ModifiedPremera BluecrossPolicy N/A

Topical pharmacologic treatment of actinic keratosis

Defines medical necessity criteria and documentation for topical prescription drugs used to treat actinic keratosis (AK) and some external genital/perianal wart (EGW) indications; applies to pharmacy benefit management for covered individuals/providers.

Policy Summary

PayerPremera Bluecross

PolicyTopical pharmacologic treatment of actinic keratosis

Policy CodePolicy N/A

Change TypeMaterial updates and product removals

Effective DateMar. 1, 2025

Next Review DateN/A

Key ActionPrior to approval of branded topical agents, document trial and inadequate response or intolerance to generic imiquimod 5% and one generic topical fluorouracil (unless contraindicated).

SourceLink

POLICY UPDATE CHANGES

Removed Aldara (imiquimod 5%) and brand imiquimod 3.75% from policy as the products have been discontinued and are no longer commercially available.

Added coverage criteria for generic imiquimod 3.75% for the treatment of actinic keratosis and external genital and perianal warts (EGW).

Removed Fluoroplex and Solaraze as products have been discontinued by the manufacturer.

Clarified that non-formulary exception review authorizations for all drugs listed in this policy may be approved for up to 12 months.

Clarified that the medications listed in this policy are subject to the product's FDA dosage and administration prescribing information.

Adults 18+Minimum age stated for most AK topical approvals

Up to 12 monthsMax authorization duration

5 daysKlisyri application duration

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Approximate cure rate cited

2025-03-01Most recent review date

multipleTopical products referenced

Coverage Criteria

Generic imiquimod 5% and generic topical fluorouracil required prior to listed branded/topical agents

Covered when ALL of the following are met for specified topical agents:

Age requirement: Individual is aged 18 years or older (unless a different age is specified elsewhere).>=18 years

based on FDA labeling

First-line imiquimod trial: Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5%, unless use is contraindicated.trial and inadequate response or intolerance

step therapy requirement

Topical fluorouracil trial: Has tried one generic topical fluorouracil product first and had an inadequate response or intolerance to topical fluorouracil.trial and inadequate response or intolerance

step therapy requirement

Agent-specific criteria

Agent-specific medical necessity examples (policy lists multiple agents with same core criteria):

Carac (fluorouracil 0.5%): Carac may be considered medically necessary for the topical treatment of actinic keratosis in adults when the general step therapy and age criteria are met.

Brand fluorouracil may be considered medically necessary for the topical treatment of actinic keratosis in adults when the general step therapy and age criteria are met.

Imiquimod 3.75% (generic): Generic imiquimod 3.75% may be considered medically necessary for the topical treatment of actinic keratosis in adults when the age and prior trial criteria are met; generic imiquimod 3.75% may also be considered medically necessary for external genital and perianal warts (EGW) when the EGW-specific age and prior trial criteria are met.

EGW age criterion differs (see node)

Klisyri (tirbanibulin): Klisyri may be considered medically necessary for the topical treatment of actinic keratosis in adults when the general step therapy and age criteria are met.

All uses of the drugs that are not specifically outlined in this policy are considered investigational. The medications listed within this policy are subject to the product's US Food and Drug Administration (FDA) dosage and administration prescribing information. Non-formulary exception reviews and other initial or re-authorization reviews for drugs in this policy may be approved for up to 12 months when the drug-specific coverage criteria are met and chart notes document clinical response.

This medical policy is a guide to evaluate medical necessity for specified topical products; however, it does not apply to Medicare Advantage. Coverage remains subject to the limits and conditions of the member's benefit plan, and providers should verify benefits with the member's contract or customer service prior to submitting requests.

Indications that are not specifically listed in this policy are considered investigational (not medically necessary). Requests for uses outside the stated indications are not supported by this policy and will be managed accordingly; providers should follow FDA prescribing information and submit supporting documentation if requesting exception coverage.

Coding

Codingmixed

No codes listed

Provider Actions & Authorization Rules

Prior Authorization

Prior authorization duration and general rule

Prior authorization is required for non-formulary exception reviews for drugs listed in this policy. Non-formulary exception reviews may be approved for up to 12 months when criteria are met.

Non-formulary exception approvals: up to 12 months
All other reviews/authorizations: may be approved up to 12 months

Note

Policy changes and prior authorization note

Policy coverage changes (additions/removals) affect coverage and prior authorization processes. Removed products that are discontinued are not covered and should not be requested. Verify that requested products remain commercially available.

Removed from policy and not commercially available: Aldara (imiquimod 5%), brand imiquimod 3.75%
Added: generic imiquimod 3.75% coverage criteria for actinic keratosis and EGW

Background

Actinic keratoses (AK) are common, rough, scaly lesions that develop on chronically sun-exposed skin (for example the face, scalp, neck, hands, and forearms) and are considered precancerous. A subset of AK lesions can progress to squamous cell carcinoma, so treatment selection considers lesion count, anatomic location, and risk of progression. For isolated lesions, destructive approaches such as cryotherapy are commonly used, whereas topical field therapies and photodynamic therapy are used for multiple or field lesions. Management and coverage decisions should align with guideline recommendations and the FDA-approved dosing and administration for the prescribed topical agent.

Definitions

Actinic keratosis (AK) definition and clinical features

DefinitionActinic keratosis (AK): rough, scaly patches or crusty bumps on sun‑exposed skin (face, scalp, neck, ears, lips, back of hands, forearms) that are considered precancerous and may progress to squamous cell carcinoma.

Clinical presentationLesions are often more easily felt than seen, may be itchy or painful, and commonly occur on chronically UV‑exposed sites.

Risk of progressionAn estimated 5–20% of AK lesions may transform to squamous cell carcinoma over 10–25 years; reported annual transformation rates range from 0.25% to 16%.

Epidemiology/impactApproximately 4 million individuals are treated annually in the US; at least one AK lesion will develop over a lifetime in about 1 in 6 persons.

Treatment considerationsTreatment choice depends on number and location of lesions: cryotherapy for few lesions; topical therapies and photodynamic therapy for field treatment or numerous lesions.

Policy Summary

PayerPremera Bluecross

PolicyTopical pharmacologic treatment of actinic keratosis

Policy CodePolicy N/A

Change TypeMaterial updates and product removals

Effective DateMar. 1, 2025

Next Review DateN/A

Key ActionPrior to approval of branded topical agents, document trial and inadequate response or intolerance to generic imiquimod 5% and one generic topical fluorouracil (unless contraindicated).

SourceLink

On This Page

Tolak (fluorouracil 4%): Tolak may be considered medically necessary for the topical treatment of actinic keratosis in adults when the general step therapy and age criteria are met.

Zyclara (imiquimod 2.5% and 3.75%): Zyclara may be considered medically necessary for the topical treatment of actinic keratosis in adults when the general step therapy and age criteria are met; Zyclara 3.75% may be considered medically necessary for EGW in individuals aged 12 years and older when the required trial of generic imiquimod 5% and intolerance criteria are met.

EGW age >=12 years per policy

Step Therapy

Required prior trials (step therapy)

Step therapy is required. Prior to approval of branded agents or non-preferred products, the individual must have tried and had an inadequate response or intolerance to first-line generics unless contraindicated.

Required trials: generic imiquimod 5% AND one generic topical fluorouracil product
If contraindicated or intolerant to the required agents, document rationale in chart notes

Note

Provider submission requirements

Provider action placeholder — ensure prior authorization requests include the documentation listed below and any policy-specific evidence of prior trials or contraindications.

Include specific drug name, dates of trial, response or adverse effects, and reason for switching
Confirm product availability before submission

Documentation Required

Required documentation

Medical record documentation must be submitted to support medical necessity. Records should include diagnosis, relevant history, physical evaluation, and medication history demonstrating required prior trials or contraindications.

Office visit notes with diagnosis and assessment
Medication history showing dates and outcomes of trials of generic imiquimod 5% and a generic topical fluorouracil
Documentation of intolerance or contraindication when applicable

Documentation Required

Documentation and exception duration

Non-formulary exception review authorizations may be approved up to 12 months. All medications listed are subject to FDA prescribing information; chart notes must demonstrate continued clinical benefit for re-authorization.

Initial non-formulary exception: up to 12 months
Re-authorization: up to 12 months if continued positive clinical response is documented
All use must follow FDA dosage and administration

Denial Risk

Failure to meet step therapy requirements

Requests for branded agents without documented trials of required first-line generics or without documented contraindication/intolerance are at high risk of denial.

Denial risk when step therapy requirements are not met
Include explicit documentation if requesting bypass of step therapy

Note

Benefit verification required

Coverage is subject to the member's benefit plan limits. Always verify member benefits and eligibility prior to submitting authorization requests.

Confirm member benefits and any plan exclusions or limits
Contact member services for benefit-specific questions

Actinic keratosis guidelines referenced

British Journal of Dermatology (2017)Guidelines for the Care of Patients with Actinic Keratosis (Berker et al., Br J Dermatol 2017).

American Academy of Dermatology (2021)Guidelines of care for the management of actinic keratosis (Eisen et al., Am Acad Dermatol 2021).

AAD focused update (2022)Focused update: Guidelines of care for the management of actinic keratosis (J Am Acad Dermatol 2022).

Policy references include topical agent prescribing infoPolicy references prescribing information for topical agents (e.g., Carac, Klisyri, Tolak, Zyclara) as sources for drug‑specific details.