Acne is a skin issue that arises due to a multitude of factors, such as follicular hyperkeratinization, excessive sebum production, a bacterial overgrowth (notably Cutibacterium acnes), and inflammation.The approach to treating acne is largely influenced by its severity. Therapeutic options aim to address the multiple contributing factors of acne pathogenesis.

1. First-line therapy generally includes topical formulations such as benzoyl peroxide or salicylic acid, which function to prevent oil gland obstruction, and topical antibiotics to manage bacterial proliferation.
2. For moderate to severe or refractory acne, systemic treatments may be warranted. Oral antibiotics are utilized for their anti-inflammatory and antibacterial properties. Hormonal therapies, including certain oral contraceptive pills, can be particularly beneficial in female patients, where hormonal fluctuations can exacerbate the condition.
3. For recalcitrant or severe forms of acne, prescription medications such as isotretinoin may be employed. Isotretinoin acts by profoundly reducing sebum production, thus targeting a key component of acne pathogenesis.
4. Additional treatment options may include light or laser therapies and chemical peels, which help reduce bacteria and inflammation, and remove dead skin cells. For severe or hard-to-treat acne, more intense methods like injections or surgery can be used, but these are usually aimed at dealing with leftover acne scars rather than treating current acne outbreaks.

Isotretinoin, a retinoid medication, is often prescribed for severe acne when other treatments have proven ineffective. It carries serious risks, and to ensure safe use, the iPLEDGE program is in place, and has specific registration and requirements for:

• Wholesalers/distributors
• Prescribers
• Pharmacies
• Patients (members)

The iPLEDGE program can be accessed at https://www.iPledgeprogram.com or by calling 1-866-495-0654.

Table 1: Oral Retinoids for Acne

Drugs that the FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products, i.e., drugs products for which there are no known or suspected bioequivalence problems, and can be substituted for one another (e.g., AB1 can be substituted with AB1 products, but not AB2). #NR (Not Rated), Products listed in the Orange Book that are not multi-source (i.e., no FDA-approved generic equivalents).

Definitions

Acanthosis Nigricans

a skin condition characterized by dark, thick, velvety skin in body folds and creases.creases.

Acne

a type of skin problem, more commonly known as pimples.

Carcinoma

another word for cancer.

Neoplasm

a word commonly used to describe fast and abnormal growth of tissues due to cells dividing too fast.

Neuroblastoma

a type of cancer that starts in early forms of nerve cells found in an embryo or fetus.

Psoriasis

a chronic skin condition that speeds up the life cycle of skin cells causing cells to build up rapidly on the surface of the skin.

Recalcitrant

means hard to deal with or treat.

Rosacea

a type of skin problem that affects areas of the skin such as face, cheeks, nose, forehead and chin–causing redness or raised bumps.

Squamous Cell Carcinoma

a type of skin cancer that begins in the squamous cells.

Medical Necessity Criteria for Authorization

The Plan considers isotretinoin medically necessary when ONE of the following criteria is met:

1. The member meets BOTH of the following criteria:

a.

Medical Necessity Criteria for Authorization

The Plan considers isotretinoin medically necessary when ONE of the following criteria is met:

1. The member has ONE of the following diagnoses:
   1. severe recalcitrant nodular (cystic) acne; or
   2. severe refractory rosacea; or
   3. moderate to severe acne vulgaris; and
2. The member is unable to use, or has tried and failed BOTH of the following conventional therapies:
   1. topical agent (e.g., clindamycin phosphate, benzoyl peroxide); and
   2. oral antibiotics (e.g., doxycycline); OR
3. The medication is being requested for ONE of the following diagnoses or uses:
   • acanthosis nigricans; or
   • advanced squamous cell carcinoma of the skin, refractory to standard therapy; or
   • cutaneous T-cell lymphoma (including mycosis fungoides and Sézary syndrome); or
   • high-risk neuroblastoma; or
   • keratoacanthomas; or
   • keratosis follicularis (Darier’s disease); or
   • keratosis palmaris et plantaris; or
   • lamellar ichthyosis; or
   • pityriasis rubra pilaris (PRP); or
   • prevention of squamous cell skin cancer for a member with high-risk; or
   • psoriasis, severe or pustular; or
   • squamous cell carcinoma of the lung, with inoperable neoplasms.
   If the above prior authorization criteria are met, isotretinoin will be approved for 12 months.

Experimental or Investigational / Not Medically Necessary

Isotretinoin for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

References

1. Absorica/Absorica LD (isotretinoin) [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries Inc; December 2021.
2. Accutane (isotretinoin) [prescribing information]. Scottsdale, AZ: JG Pharma, Inc; July 2020.
3. Accutane Roche (isotretinoin) [prescribing information]. Mississauga, Ontario, Canada: Hoffmann-La Roche Limited; August 2019.
4. American Academy of Dermatology website. Position statement on isotretinoin. https://www.aad.org/Forms/Policies/Uploads/PS/PS-lsotretinoin.pdf. Accessed May 2022. https://www.aad.org/Forms/Policies/Uploads/PS/PS-Isotretinoin.pdf. Accessed May 2022.
5. Amnesteem (isotretinoin) [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals Inc; January 2022.
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8. Bienenfeld A et al: Androgens in women: androgen-mediated skin disease and patient evaluation. J Am Acad Dermatol. 80(6):1497-506, 2019
9. Bolognia, J. L., Schaffer, J. V., Cerroni, L., & Callen, J. P. (2018). Dermatology. Elsevier.
10. Claravis (isotretinoin) [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA Inc; January 2022.
11. Collier CN et al: The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 58(1):56-9, 2008
12. Dall'Oglio F et al: Diet and acne: review of the evidence from 2009 to 2020. Int J Dermatol. 60(6):672-85, 2021
13. Eichenfield DZ et al: Management of acne vulgaris: a review. JAMA. 326(20):2055-67, 2021
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16. Fallah H et al: Isotretinoin in the management of acne vulgaris: practical prescribing. Int J Dermatol. 60(4):451-60, 2021
17. Greywal T et al: Evidence-based recommendations for the management of acne fulminans and its variants. J Am Acad Dermatol. 77(1):109-17, 2017
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2. Marson JW et al: An overview of acne therapy, part 2: hormonal therapy and isotretinoin. Dermatol Clin. 37(2):195-203, 2019
3. Moore AY et al: Sarecycline: a review of preclinical and clinical evidence. Clin Cosmet Investig Dermatol. 13:553-60, 2020
4. Myorisan (isotretinoin) [prescribing information]. Lake Forest, IL: VersaPharm Inc; August 2019.
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13. Vallerand IA, Lewinson RT, Farris MS, et al. Efficacy and adverse events of oral isotretinoin for acne: a systematic review. Br J Dermatol. 2018;178(1):76-85. doi:10.1111/bjd.15668
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Clinical Guideline Revision / History Information

Original Date: 06/23/2022

Reviewed/Revised: 06/29/2023