CurrentBlue Cross Blue Shield - IowaPolicy 05.01.35

Keratolytics and Other Dermatologic Agents (topical agents for actinic keratosis, external genital and perianal warts)

Defines medical necessity and prior authorization requirements for branded and generic topical agents used to treat actinic keratosis, external genital warts, and perianal warts for Wellmark Blue Cross and Blue Shield members.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyKeratolytics and Other Dermatologic Agents (topical agents for actinic keratosis, external genital and perianal warts)

Policy CodePolicy 05.01.35

Change TypeNo material clinical or coverage changes

Effective DateNov 17, 2021

Next Review DateAug 1, 2025

Key ActionObtain prior authorization and document diagnosis, age, prior therapies (including cryotherapy) and reasons for contraindication or adverse events.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Severalagents covered

12 / 18+age rules

1–6 monthsauthorization periods

5 packets/25dKlisyrie limit

Coverage Criteria for Topical Dermatologic Agents

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Carac (fluorouracil 0.5% cream) — Actinic Keratosis

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

Carac AK criteria: Patient has a diagnosis of actinic keratosis; patient is 18 years of age or older; patient has tried and failed cryotherapy unless otherwise contraindicated; patient has tried and failed OR had an adverse event OR has a contraindication to topical fluorouracil solution or the generic 5% cream unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 3 months

Zyclara (imiquimod 2.5% and 3.75%) — Actinic Keratosis

Zyclara (imiquimod 2.5% and 3.75%) brand and generic may be considered medically necessary when ALL of the following are met:

Zyclara AK criteria: Patient has a diagnosis of AK; patient is 18 years of age or older; patient has tried and failed cryotherapy unless otherwise contraindicated; patient has tried and failed OR had an adverse event OR has a contraindication to imiquimod 5% unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded); patient has tried and failed OR had an adverse event OR has a contraindication to topical fluorouracil solution or the generic 5% cream unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 3 months

Zyclara (imiquimod 3.75%) — External Genital Warts (EGW)

Zyclara 3.75% may be considered medically necessary for external genital warts (EGW) when ALL of the following are met:

Zyclara EGW criteria: Patient has a diagnosis of external genital warts; patient is 12 years of age or older; requested strength is indicated for EGW treatment (3.75%); patient has tried and failed OR had an adverse event OR has a contraindication to podofilox solution unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded); patient has tried and failed cryotherapy unless otherwise contraindicated; patient has tried and failed OR had an adverse event OR has a contraindication to imiquimod 5% unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 3 months

Zyclara (imiquimod 3.75%) — Perianal Warts

Zyclara 3.75% may be considered medically necessary for perianal warts when ALL of the following are met:

Zyclara perianal criteria: Patient has a diagnosis of perianal warts; patient is 12 years of age or older; requested strength is indicated for perianal warts (3.75%); patient has tried and failed OR had an adverse event OR has a contraindication to imiquimod 5% unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded); patient has tried and failed cryotherapy unless otherwise contraindicated.

Approval period: 3 months

Klisyrie (tirbanibulin 1% ointment) — Actinic Keratosis

Klisyrie (tirbanibulin 1% ointment) may be considered medically necessary when ALL of the following are met:

Klisyrie AK criteria: Documented diagnosis of actinic keratosis of the face or scalp; patient is 18 years of age or older; patient has tried and failed cryotherapy unless otherwise contraindicated; patient has tried and failed OR had an adverse event OR has a contraindication to topical fluorouracil solution or the generic 5% cream unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded); patient has a contraindication to imiquimod 5% unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 1 month; quantity limit: one box of 5 single-use packets per 25 days

Condylox (podofilox) gel — External genital (anogenital) warts

Condylox (podofilox) gel may be considered medically necessary for external genital (anogenital) warts when ALL of the following are met:

Condylox gel EGW criteria: Documented diagnosis of external genital warts; patient is 18 years of age or older; patient has tried and failed cryotherapy unless otherwise contraindicated; patient has tried and failed OR had an adverse event OR has a contraindication to podofilox solution unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 3 months

Condylox gel — Perianal warts

Condylox gel may be considered medically necessary for perianal warts when ALL of the following are met:

Condylox gel perianal criteria: Documented diagnosis of perianal warts; patient is 18 years of age or older; patient has tried and failed cryotherapy unless otherwise contraindicated; patient has tried and failed OR had an adverse event OR has a contraindication to imiquimod 5% unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 3 months

Veregen (sinecatechins) ointment — External genital and perianal warts

Veregen (sinecatechins) ointment may be considered medically necessary when ALL of the following are met:

Veregen EGW criteria: Patient is 18 years of age or older; patient has tried and failed cryotherapy unless otherwise contraindicated; patient has a documented diagnosis of external genital warts; patient has tried and failed OR had an adverse event OR has a contraindication to podofilox solution unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 1 month for external genital warts

Veregen perianal criteria: Patient has a documented diagnosis of perianal warts; patient is 18 years of age or older; patient has tried and failed cryotherapy unless otherwise contraindicated; patient has tried and failed OR had an adverse event OR has a contraindication to imiquimod 5% unless the patient is currently receiving a positive therapeutic outcome on the requested medication through health insurance (samples/PAP excluded).

Approval period: 6 months

When a requested topical agent is submitted for coverage, the medication will be deemed not medically necessary if the patient does not meet the specific, medication‑level criteria listed in this policy. Key elements that must be documented and satisfied include the appropriate diagnosis (actinic keratosis, external genital warts, or perianal warts), the minimum age required for that agent, and completion of required step therapy such as a trial of cryotherapy unless contraindicated. Requests lacking documentation of these criteria, evidence of required prior trials or documented contraindications/adverse events, or other medication‑specific requirements will be denied as not medically necessary.

The following agents are considered not medically necessary for patients who do not meet the criteria set forth for each medication: Carac (fluorouracil 0.5% cream), Zyclara (imiquimod 2.5% and 3.75%), Klisyrie (tirbanibulin 1% ointment), Condylox (podofilox) gel, and Veregen (sinecatechins) ointment. For each agent, coverage requires meeting the agent‑specific elements in this policy (diagnosis, age requirement, trials of cryotherapy and specified topical alternatives or documented contraindications/adverse events). Requests for these agents that do not meet those medication‑specific criteria will be denied as not medically necessary.

Prior Authorization, Step Therapy, and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for certain branded and some generic topical agents; approvals are granted only when the listed clinical criteria are met.

Affected products include Carac (fluorouracil 0.5%), Zyclara (2.5% and 3.75%), Klisyri (1%), Condyloxe gel, Veregene ointment, and certain generics/brands for AK, external genital warts (EGW), and perianal warts.

Step Therapy

Step Therapy / Therapeutic Trial Requirements

Step therapy must be demonstrated prior to approval for many topical treatments. Providers should document trials, failures, adverse events, or contraindications as specified below.

A trial and failure of cryotherapy is required for AK, EGW, and perianal wart indications unless cryotherapy is contraindicated.
For Carac, Zyclara, Klisyri and other AK agents: the patient must have tried and failed OR had an adverse event OR have a contraindication to alternative topical therapies (e.g., topical fluorouracil solutions, fluorouracil 5% cream, or imiquimod 5%) prior to approval.
For EGW and perianal warts: the patient must have tried and failed OR had an adverse event OR have a contraindication to podofilox solution and to imiquimod 5% (when applicable) prior to approval.

Documentation Required

Required Clinical Documentation

Complete clinical documentation is required to support requests and avoid denial.

Diagnosis and anatomic location (AK, EGW, perianal warts)
Patient age (must meet age thresholds per product: AK agents generally ≥18 years; Zyclara/Klisyri for EGW/perianal warts may be ≥12 years where specified)
Documentation of prior cryotherapy trial and outcome or reason for contraindication
Documentation of trials, failures, adverse events, or contraindications to listed alternate topical therapies (e.g., fluorouracil 5% or solution, imiquimod 5%, podofilox) — include dates, durations, and clinical response
Current treatment response if patient is already receiving the requested medication (samples or manufacturer assistance program use does not substitute)

Denial Risk

Denial Risk — Carac (fluorouracil 0.5%)

Requests for Carac (fluorouracil 0.5%) that do not include the required step-therapy or contraindication documentation are at high risk of denial.

Ensure documentation of: diagnosis of AK, age ≥18, prior cryotherapy trial (or contraindication), and trial/failure or adverse event/contraindication to topical fluorouracil solution or fluorouracil 5% cream (or documentation that patient is currently benefiting from an alternative covered medication).

Denial Risk

Denial Risk — Zyclara

Requests for Zyclara (2.5% or 3.75%) for EGW or perianal warts that lack the required age, diagnosis, or prior-therapy documentation are at high risk of denial.

Ensure documentation of: diagnosis (EGW or perianal warts), appropriate age (≥12 years for EGW/perianal where specified), strength indication (3.75% where required), prior cryotherapy trial (or contraindication), and trial/failure or adverse event/contraindication to podofilox and imiquimod 5% (or documentation that the patient is currently receiving a positive therapeutic outcome on the requested medication).

OpenPayer

Keratolytics and Other Dermatologic Agents (topical agents for actinic keratosis, external genital and perianal warts)

Coverage Criteria for Topical Dermatologic Agents

Procedures, Billing Codes, and Quantity Limits

Prior Authorization, Step Therapy, and Documentation Requirements

Background and Scope

Key Definitions