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Actinic Keratosis Medication

  • Author: James M Spencer, MD; Chief Editor: William D James, MD  more...
Updated: Apr 07, 2016

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.


Antineoplastic Agent, Topical

Class Summary

The drug of choice is topical 5-FU lotion or cream, which inhibits cell growth and proliferation.

Fluorouracil topical (Fluoroplex, Carac, Efudex)


Fluorouracil topical is used topically for the management of actinic keratoses. It interferes with DNA synthesis by blocking methylation of deoxyuridylic acid via inhibition of thymidylate synthetase and, subsequently, cell proliferation. For lesions on bald scalp or extremities, longer treatment is often necessary.

Ingenol mebutate topical (Picato)


The precise mechanism by which ingenol mebutate causes cell death in actinic keratosis is unknown, but it may include a dual action of (1) rapid lesion necrosis by mitochondrial swelling and membrane disruption and (2) specific neutrophil-mediated, antibody-dependent cellular cytotoxicity by antibodies produced from B cells that bind to antigens on dysplastic epidermal cells.

The dosage for actinic keratosis differs depending on the application site. The 0.015% gel is used for application to the face or scalp for 3 consecutive days, whereas the 0.05% gel is used for application to the trunk or extremities for 2 consecutive days.


Immunomodulator, Topical

Class Summary

Investigation of imiquimod demonstrates it induces interferons alpha and gamma, TNF-alpha, and interleukin 12, among other cytokines. Studies using 5% cream in mice showed significant induction of interferon alpha at the site of application, occurring as early as 2 hours after treatment. At 4 hours after application, increases in interferon alpha mRNA levels were found, indicating an increase in transcription. Cytokine up-regulation is thought to be activated by imiquimod binding to toll-like receptor VII.

Imiquimod (Aldara 5% cream, Zyclara 3.75% cream)


Imiquimod is an immune response modifier thought to produce a nonspecific anti–actinic keratosis response, interferon, natural killer cells, and a specific immune response (cytotoxic T cells). It is indicated for clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp.


Photosensitizing Agent, Topical

Class Summary

Topical photosensitizing agents are administered in combination with PDT.

Aminolevulinic acid (Levulan), Methyl aminolevulinate cream (Metvixia)


These agents are porphyrin precursors used in combination with narrow-band, red-light illumination for nonhyperkeratotic, nonpigmented actinic keratoses. When used with PDT, accumulation of photoactive porphyrins produces a photodynamic reaction that results in a cytotoxic process dependent upon the simultaneous presence of oxygen.

PDT with aminolevulinic acid is a 2-stage process involving application of the solution followed by illumination with blue light 14-18 hours later; treatment may be repeated every 8 weeks.

Levulan: Topical solution 20% is intended for direct application to individual lesions diagnosed as actinic keratosis and not to perilesional skin. Application should involve either scalp or face lesions, but not both simultaneously. Recommended treatment frequency is 1 application and 1 dose of illumination per treatment site per 8-week treatment session. Each Levulan Kerastick should be used for only one patient.


Nonsteroidal Anti-inflammatory Drug, Topical

Diclofenac topical (Solaraze)


Diclofenac topical is designated chemically as 2-[(2,6-dichlorophenyl) amino] benzeneacetic acid, monosodium salt, with an empirical formula of C14 H10 Cl2 NO2 Na. It is one of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacological studies. It is believed to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Diclofenac topical can cause hepatotoxicity; hence, liver enzyme levels should be monitored in first 8 weeks of treatment.

It is used topically as a keratolytic agent to treat actinic keratoses.

Contributor Information and Disclosures

James M Spencer, MD Professor of Clinical Dermatology, Mount Sinai School of Medicine; Private Practice, Spencer Dermatology

James M Spencer, MD is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Dermatology, American College of Mohs Surgery, American Medical Association, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, International Society for Dermatologic Surgery

Disclosure: Received grant/research funds from Genentech for independent contractor; Received grant/research funds from DUSA for independent contractor; Received honoraria from Leo Pharmicuticals for review panel membership.


Laura Jordan, DO, MA, MS, MLS Dermatology-Focus Traditional Rotating Intern, UH Regional Hospitals

Laura Jordan, DO, MA, MS, MLS is a member of the following medical societies: American Osteopathic College of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Kelly M Cordoro, MD Assistant Professor of Clinical Dermatology and Pediatrics, Department of Dermatology, University of California, San Francisco School of Medicine

Kelly M Cordoro, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Medical Society of Virginia, Society for Pediatric Dermatology, Women's Dermatologic Society, Association of Professors of Dermatology, National Psoriasis Foundation, Dermatology Foundation

Disclosure: Nothing to disclose.

Michelle Henry, MD Fellow in Procedural Dermatology, Department of Dermatology, Lahey Clinic, Harvard Medical School

Disclosure: Nothing to disclose.


Amy Lynn Basile, DO, MPH Sun Coast Hospital/Largo Medical Center, Largo, Florida

Disclosure: Nothing to disclose.

Mary Farley, MD Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center

Disclosure: Nothing to disclose.

James Fulton Jr, MD, PhD Medical Director, Fulton Skin Institute

Disclosure: Nothing to disclose.

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Actinic keratosis. Courtesy of Hon Pak, MD.
Actinic keratosis during treatment with topical 5-fluorouracil. Courtesy of Hon Pak, MD.
Actinic keratosis right after treatment with topical 5-fluorouracil. Courtesy of Hon Pak, MD.
Erythematous, scaly lesions on the temple area, typical of actinic keratosis.
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