What are the recommended medications for treating Actinic Keratoses?

Recommended Medications for Actinic Keratoses

For field treatment of actinic keratoses, use topical 5-fluorouracil (5-FU) or imiquimod as first-line therapy, with 5-FU being particularly effective when combined with calcipotriol for enhanced clearance. 1

First-Line Topical Medications

5-Fluorouracil (5-FU) - Strongly Recommended

The American Academy of Dermatology strongly recommends field treatment with topical 5-FU for actinic keratoses based on moderate-quality evidence. 1

Dosing Regimens:

• 5% 5-FU cream: Apply twice daily for 2-4 weeks until inflammatory response reaches erosion stage 2
• 0.5% 5-FU cream: Apply once daily for 7-28 days 1
• 0.5% 5-FU with 10% salicylic acid: Apply daily for 6-12 weeks, particularly effective for hyperkeratotic lesions 1

Efficacy data shows 5% 5-FU achieves 38% complete clearance at 6 months versus 17% with placebo (P<0.01). 1 The 0.5% concentration demonstrates 67% reduction in lesion count and is better tolerated than 5% formulation while maintaining comparable efficacy. 3

Enhanced regimen: 5-FU combined with calcipotriol for 4 consecutive days produces superior results—87.8% mean reduction on face, 76.4% on scalp, and 27% complete clearance versus 0% with 5-FU alone (P<0.0001). 1 This combination causes more redness (69% vs 25%) and burning (39% vs 13%) but requires confirmatory studies. 1

Imiquimod - Strongly Recommended

The American Academy of Dermatology strongly recommends field treatment with imiquimod based on moderate-to-high quality evidence. 1

Available Concentrations and Dosing:

• 5% imiquimod cream: Apply 2-3 times weekly for 4-16 weeks 1, 4

  • Standard regimen: 3 times weekly for 4 weeks, repeat for additional 4 weeks if needed 1
  • Complete clearance rates: 29.3% (9-24 doses) to 40.8% (32-56 doses) 1

• 3.75% imiquimod cream: Apply daily for 2-week cycles (2 weeks on, 2 weeks off, 2 weeks on) 1

• 2.5% imiquimod cream: Apply daily for 4-6 week cycles 1

Apply at night and wash off after 8 hours. 1 Licensed for clinically typical, non-hyperkeratotic actinic keratoses on face or scalp in immunocompetent adults. 4

Adverse effects: Severe local skin reactions occur in 20.6-41.5% of patients; influenza-like symptoms in 3.7%; discontinuation due to adverse events in only 0.6-1.2%. 1

Second-Line Topical Medication

Diclofenac 3% Gel - Conditionally Recommended

The American Academy of Dermatology conditionally recommends diclofenac based on lower quality evidence than 5-FU or imiquimod. 1

• Dosing: Apply 2.5-3% diclofenac in hyaluronic acid gel twice daily for 60-90 days 1
• Efficacy: Achieves 32% complete clearance at 8 weeks post-treatment 1
• Black box warning: NSAIDs carry cardiovascular and gastrointestinal side-effect warnings 1

Combination Therapy Recommendations

For patients requiring enhanced efficacy, combine topical agents with cryosurgery:

• 5-FU plus cryosurgery: Conditionally recommended over cryosurgery alone (moderate-quality evidence) 1
• Imiquimod plus cryosurgery: Conditionally recommended over cryosurgery alone (low-quality evidence) 1
• Diclofenac plus cryosurgery: Conditionally recommended AGAINST—no added benefit 1

Important Clinical Considerations

Patient counseling is critical: Over 90% of patients treated with 0.5% 5-FU/salicylic acid experience irritation. 1 Warn patients about expected erythema, vesiculation, desquamation, and erosion before re-epithelialization occurs. 2 Complete healing may take 1-2 months after stopping therapy. 2

Treatment duration flexibility: Short 1-week courses of 0.5% 5-FU are effective and well-tolerated, with no serious adverse events or treatment discontinuations. 5 However, extending treatment to 4 weeks improves clearance rates. 5

Avoid poor healing sites: Use extreme caution applying 5-FU to lower legs due to ulceration risk; consider supervision and compression bandaging. 1

Ingenol mebutate withdrawn: Market authorization was withdrawn in the European Union after data showed 3-times higher skin cancer incidence at 3 years (6.3%) compared to imiquimod (2%). 1 This agent should not be used.

Maintenance therapy: Actinic keratosis is a chronic disease requiring ongoing management. 1 Patients should be educated about self-care, sun protection, and monitoring for new lesions or transformation to squamous cell carcinoma. 1