CurrentPremera BluecrossPolicy 5.01.623

PHARMACY POLICY -5.01.623 Dermatologic Conditions

This pharmacy policy defines medical necessity criteria for specific topical prescription drugs (e.g., Carac, brand and generic fluorouracil, imiquimod formulations, Klisyri, Tolak, Zyclara) used to treat actinic keratosis in adults and select indications (external genital and perianal warts for some agents); it governs pharmacy benefit coverage, length of approval, re-authorization, and documentation requirements.

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY POLICY -5.01.623 Dermatologic Conditions

Policy CodePolicy 5.01.623

Change TypeAnnual review; formulary updates (2025)

Effective DateJun 1, 2026

Next Review Date

Key ActionInitial authorization for all drugs listed may be approved up to 12 months; re-authorization may be approved up to 12 months if drug-specific criteria are met and chart notes document continued positive clinical response.

SourceLink

POLICY UPDATE CHANGES

06/01/26 annual review: prescribing information reviewed; policy statements unchanged.

03/01/25 annual review: removed Aldara (imiquimod 5%) and brand imiquimod 3.75% due to discontinuation; added generic imiquimod 3.75% coverage for AK and EGW; clarified FDA dosing language and non-formulary exception duration.

2022-2024 updates: prescribing information reviewed; removed discontinued products Solaraze and Fluoroplex in earlier updates; no policy statement changes in 2022-2024.

MultipleCovered topical products (examples)

12 monthsMax initial/re-authorization approval

≥18

Adult age requirement

≥12Pediatric age exception for EGW

Coverage Summary

This pharmacy policy defines medical necessity criteria for specific topical prescription drugs used to treat actinic keratosis (AK) in adults and select related indications (for example, external genital and perianal warts [EGW] for some agents). Covered topical products include multiple agents such as Carac (fluorouracil 0.5%), brand and generic fluorouracil formulations, imiquimod formulations (including generic imiquimod 3.75% and generic imiquimod 5%), Klisyri (tirbanibulin), Tolak (fluorouracil 4%), and Zyclara. The policy governs pharmacy benefit coverage, required documentation, and length of approval.

Key facts

Covered topical products (examples)Multiple topical agents (e.g., fluorouracil formulations, imiquimod formulations, tirbanibulin, diclofenac)

Max initial/re-authorization approvalInitial authorization up to 12 months; re-authorization may be approved up to 12 months if criteria met and chart notes document continued positive clinical response

Adult age requirementAge ≥18 for most indications and listed topical drugs

Pediatric age exception for EGWAge ≥12 for imiquimod 3.75% (treatment of external genital and perianal warts)

Initial Therapy Criteria

Carac (fluorouracil 0.5%) - Medical Necessity

Carac (fluorouracil 0.5%) may be considered medically necessary when ALL of the following are met:

ALL of the following

Individual is aged 18 years and older
Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5% unless use is contraindicated
Has tried 1 generic topical fluorouracil product first and had an inadequate response or intolerance to topical fluorouracil

Brand fluorouracil (topical) - Medical Necessity

Brand fluorouracil may be considered medically necessary when ALL of the following are met:

ALL of the following

External Genital & Perianal Warts (EGW) Criteria

Generic imiquimod 3.75% - Medical Necessity for EGW

Generic imiquimod 3.75% may be considered medically necessary for treatment of external genital and perianal warts when ALL of the following are met (pediatric exception: age ≥12):

ALL of the following

Individual is aged 12 years and older
Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5%

Zyclara (imiquimod 3.75%) - Medical Necessity for EGW

Zyclara (imiquimod 3.75%) may be considered medically necessary for treatment of external genital and perianal warts when ALL of the following are met (pediatric exception: age ≥12):

ALL of the following

Continuation Therapy & Investigational Uses

Initial authorization for all drugs listed in the policy may be approved for up to 12 months. Re-authorization may be approved for up to 12 months provided the drug-specific coverage criteria are met and chart notes document that the individual continues to show a positive clinical response to therapy; medical records must document diagnosis, relevant history, physical evaluation, medication history, and evidence that policy medical necessity criteria are met.

Investigational / Not Covered

All other uses of the drugs listed in this policy for conditions not outlined in this policy are considered investigational.

All other uses of the drugs listed in this policy for conditions not outlined in this policy are considered investigational

Provider Actions & Authorization

Prior Authorization

Prior authorization / Length of approval

Initial authorization for all drugs listed may be approved up to 12 months; re-authorization may be approved up to 12 months if drug-specific criteria are met and chart notes document continued positive clinical response.

Documentation Required

Required medical record documentation

Medical records must document diagnosis, relevant history, physical evaluation, medication history, and evidence that policy medical necessity criteria are met (e.g., prior trial and intolerance or inadequate response to specified agents).

Applicable Codes

Codingmixed

No codes listed

Clinical Evidence Summary

~75%Topical 5‑FU cure rate (2–4 weeks)

Evidence shows variable efficacy among topical AK treatments: tirbanibulin achieved complete clearance rates of 44% and 54% at Day 57 in two trials of face/scalp lesions (4–8 lesions per 25 cm2); topical imiquimod 5% demonstrated complete clearance of approximately 44–46% versus low vehicle rates in trials; and topical fluorouracil (5-FU) has historically been considered the standard with cure rates around ~75% for typical 2–4 week regimens. Treatment selection varies by lesion count, anatomic location, and severity.

Background

Actinic keratosis (AK) are precancerous, sun-induced rough, scaly patches on sun-exposed skin that can progress to squamous cell carcinoma; they commonly occur on the face, scalp, neck, lips, and hands. Treatment options include procedural approaches (e.g., cryotherapy, curettage), photodynamic therapy, and topical drugs. Choice of therapy depends on lesion count, location, and severity: cryotherapy is typically used for isolated lesions, whereas topical therapies (and PDT) are commonly used for field disease or when many lesions are present. Definitions: AK = actinic keratosis, precancerous skin lesions due to UV exposure; EGW = external genital and perianal warts.

Revision History

06/01/26annual_reviewLatest

annual review: prescribing information reviewed; policy statements unchanged.

03/01/25annual_review

annual review: removed Aldara (imiquimod 5%) and brand imiquimod 3.75% due to discontinuation; added coverage criteria for generic imiquimod 3.75% for actinic keratosis and external genital/perianal warts; clarified FDA dosing language and that non-formulary exception review authorizations may be approved up to 12 months.

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY POLICY -5.01.623 Dermatologic Conditions

Policy CodePolicy 5.01.623

Change TypeAnnual review; formulary updates (2025)

Effective DateJun 1, 2026

Next Review Date

SourceLink

On This Page

Individual is aged 18 years and older
Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5% unless use is contraindicated
Has tried 1 generic topical fluorouracil product first and had an inadequate response or intolerance to topical fluorouracil

Generic imiquimod 3.75% - Medical Necessity for AK

Generic imiquimod 3.75% may be considered medically necessary for topical treatment of actinic keratosis when ALL of the following are met:

ALL of the following

Individual is aged 18 years and older
Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5%
Has tried 1 generic topical fluorouracil product first and had an inadequate response or intolerance to topical fluorouracil unless use is contraindicated

Klisyri (tirbanibulin) - Medical Necessity

Klisyri (tirbanibulin) may be considered medically necessary when ALL of the following are met:

ALL of the following

Individual is aged 18 years and older
Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5% unless use is contraindicated
Has tried 1 generic topical fluorouracil product first and had an inadequate response or intolerance to topical fluorouracil

Tolak (fluorouracil 4%) - Medical Necessity

Tolak (fluorouracil 4%) may be considered medically necessary when ALL of the following are met:

ALL of the following

Individual is aged 18 years and older
Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5% unless use is contraindicated
Has tried 1 generic topical fluorouracil product first and had an inadequate response or intolerance to topical fluorouracil

Zyclara (imiquimod 2.5% and 3.75%) - Medical Necessity for AK

Zyclara (imiquimod 2.5% and 3.75%) may be considered medically necessary for topical treatment of actinic keratosis when ALL of the following are met:

ALL of the following

Individual is aged 18 years and older
Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5%
Has tried 1 generic topical fluorouracil product first and had an inadequate response or intolerance to topical fluorouracil unless use is contraindicated

Individual is aged 12 years and older

Has tried generic imiquimod 5% first and had an inadequate response or intolerance to generic imiquimod 5%

Denial Risk

Investigational use denial

Claims for uses not specified in this policy are considered investigational and subject to denial.