Subject: Isotretinoins PA Policy 118-A 08-2022

Drug

ISOTRETINOINS (ALL ORAL)

ABSORICA, ABSOICA LD  (isotretinoin)

ACCUTANE  (isotretinoin)

AMNESTEEM  (isotretinoin)

CLARAVIS  (isotretinoin)

MYORISAN  (isotretinoin)

ZENATANE  (isotretinoin)

Policy:

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, Myorisan, 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 female patients who are not pregnant, because isotretinoin can cause severe 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 – refractory⁸
Cutaneous T-Cell Lymphoma (CTCL) (e.g., mycosis fungoides, Sézary syndrome)⁷
Keratosis follicularis (Darier Disease) – severe⁸
Lamellar ichthyosis – severe skin involvement⁷
Neuroblastoma⁸
Pityriasis rubra pilaris⁷
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
The requested drug will be covered with prior authorization when the following criteria are met:
     •   The patient has any of the following diagnoses: A) severe recalcitrant nodular acne vulgaris, B) refractory acne vulgaris, C) severe refractory rosacea
          AND
             o   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.]
                  AND
             o   Treatment will be limited to 40 weeks (2 courses) or less AND with at least 8 weeks between each course
     OR
     •   The patient has any of the following diagnoses: A) neuroblastoma, B) cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sézary syndrome),
          C) is at high risk for developing skin cancer (squamous cell cancers), D) transient acantholytic dermatosis (Grover’s Disease), E) keratosis follicularis
          (Darier Disease), F) lamellar ichthyosis, G) pityriasis rubra pilaris

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.; April 2022.
2. Accutane [package insert]. Scottsdale, AZ: JG Pharma Inc.; July 2020.
3. Amnesteem [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; January 2022.
4. Claravis [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; January 2022.
5. Myorisan [package insert]. Lake Forest, IL: VersaPharm Inc.; August 2019.
6. Zenatane [package insert]. Princeton, NJ: Dr. Reddy’s Laboratories, Inc.; February 2022.
7. Lexicomp Online, AHFS DI (Adult and Pediatric) Online, Hudson, Ohio: UpToDate, Inc.; 2022; Accessed July 11, 2022.
8. Micromedex (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www.micromedexsolutions.com. Accessed July 11, 2021.
9. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-973.
10. National Institute of Arthritis and Musculoskeletal and Skin Diseases. http://www.niams.nih.gov/Health_Info/Rosacea/default.asp#6. Accessed July 11, 2022.
11. Granulomatous Rosacea. National Center for Advancing Translational Sciences: Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/6548/granulomatous-rosacea. Accessed July 11, 2022.
12. 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, 2014;93:134-38.
13. Neuroblastoma Treatment. National Cancer Institute at the National Institute of Health. https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#_707_toc. Accessed July 11, 2022.
14. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Squamous Cell Skin Cancer. Version 1.2021. NCCN Guidelines Available at: nccn.org. Accessed July 11, 2022.
15. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Primary Cutaneous Lymphomas. Version 2.2021. Available at: www.nccn.org. Accessed July 11, 2022.
16. Office of Rare Disease Research. NIH National Center for Advancing Translational Sciences. Transient acantholytic https://rarediseases.info.nih.gov/gard/6551/transient-acantholytic-dermatosis/resources/8#2884. Accessed July 11, 2022.
17. National Organization for Rare Disorders, Inc. Grover’s Disease. https://rarediseases.org/rare-diseases/grovers-disease. Accessed July 11, 2022.
18. American Osteopathic College of Dermatology. Grover's Disease. http://www.aocd.org/?page=GroversDisease. Accessed July 11, 2022.
19. Darier disease. Office of Rare Disease Research. https://rarediseases.info.nih.gov/gard/6243/darier-disease/resources/8. Accessed July 11, 2022.
20. Darier Disease. American Osteopathic College of Dermatology. http://www.aocd.org/skin/dermatologic_diseases/darier_disease.html. Accessed July 11, 2022.
21. Lamellar ichthyosis. Office of Rare Disease Research. https://rarediseases.info.nih.gov/gard/10803/lamellar-ichthyosis/resources/8. Accessed July 11, 2022.
22. Pityriasis rubra pilaris. Office of Rare Disease Research. https://rarediseases.info.nih.gov/gard/7401/pityriasis-rubra-pilaris/resources/8. Accessed July 11, 2022.
23. Pityriasis Rubra Pilaris. American Osteopathic College of Dermatology. http://www.aocd.org/?page=PityriasisRubraPil. Accessed July 11, 2022.

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 10, 2022