrence after treatments other than isotretinoin is the rule, prolonging risk of scars, compromising skin appearance, and causing emotional distress in teenagers. If there is no absolute contraindication, isotretinoin should be the first line treatment for moderate to severe inflammatory acne.

KEYWORDS:

• Isotretinoin
• product surveillance
• post-marketing
• clinical efficacy
• therapeutics
• acne vulgaris
• adverse effects
• inflammation

Article highlights

• Acne is an impacting disease for adolescents.

• Beyond known mechanisms involved in acne pathogenesis, there are additional factors, which may also influence its chronic evolution, including stress, drugs, oral supplements, and diet in selected patients.

• It is important to treat acne as early and as effectively as possible to avoid scars and psychological sequelae.

• There are many topical but only three different sets of systemic drugs (antibiotics, antiandrogens and isotretinoin) available for treatment, usually in combination for inflammatory acne, except when isotretinoin is prescribed.

• To now, oral isotretinoin is the only drug capable of cure or prolonged remission of moderate to severe acne, when prescribed as single therapy, improving skin appearance and quality of life.

• Off label low daily doses variable duration of the treatment have been used, with less side effects, same efficacy and better adherence.

• Teratogenicity requires attention and the use of two effective contraceptive measures is mandatory, starting one month before the treatment up to one month after drug interruption.

• Common adverse events, as mucocutaneous, are dose dependent, easily managed with early and adequate orientation and use of emollients.

• Lab tests should be requested at baseline and repeated after two months. According to recent literature evidence, further repetition is necessary only if alterations are detected. Increase of LDL-cholesterol, triglycerides, and transaminases are uncommon with low daily dose and are reversible when they follow.

• Serious adverse events, including depression and inflammatory bowel disease, are rare and individual and do not justify excessive warning and concern.

• There is no psychiatric contraindication for isotretinoin. Acne is a trigger for depression during adolescence.

• Considering 38 years’ experience, studying and prescribing oral isotretinoin, it is opinion of the first author (EB) that if there is no real contraindication, including the risk of a pregnancy, this drug should be considered the first line therapy for moderate to severe acne.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer has declared recieving research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Alvotech, Leo Pharma, BMS, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, Abbvie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate and National Psoriasis Foundation. They also consult for Guidepoint Global, Gerson Lehrman and other consulting organizations. They have also disclosed working for www.DrScore.com, and Causa Research. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.