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ph-91037

Topical Actinic Keratosis, Basal Cell Carcinoma, Genital Warts Agents Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-91037

The prior authorization with quantity limit program applies to Blue Partner, Commercial, GenPlus, SourceRx, SourceRx-Performance, and Health Insurance Marketplace formularies.

The quantity limit program applies to NetResults A series formulary.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
01-01-2026

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Aldara® (imiquimod) 5% Cream*	Topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses (AK) on the face or scalp in immunocompetent adults Topical treatment of biopsy-confirmed primary superficial basal cell carcinoma (sBCC) in immunocompetent adults, with a maximum tumor diameter of 2.0 cm, located on the trunk (excluding anogenital skin), neck, or extremities (excluding hands and feet), only when surgical methods are medically less appropriate and patient follow-up can be reasonably assured Treatment of external genital and perianal warts (EGW)/condyloma acuminata in patients 12 years or older	*generic available	6
Carac® (fluorouracil) 0.5% Cream*	Topical treatment of multiple actinic or solar keratoses of the face and anterior scalp	*generic available	2
diclofenac 3% Gel	Topical treatment of actinic keratosis (AK)		1
Efudex® (fluorouracil) 5% Cream*	Topical treatment of multiple actinic or solar keratoses (AK) Treatment of superficial basal cell carcinomas (sBCC) when conventional methods are impractical, such as with multiple lesions or difficult treatment sites	*generic available	4
Klisyri® (tirbanibulin) 1% Ointment	Topical treatment of actinic keratosis on the face or scalp		8
Tolak® (fluorouracil) 4% Cream	Topical treatment of actinic keratosis lesions of the face, ears, and/or scalp		5
Zyclara® (imiquimod) 3.75% Cream*	Topical treatment of clinically typical, visible, or palpable actinic keratoses (AK) of the face or balding scalp in immunocompetent adults Treatment of external genital and perianal warts (EGW)/condyloma acuminata in immunocompetent patients 12 years of age or older	*generic available	7
Zyclara® (imiquimod) 2.5% Cream	Topical treatment of clinically typical, visible, or palpable actinic keratoses (AK) of the face or balding scalp in immunocompetent adults		7

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Actinic Keratosis (AK)	Actinic keratoses (AK or solar keratoses) are keratotic or scaling macules, papules, or plaques resulting from the intraepidermal proliferation of atypical keratinocytes in response to prolonged exposure to ultraviolet radiation.(9) Although most AKs do not progress to squamous cell carcinoma (SCC), AKs are a concern because the majority of cutaneous SCCs arise from pre-existing AKs and AKs that will progress to SCC cannot be distinguished from AKs that will spontaneously resolve or persist.(9,10) According to National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD) guidelines, topical first-line therapies for AK include 5-fluorouracil (5-FU), imiquimod, and tirbanibulin.(10,15) Topical diclofenac is considered 2B (based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate) due to varying efficacy results across large randomized trials.(10)
Superficial Basal Cell Carcinoma (BCC)	Basal cell carcinoma (BCC) is a common skin cancer that arises from the basal layer of epidermis and its appendages. Although rarely metastatic, BCC can produce substantial local destruction along with disfigurement and may involve extensive areas of soft tissue, cartilage, and bone. First-line therapy is surgical excision, however for some patients with low-risk superficial BCC, where surgery is contraindicated or impractical, topical therapies such as 5-fluorouracil (5-FU) or imiquimod may be considered, even though the cure rates are nearly 10% lower than surgical excision modalities.(12)
Genital Warts	Condylomomata acuminata, also known as anogenital warts or external genital / perianal warts (EGW), are a manifestation of anogenital human papillomavirus (HPV) infection. The treatment of genital warts should be guided by the extent of disease (e.g., wart size, number, and anatomic site), patient preference, cost and availability of treatment, and the experience of the health care provider. Patient-applied therapies include imiquimod 3.75% or 5%, and Podofilox (podophyllotoxin). The majority of genital warts respond within 3 months of therapy.(14)
Safety	Diclofenac 3% gel has the following box warnings:(1) Cardiovascular risk NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. NSAIDs are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Gastrointestinal risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. Diclofenac 3% gel is contraindicated in patients:(1) With a known hypersensitivity to diclofenac or any components of the drug product With a history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs For use on damaged skin In the setting of coronary artery bypass graft (CABG) surgery Carac, Efudex and Tolak are contraindicated in patients:(2,4-5) Who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus Who have dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. A large percentage of fluorouracil is catabolized by the DPD enzyme. DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities With a known hypersensitivity to any of its components Aldara, Zyclara and Klisyri have no FDA labeled contraindications for use.(6-8)

REFERENCES

Number	Reference
1	Diclofenac 3% gel prescribing information. Glenmark Pharmaceuticals Inc. January 2025.
2	Carac 0.5% cream prescribing information. Bausch Health US, LLC. May 2022.
3	Reference no longer used.
4	Efudex prescribing information. Bausch Health Companies Inc. March 2024.
5	Tolak prescribing information. Hill Dermaceuticals, Inc. August 2022.
6	Aldara prescribing information. Bausch Health US, LLC. September 2024.
7	Zyclara prescribing information. Bausch Health US, LLC. September 2024.
8	Klisyri prescribing information. Almirall, LLC. June 2024.
9	Criscione VD, Weinstock MA, et al. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer 2009; 115:2523.
10	National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Squamous Cell Skin Cancer. Version 2.2025.
11	Reference no longer used.
12	National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. Version 2.2025.
13	Reference no longer used.
14	Workowski KA, Bachmann LH, Chan PA, et al. Centers for Disease Control and Prevention (CDC) Treatment Guidelines on Sexually Transmitted Diseases. MMWR. 2021;70(4):1-187.
15	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(2). doi:10.1016/j.jaad.2022.04.013

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

		5 %	M ; N ; O	Y
	diclofenac sodium (actinic keratoses) gel	3 %	M ; N ; O ; Y	Y
Carac ; Fluorouracil	Fluorouracil Cream 0.5%	0.5 %	M ; N ; O ; Y	M ; N
Tolak	Fluorouracil Cream 4%	4 %	M ; N ; O ; Y	N
Efudex	Fluorouracil Cream 5%	5 %	M ; N ; O ; Y	O ; Y
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	M ; N ; O ; Y	N
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	M ; N ; O ; Y	O ; Y
Klisyri	tirbanibulin ointment	1 %	M ; N ; O ; Y	N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

	Diclofenac Sodium (Actinic Keratoses) Gel 3%	3 %	300	Grams	90	DAYS
	Diclofenac Sodium (Actinic Keratoses) Gel 3%	3 %	300	Grams	90	DAYS
	Imiquimod Cream 5%	5 %	48	Packets	112	DAYS
	Imiquimod Cream 5%	5 %	48	Packets	112	DAYS
Carac ; Fluorouracil	Fluorouracil Cream 0.5%	0.5 %	30	Grams	28	DAYS
Carac ; Fluorouracil	Fluorouracil Cream 0.5%	0.5 %	30	Grams	28	DAYS
Efudex	Fluorouracil Cream 5%	5 %	240	Grams	84	DAYS
Efudex	Fluorouracil Cream 5%	5 %	240	Grams	84	DAYS
Klisyri	Tirbanibulin Ointment	1 %	5	Packets	90	DAYS
Klisyri	Tirbanibulin Ointment	1 %	5	Packets	90	DAYS
Tolak	Fluorouracil Cream 4%	4 %	40	Grams	28	DAYS
Tolak	Fluorouracil Cream 4%	4 %	40	Grams	28	DAYS
Zyclara	imiquimod cream	3.75 %	56	Packets	42	DAYS			51672417406;99207027028
Zyclara	imiquimod cream	3.75 %	56	Packets	42	DAYS			51672417406;99207027028
Zyclara pump	imiquimod cream	3.75 %	2	Bottles	42	DAYS			00093313331;51672417409;63629881801 ; 68682027275 ; 99207027175
Zyclara pump	imiquimod cream	3.75 %	2	Bottles	42	DAYS			00093313331;51672417409;63629881801 ; 68682027275 ; 99207027175
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	2	Bottles	42	DAYS
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	2	Bottles	42	DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
		5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
	diclofenac sodium (actinic keratoses) gel	3 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Carac ; Fluorouracil	Fluorouracil Cream 0.5%	0.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Efudex	Fluorouracil Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Klisyri	tirbanibulin ointment	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Tolak	Fluorouracil Cream 4%	4 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
	Diclofenac Sodium (Actinic Keratoses) Gel 3%	3 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
	Diclofenac Sodium (Actinic Keratoses) Gel 3%	3 %	NetResults A Series
	Imiquimod Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
	Imiquimod Cream 5%	5 %	NetResults A Series
Carac ; Fluorouracil	Fluorouracil Cream 0.5%	0.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Carac ; Fluorouracil	Fluorouracil Cream 0.5%	0.5 %	NetResults A Series
Efudex	Fluorouracil Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Efudex	Fluorouracil Cream 5%	5 %	NetResults A Series
Klisyri	Tirbanibulin Ointment	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Klisyri	Tirbanibulin Ointment	1 %	NetResults A Series
Tolak	Fluorouracil Cream 4%	4 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Tolak	Fluorouracil Cream 4%	4 %	NetResults A Series
Zyclara	imiquimod cream	3.75 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Zyclara	imiquimod cream	3.75 %	NetResults A Series
Zyclara pump	imiquimod cream	3.75 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Zyclara pump	imiquimod cream	3.75 %	NetResults A Series
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx ; SourceRx-Performance
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	NetResults A Series

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
PA	Target Agent(s) will be approved when ALL of the following are met: If the patient has an FDA labeled indication, then ONE of the following: The patient’s age is within FDA labeling for the requested indication for the requested agent OR There is support for using the requested agent for the patient’s age for the requested indication AND ONE of the following: BOTH of the following: The patient has a diagnosis of actinic (solar) keratoses of the face and/or scalp: AND The requested agent is diclofenac 3% gel, Carac (fluorouracil) 0.5% cream, Efudex (fluorouracil) 5% cream, Tolak (fluorouracil) 4% cream, Aldara (imiquimod) 5% cream, Zyclara (imiquimod) 3.75% cream, Zyclara (imiquimod) 2.5% cream, or Klisyri (tirbanibulin) 1% ointment OR BOTH of the following: The patient has a diagnosis of actinic (solar) keratoses of the trunk and/or extremities: AND The requested agent is diclofenac 3% gel or Efudex (fluorouracil) 5% cream OR BOTH of the following: The patient has a diagnosis of superficial basal cell carcinoma AND The requested agent is Aldara (imiquimod) 5% cream or Efudex (fluorouracil) 5% cream OR BOTH of the following: The patient has a diagnosis of external genital and/or perianal warts (EGW)/ condyloma acuminata AND The requested agent is Aldara (imiquimod) 5% cream or Zyclara (imiquimod) 3.75% cream AND ONE of the following: For a diagnosis of actinic keratoses or superficial basal cell carcinoma, the patient has ONE of the following: Tried and had an inadequate response to generic imiquimod 5% cream or fluorouracil solution OR An intolerance or hypersensitivity to therapy with generic imiquimod 5% cream or fluorouracil solution OR An FDA labeled contraindication to generic imiquimod 5% cream AND fluorouracil solution OR For a diagnosis of external genital warts, the patient has ONE of the following: Tried and had an inadequate response to generic imiquimod 5% cream OR An intolerance of hypersensitivity to therapy with generic imiquimod 5% cream OR An FDA labeled contraindication to generic imiquimod 5% cream Length of Approval: 4 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. *Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Module

Clinical Criteria for Approval

Target Agent(s) will be approved when ALL of the following are met:

If the patient has an FDA labeled indication, then ONE of the following:
1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
2. There is support for using the requested agent for the patient’s age for the requested indication AND
ONE of the following:
1. BOTH of the following:
  1. The patient has a diagnosis of actinic (solar) keratoses of the face and/or scalp: AND
  2. The requested agent is diclofenac 3% gel, Carac (fluorouracil) 0.5% cream, Efudex (fluorouracil) 5% cream, Tolak (fluorouracil) 4% cream, Aldara (imiquimod) 5% cream, Zyclara (imiquimod) 3.75% cream, Zyclara (imiquimod) 2.5% cream, or Klisyri (tirbanibulin) 1% ointment OR
2. BOTH of the following:
  1. The patient has a diagnosis of actinic (solar) keratoses of the trunk and/or extremities: AND
  2. The requested agent is diclofenac 3% gel or Efudex (fluorouracil) 5% cream OR
3. BOTH of the following:
  1. The patient has a diagnosis of superficial basal cell carcinoma AND
  2. The requested agent is Aldara (imiquimod) 5% cream or Efudex (fluorouracil) 5% cream OR
4. BOTH of the following:
  1. The patient has a diagnosis of external genital and/or perianal warts (EGW)/ condyloma acuminata AND
  2. The requested agent is Aldara (imiquimod) 5% cream or Zyclara (imiquimod) 3.75% cream AND
ONE of the following:
1. For a diagnosis of actinic keratoses or superficial basal cell carcinoma, the patient has ONE of the following:
  1. Tried and had an inadequate response to generic imiquimod 5% cream or fluorouracil solution OR
  2. An intolerance or hypersensitivity to therapy with generic imiquimod 5% cream or fluorouracil solution OR
  3. An FDA labeled contraindication to generic imiquimod 5% cream AND fluorouracil solution OR
2. For a diagnosis of external genital warts, the patient has ONE of the following:
  1. Tried and had an inadequate response to generic imiquimod 5% cream OR
  2. An intolerance of hypersensitivity to therapy with generic imiquimod 5% cream OR
  3. An FDA labeled contraindication to generic imiquimod 5% cream

Length of Approval: 4 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
QL	Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) does NOT exceed the program quantity limit OR There is support for therapy with the requested quantity (dose) for the requested indication Length of Approval: up to 12 months

Module

Clinical Criteria for Approval

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

The requested quantity (dose) does NOT exceed the program quantity limit OR
There is support for therapy with the requested quantity (dose) for the requested indication

Length of Approval: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.