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ph-1037

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

Policy Number: PH-1037

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

The quantity limit program applies to NetResults A series formulary.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
04-01-2024

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Aldara® (imiquimod) 5% cream*	Topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses 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 (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 Treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites	* generic available	4
Fluoroplex® (fluorouracil) 1% cream	Topical treatment of multiple actinic (solar) keratoses		3
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 full face or balding scalp in immunocompetent adults Treatment of external genital and perianal warts (EGW)/condyloma acuminata in patients 12 years or older	* generic available	7
Zyclara® (imiquimod) 2.5% cream	Topical treatment of clinically typical visible or palpable actinic keratoses (AK) of the full 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 NCCN guidelines, topical first-line therapies for AK include 5-fluorouracil (5-FU), imiquimod, and tirbanibulin. 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) UpToDate indicates 5-FU and imiquimod as first-line topical therapies, and diclofenac and tirbanibulin as second-line.
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.(11) 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 rate may be lower.(11,12)
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% and 5%, and podophyllotoxin.(13,14) The majority of genital warts respond within 3 months of therapy.(14)

REFERENCES

Number	Reference
1	Diclofenac 3% gel prescribing information. Glenmark Pharmaceuticals Inc. June 2016.
2	Carac 0.5% cream prescribing information. Bausch Health US, LLC. May 2021.
3	Fluoroplex prescribing information. Almirall, LLC. March 2022.
4	Efudex prescribing information. Bausch Health Companies Inc. October 2021.
5	Tolak prescribing information. Hill Dermaceuticals, Inc. March 2020.
6	Aldara prescribing information. Valeant Pharmaceuticals International, Inc. June 2022.
7	Zyclara prescribing information. Bausch Health US, LLC. June 2020.
8	Klisyri prescribing information. Almirall, LLC. August 2021.
9	Berman B, et al. Treatment of Actinic Keratosis. UpToDate. Last updated February 2023. Literature review current through June 2023.
10	National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Squamous Cell Skin Cancer. Version 1.2023.
11	Aasi SZ, et al. Treatment and Prognosis of Basal Cell Carcinoma at Low Risk of Recurrence. UpToDate. Last updated December 2022. Literature review current through June 2023.
12	National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. Version 1.2023.
13	Rosen T, et al. Condylomata Acuminata (Anogenital Warts): Management of External Condylomata Acuminata in Adult Males. UpToDate. Last updated February 2023. Literature review current through June 2023.
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.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

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

	diclofenac sodium (actinic keratoses) gel	3 %	M ; N ; O ; Y	Y
Carac	Fluorouracil Cream 0.5%	0.5 %	M ; N ; O ; Y	M
Fluoroplex	Fluorouracil Cream 1%	1 %	M ; N ; O ; Y	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
Aldara	Imiquimod Cream 5%	5 %	M ; N ; O	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
Quantity Limit
	diclofenac sodium (actinic keratoses) gel	3 %	300	Grams	90	DAYS
Aldara	Imiquimod Cream 5%	5 %	48	Packets	112	DAYS
Carac	Fluorouracil Cream 0.5%	0.5 %	30	Grams	28	DAYS
Efudex	Fluorouracil Cream 5%	5 %	240	Grams	84	DAYS
Fluoroplex	Fluorouracil Cream 1%	1 %	60	Grams	42	DAYS
Klisyri	Tirbanibulin Ointment	1 %	5	Packets	90	DAYS
Tolak	Fluorouracil Cream 4%	4 %	40	Grams	28	DAYS
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	2	Bottles	56	DAYS
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	56	Packets	56	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
			Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
	diclofenac sodium (actinic keratoses) gel	3 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Aldara	Imiquimod Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Carac	Fluorouracil Cream 0.5%	0.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Efudex	Fluorouracil Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Fluoroplex	Fluorouracil Cream 1%	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Klisyri	tirbanibulin ointment	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Tolak	Fluorouracil Cream 4%	4 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
	diclofenac sodium (actinic keratoses) gel	3 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
	diclofenac sodium (actinic keratoses) gel	3 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Aldara	Imiquimod Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Aldara	Imiquimod Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Carac	Fluorouracil Cream 0.5%	0.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Carac	Fluorouracil Cream 0.5%	0.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Efudex	Fluorouracil Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Efudex	Fluorouracil Cream 5%	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Fluoroplex	Fluorouracil Cream 1%	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Fluoroplex	Fluorouracil Cream 1%	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Klisyri	Tirbanibulin Ointment	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Klisyri	Tirbanibulin Ointment	1 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Tolak	Fluorouracil Cream 4%	4 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Tolak	Fluorouracil Cream 4%	4 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Zyclara ; Zyclara pump	Imiquimod Cream 3.75%	3.75 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Zyclara pump	Imiquimod Cream 2.5%	2.5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
Prior Authorization with Quantity Limit	Target Agent(s) will be approved when ALL of the following are met: If the patient has an FDA approved indication, then ONE of the following: The patient’s age is within FDA labeling for the requested indication for the requested agent OR The prescriber has provided information in support of 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, Fluoroplex, Tolak, Aldara, Zyclara (Imiquimod) 3.75% cream, Zyclara 2.5% cream, OR Klisyri 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, Efudex (Fluorouracil) 5% cream, OR Fluoroplex OR BOTH of the following: The patient has a diagnosis of superficial basal cell carcinoma AND The requested agent is Aldara 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 OR Zyclara (Imiquimod) 3.75% cream AND ONE of the following: For a diagnosis of actinic keratoses or superficial basal cell carcinoma, ONE of the following: The patient has tried and had an inadequate response to generic imiquimod 5% cream or fluorouracil solution OR The patient has an intolerance or hypersensitivity to therapy with generic imiquimod 5% cream or fluorouracil solution OR The patient has an FDA labeled contraindication to generic imiquimod 5% cream AND fluorouracil solution OR For a diagnosis of external genital warts, ONE of the following: The patient has tried and had an inadequate response to generic imiquimod 5% cream OR The patient has an intolerance of hypersensitivity to therapy with generic imiquimod 5% cream OR The patient has an FDA labeled contraindication to generic imiquimod 5% cream Length of Approval: Up to duration in the program quantity limit for the requested indication; or durations above program quantity limit with appropriate supportive information for up to 12 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

Prior Authorization with Quantity Limit

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

If the patient has an FDA approved 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. The prescriber has provided information in support of 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, Fluoroplex, Tolak, Aldara, Zyclara (Imiquimod) 3.75% cream, Zyclara 2.5% cream, OR Klisyri 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, Efudex (Fluorouracil) 5% cream, OR Fluoroplex OR
3. BOTH of the following:
  1. The patient has a diagnosis of superficial basal cell carcinoma AND
  2. The requested agent is Aldara 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 OR Zyclara (Imiquimod) 3.75% cream AND
ONE of the following:
1. For a diagnosis of actinic keratoses or superficial basal cell carcinoma, ONE of the following:
  1. The patient has tried and had an inadequate response to generic imiquimod 5% cream or fluorouracil solution OR
  2. The patient has an intolerance or hypersensitivity to therapy with generic imiquimod 5% cream or fluorouracil solution OR
  3. The patient has an FDA labeled contraindication to generic imiquimod 5% cream AND fluorouracil solution OR
2. For a diagnosis of external genital warts, ONE of the following:
  1. The patient has tried and had an inadequate response to generic imiquimod 5% cream OR
  2. The patient has an intolerance of hypersensitivity to therapy with generic imiquimod 5% cream OR
  3. The patient has an FDA labeled contraindication to generic imiquimod 5% cream

Length of Approval: Up to duration in the program quantity limit for the requested indication; or durations above program quantity limit with appropriate supportive information for up to 12 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 Standalone	Quantity limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) and/or duration does NOT exceed the program quantity limit for the requested indication OR Information has been provided to support therapy with the requested quantity (dose) and/or duration of therapy for the requested indication Length of Approval: up to 12 months
QL with PA	Quantity limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) and/or duration does NOT exceed the program quantity limit for the requested indication OR Information has been provided to support therapy with the requested quantity (dose) and/or duration of therapy for the requested indication Length of Approval: Up to duration in the program quantity limit for the requested indication; or durations above program quantity limit with appropriate supportive information for up to 12 months

Module

Clinical Criteria for Approval

QL Standalone

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

The requested quantity (dose) and/or duration does NOT exceed the program quantity limit for the requested indication OR
Information has been provided to support therapy with the requested quantity (dose) and/or duration of therapy for the requested indication

Length of Approval: up to 12 months

QL with PA

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

The requested quantity (dose) and/or duration does NOT exceed the program quantity limit for the requested indication OR
Information has been provided to support therapy with the requested quantity (dose) and/or duration of therapy for the requested indication

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.