Subject: Isotretinoins PA 118-A P08-2025

Drug

Isotretinoins (All Oral)

ABSORICA  (isotretinoin)

ABSORICA LD®  (isotretinoin)

ACCUTANE  (isotretinoin)

AMNESTEEM  (isotretinoin)

CLARAVIS  (isotretinoin)

ZENATANE  (isotretinoin)

Policy:

Indications

FDA-approved Indications

Absorica, Absorica LD

Absorica and Absorica LD are indicated for the treatment of severe recalcitrant nodular acne in non-pregnant patients 12 years of age and older with multiple inflammatory nodules with a diameter of 5 mm or greater. Because of significant adverse reactions associated with its use, Absorica and Absorica LD are reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics.

Limitations of Use

If a second course of Absorica/Absorica LD therapy is needed, it is not recommended before a two-month waiting period because the patient’s acne may continue to improve following a 15 to 20-week course of therapy.

Accutane, Amnesteem, Claravis, Zenatane

Isotretinoin is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, isotretinoin should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, isotretinoin is indicated only for those patients who are not pregnant, because isotretinoin can cause life-threatening birth defects.

A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off isotretinoin. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth.

Compendial Uses

Acne – severe⁸

Cutaneous T-Cell Lymphoma (CTCL) (e.g., mycosis fungoides, Sézary syndrome)⁶

Keratosis follicularis (Darier Disease) – severe⁸

Keratosis Palmaris et Plantaris - severe⁶

Lamellar ichthyosis – severe skin involvement⁶

Neuroblastoma⁸

Pityriasis rubra pilaris⁶

Rosacea – severe refractory⁸

Squamous Cell Cancers – to reduce the development of precancers and skin cancers in high risk patients⁸

Transient acantholytic dermatosis (Grover’s Disease) – severe⁸

Coverage Criteria

Acne Vulgaris, Rosacea

Authorization may be granted when the patient has a diagnosis of severe recalcitrant nodular acne vulgaris, severe acne vulgaris, OR severe refractory rosacea when ALL of the following criteria are met:

• The patient has tried and had an inadequate treatment response to ANY topical acne product AND an oral antibiotic. [Note: Topical products include salicylic acid, benzoyl peroxide, azelaic acid, adapalene, tretinoin, tazarotene, clindamycin, erythromycin, or metronidazole for rosacea. Oral antibiotics include minocycline, doxycycline, tetracycline, erythromycin, trimethoprim-sulfamethoxazole, trimethoprim, azithromycin.]
• Treatment will be limited to 40 weeks (2 courses) or less AND with at least 8 weeks between each course.

Neuroblastoma, Cutaneous T-cell Lymphoma (CTCL), Squamous Cell Cancers, Grover’s Disease, Darier Disease, Lamellar Ichthyosis, Pityriasis Rubra Pilaris, Keratosis Palmaris et Plantaris

Authorization may be granted when the patient has a diagnosis of neuroblastoma, cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sézary syndrome), is at high risk for developing skin cancer (squamous cell cancers), transient acantholytic dermatosis (Grover’s Disease), keratosis follicularis (Darier Disease), lamellar ichthyosis, pityriasis rubra pilaris, OR keratosis palmaris et plantaris.

Duration of Approval (DOA)

• 118-A: DOA 12 months

Place of Service:

Outpatient

The above policy is based on the following references:

1. Absorica, Absorica LD [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; June 2023.
2. Accutane [package insert]. Scottsdale, AZ: JG Pharma Inc.; September 2022.
3. Amnesteem [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; June 2024.
4. Claravis [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; August 2022.
5. Zenatane [package insert]. Princeton, NJ: Dr. Reddy’s Laboratories, Inc.; September 2022.
6. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Waltham, MA: UpToDate, Inc.; 2025. https://online.lexi.com. Accessed July 15, 2024.
7. Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; 2025. https://online.lexi.com. Accessed July 15, 2025.
8. Micromedex® (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com/ (cited: 07/15/2025).
9. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30.
10. National Institute of Arthritis and Musculoskeletal and Skin Diseases. http://www.niams.nih.gov/Health_Info/Rosacea/default.asp#6. Accessed July 15, 2025.
11. Del Rosso JQ, Thiboutot D, Gallo R, et al. Consensus recommendations from the American acne & rosacea society on the management of rosacea, Part 3: A status report on systemic therapies. CUTIS. 2014;93:134-38.
12. Neuroblastoma Treatment. National Cancer Institute at the National Institute of Health. https://cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#_707_toc. Accessed July 15, 2025.
13. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Squamous Cell Skin Cancer. Version 2.2025. February 7, 2025. Available at: www.NCCN.org. Accessed July 15, 2025.
14. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Primary Cutaneous Lymphomas. Version 3.2025. June 10, 2025. Available at: www.NCCN.org. Accessed July 15, 2025.
15. American Osteopathic College of Dermatology. Grover's Disease. http://www.aocd.org/?page=GroversDisease. Accessed July 15, 20245
16. NIH National Center for Advancing Translational Sciences. Genetic and Rare Diseases Information Center. Darier disease. https://rarediseases.info.nih.gov/diseases/6243/darier-disease. Accessed July 15, 2025.
17. Darier Disease. American Osteopathic College of Dermatology. http://www.aocd.org/skin/dermatologic_diseases/darier_disease.html. Accessed July 15, 2025.
18. NIH National Center for Advancing Translational Sciences. Genetic and Rare Diseases Information Center. Lamellar ichthyosis. https://rarediseases.info.nih.gov/diseases/10803/lamellar-ichthyosis. Accessed July 15, 2025.
19. NIH National Center for Advancing Translational Sciences. Genetic and Rare Diseases Information Center. Pityriasis rubra pilaris. https://rarediseases.info.nih.gov/diseases/7401/pityriasis-rubra-pilaris. Accessed July 15, 2025.
20. Pityriasis Rubra Pilaris. American Osteopathic College of Dermatology. http://www.aocd.org/?page=PityriasisRubraPil. Accessed July 15, 2025.
21. NIH National Center for Advancing Translational Sciences. Genetic and Rare Diseases Information Center. Keratosis Palmaris Et Plantaris-Clinodactyly Syndrome. https://rarediseases.info.nih.gov/diseases/16766/x. Accessed July 17, 2025.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

December 13, 2025