isotretinoin
Regulatory sources consulted
Approved indications
- Severe nodular or conglobate acne, or acne at risk of permanent scarring, resistant to adequate systemic antibacterial and topical treatment.
Contraindications
Absolute
- Pregnancy, planned pregnancy, breastfeeding, or a woman of childbearing potential who does not meet the Pregnancy Prevention Program.
- Hepatic impairment, excessive hyperlipidemia, hypervitaminosis A, tetracycline treatment, or hypersensitivity; peanut or soy allergy for this formulation.
Clinical warnings
- Major warning · Potent human teratogen: effective contraception from 1 month before, during, and for 1 month after treatment; pregnancy testing before, ideally monthly during treatment, and 1 month afterward. Stop and refer immediately if pregnancy occurs. — CIMA/AEMPS, ficha técnica 82566
- Major warning · Monitor mental state and stop or assess for depression, suicidal ideation, aggression, or psychosis; monitor lipids and liver function and watch for pancreatitis, intracranial hypertension, and visual changes. Suicidal ideation or behavior and psychosis have unknown frequency. — CIMA/AEMPS, ficha técnica 82566
- Do not donate blood during treatment or for 1 month afterward. Avoid waxing, aggressive dermabrasion, and cutaneous laser during treatment and for at least 6 months afterward. — CIMA/AEMPS, ficha técnica 82566
Drug interactions
- HighTetracyclines
Mechanism: They increase the risk of benign intracranial hypertension.
Recommendation: Concomitant use is contraindicated.
CIMA/AEMPS, ficha técnica 82566https://cima.aemps.es/cima/dochtml/ft/82566/FT_82566.html
- HighVitamin A or other retinoids
Mechanism: They increase the risk of hypervitaminosis A and retinoid toxicity.
Recommendation: Do not use together.
CIMA/AEMPS, ficha técnica 82566https://cima.aemps.es/cima/dochtml/ft/82566/FT_82566.html
- ModerateTopical anti-acne keratolytics or exfoliants
Mechanism: They may increase local irritation.
Recommendation: Avoid concomitant use.
CIMA/AEMPS, ficha técnica 82566https://cima.aemps.es/cima/dochtml/ft/82566/FT_82566.html
Adverse events
Common (≥1%)
Dry skin · Cheilitis · Epistaxis and nasal dryness · Conjunctivitis and dry eyes
Rare but serious
Anaphylactic reaction · Benign intracranial hypertension · Pancreatitis · Hepatitis
Pregnancy and lactation
Contraindicated during pregnancy and breastfeeding. Fetal exposure causes severe malformations and increases miscarriage; stop and refer if pregnancy occurs.
Recent literature (PubMed)
Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. The objective of this study was to provide evidence-based recommendations for the management of acne. A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. Analysis is based on the best available evidence at the time of the systematic review. These guidelines provide evidence-based recommendations for the management of acne vulgaris.
Acne vulgaris is an inflammatory disease of the pilosebaceous unit of the skin that primarily involves the face and trunk and affects approximately 9% of the population worldwide (approximately 85% of individuals aged 12-24 years, and approximately 50% of patients aged 20-29 years). Acne vulgaris can cause permanent physical scarring, negatively affect quality of life and self-image, and has been associated with increased rates of anxiety, depression, and suicidal ideation. Acne vulgaris is classified based on patient age, lesion morphology (comedonal, inflammatory, mixed, nodulocystic), distribution (location on face, trunk, or both), and severity (extent, presence or absence of scarring, postinflammatory erythema, or hyperpigmentation). Although most acne does not require specific medical evaluation, medical workup is sometimes warranted. Topical therapies such as retinoids (eg, tretinoin, adapalene), benzoyl peroxide, azelaic acid, and/or combinations of topical agents are first-line treatments. When prescribed as a single therapy in a randomized trial of 207 patients, treatment with tretinoin 0.025% gel reduced acne lesion counts at 12 weeks by 63% compared with baseline. Combinations of topical agents with systemic agents (oral antibiotics such as doxycycline and minocycline, hormonal therapies such as combination oral contraception [COC] or spironolactone, or isotretinoin) are recommended for more severe disease. In a meta-analysis of 32 randomized clinical trials, COC was associated with reductions in inflammatory lesions by 62%, placebo was associated with a 26% reduction, and oral antibiotics were associated with a 58% reduction at 6-month follow-up. Isotretinoin is approved by the US Food and Drug Administration for treating severe recalcitrant nodular acne but is often used to treat resistant or persistent moderate to severe acne, as well as acne that produces scarring or significant psychosocial distress. Acne vulgaris affects approximately 9% of the pop
In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some "off-label" use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.
Perioral dermatitis is a common cutaneous condition characterized by acneiform facial eruptions often with an eczematous appearance. A granulomatous subtype exists in addition to the classic variant. While topical corticosteroids have been largely implicated in this condition, its etiology is not completely understood. Using the keywords "corticosteroids," "dermatology," "fusobacteria," "perioral dermatitis," and "periorificial dermatitis," we searched the databases PubMed, MEDLINE, and EMBASE to find the relevant literature. Only articles in English were chosen. The level of evidence was evaluated and selected according to the highest level working our way downwards using the Oxford Centre of Evidence-Based Medicine 2011 guidance. This systematic review found the strongest evidence to support topical corticosteroid misuse as the principal causative factor in the pathogenesis of perioral dermatitis. In terms of treatment, further research is required to robustly investigate promising treatment options including tetracyclines, topical metronidazole, topical azelaic acid, adapalene gel, and oral isotretinoin.
Acne vulgaris is very common and can have significant negative impact on people. While sometimes a transient problem, acne may persist for many years and often leads to permanent scars or pigment changes. Guidelines unanimously advise topical treatments as first-line, although differ in recommending either topical benzoyl peroxide or topical retinoid (mainly adapalene) alone or in combination. Guidance published by the National Institute for Health and Care Excellence advises counselling patients regarding avoidance of skin irritation when starting topical treatments and promoting adherence (treatments take 6-8 weeks to work). Oral antibiotics are currently overprescribed for acne but have a role when coprescribed with a non-antibiotic topical treatment. Hormonal treatments, such as the combined contraceptive pill, are also effective and there is growing evidence for the use of spironolactone for women with persistent acne. Recent guidance from the Medicines and Healthcare products Regulatory Agency regarding isotretinoin has implications for specialist prescribing and monitoring, and increasing public awareness of potential risks of mental health problems and sexual dysfunction. Although acne is associated with psychiatric disorder, the mental health effects of isotretinoin remain controversial.