Subject: Actinic Keratosis Products PA 1378-A P07-2025

Drug

Actinic Keratosis Products

CARAC  (fluorouracil)

KLUSYRI  (tirbanibulin)

TOLAK  (fluorouracil)

ZYCLARA  (imiquimod)

Policy:

FDA-approved Indications

Carac

Carac is indicated for the topical treatment of multiple actinic or solar keratoses of the face and anterior scalp.

Klisyri

Klisyri is indicated for the topical field treatment of actinic keratosis on the face or scalp.

Tolak

Tolak (fluorouracil) cream is indicated for the topical treatment of actinic keratosis lesions of the face, ears, and/or scalp.

Zyclara

Actinic Keratosis

Zyclara, 2.5% and 3.75% are indicated for the topical treatment of clinically typical, visible or palpable actinic keratoses (AK) of the face or balding scalp in immunocompetent adults.

External Genital Warts

Zyclara, 3.75% is indicated for the topical treatment of external genital and perianal warts (EGW) in immunocompetent patients 12 years of age and older.

Coverage Criteria

Actinic Keratosis (AK)

Authorization may be granted for the treatment of actinic keratosis (AK) when ONE of the following criteria is met:

• The request is for Carac, Tolak, OR Zyclara.
• The request is for Klisyri AND the following criteria is met:
  • The patient experienced an inadequate treatment response, intolerance, OR has a contraindication to ANY of the following: imiquimod 5 percent cream, fluorouracil cream or solution.

External Genital Warts (EGW)

Authorization may be granted for the treatment of external genital warts (EGW) when the following criteria is met:

• The request is for Zyclara.

Continuation of Therapy

Actinic Keratosis (AK)

Authorization may be granted for the treatment of actinic keratosis (AK) when the following criteria is met:

• The patient has achieved or maintained a positive clinical response as evidenced by improvement (e.g., percentage of actinic keratosis lesions cleared, patient/prescriber satisfaction, etc.).

External Genital Warts (EGW)

Authorization may be granted for the treatment of external genital warts (EGW) when ALL of the following criteria are met:

• The request is for Zyclara.
• The patient has achieved or maintained a positive clinical response as evidenced by improvement (e.g., percentage of warts cleared).

Duration of Approval (DOA)

• 1378-A: Initial therapy DOA: 4 months; Continuation of therapy DOA: 12 months

Place of Service:

Outpatient

The above policy is based on the following references:

1. Carac [package insert]. Bridgewater, NJ: Bausch Health US, LLC; May 2021.
2. Klisyri [package insert]. Malvern, PA: Almirall, LLC; June 2024.
3. Tolak [package insert]. Sanford, FL: Hill Dermaceuticals, Inc.; August 2022.
4. Zyclara [package insert]. Bridgewater, NJ: Bausch Health US, LLC; September 2024.
5. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Waltham, MA: UpToDate, Inc.; 2025. https://online.lexi.com. Accessed May 28, 2025.
6. Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; 2025. https://online.lexi.com. Accessed May 28, 2025.
7. Micromedex® (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com/ (cited: 05/28/2025).
8. Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. J Am Acad 2021;85:e209-e233.
9. Eisen DB, Dellavalle RP, Frazer-Green L, et al. Focused update: Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2022;87:374.e1-374.e5.
10. Steeb T, Wessely A, Petzold A, et al. How to Assess the Efficacy of Interventions for Actinic Keratosis? A Review with a Focus on Long-Term Results. J Clin Med. 2021 Oct 15;10(20):4736.

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.

October 11, 2025