How do you prescribe compounded 5-fluorouracil (5-FU) and calcipotriene for a patient with actinic keratosis or superficial basal cell carcinoma and psoriasis?

Prescribing Compounded 5-FU and Calcipotriene for Actinic Keratosis

For patients with actinic keratosis, prescribe compounded 5-fluorouracil 5% combined with calcipotriene 0.005% ointment applied once daily for 4 consecutive days to the affected field, which achieves superior efficacy (87.8% mean reduction on face, 76.4% on scalp) compared to 5-FU alone while maintaining a short treatment duration. 1

Specific Prescription Details

Formulation and Application

• Compound: 5-fluorouracil 5% + calcipotriene 0.005% in ointment base 1
• Dosing regimen: Apply once daily for 4 consecutive days only 1
• Application technique: Apply thin layer to entire affected field (not just individual lesions), rub in gently and completely 2
• Maximum treatment area: 500 cm² per treatment course due to systemic toxicity concerns with 5-FU 1

Anatomic Site-Specific Efficacy

The combination therapy demonstrates significantly superior lesion reduction compared to 5-FU with vehicle control across all anatomic locations (P < 0.0001 for all sites): 1

• Face: 87.8% reduction (vs 26.3% with 5-FU alone)
• Scalp: 76.4% reduction (vs 5.7% with 5-FU alone)
• Upper extremities: 68.8-79% reduction (vs 9.6-16.3% with 5-FU alone)
• Complete clearance on face: 27% (vs 0% with 5-FU alone)

Clinical Rationale for Combination Therapy

Mechanism of Enhanced Efficacy

The calcipotriene component enhances immune response and T cell-mediated immunity against dysplastic keratinocytes, while 5-FU targets rapidly dividing cells through thymidylate synthetase inhibition. 3, 4 This combination induces tissue-resident memory T (Trm) cell formation in treated skin, which provides long-term immunosurveillance. 4

Long-Term Cancer Prevention Benefit

A prospective cohort study demonstrated that calcipotriene plus 5-FU treatment significantly reduces subsequent squamous cell carcinoma development within 3 years (7% vs 28% in control group, hazard ratio 0.215, P = 0.032), representing a critical mortality and morbidity benefit. 4

Expected Side Effects and Management

Anticipated Local Reactions

The combination therapy produces significantly higher rates of local inflammation compared to 5-FU alone, but this correlates with therapeutic efficacy: 1

• Erythema: 69% (vs 25% with 5-FU alone, P < 0.0001)
• Burning sensation: 39% (vs 13% with 5-FU alone, P = 0.0008)
• Scaling: 14% (vs 7%, not statistically significant)
• Itching: 25% (vs 22%, not statistically significant)

Patient Counseling Requirements

Before initiating treatment, counsel patients extensively about: 1

• Expected soreness, redness, and possible crusting during and after the 4-day treatment period
• Reactions typically peak 7-10 days after completing treatment
• Inflammatory response indicates treatment efficacy
• Permitted to wash area and apply thin emollient during treatment
• If reaction is excessive, weak topical steroid (e.g., hydrocortisone 1%) can be applied 1

Critical Prescribing Considerations

Contraindications and Cautions

• Avoid poor healing sites: Exercise extreme caution on lower legs due to ulceration risk; consider alternative therapy 1
• Periorbital area: Avoid application near eyes 5
• Pregnancy: 5-FU is contraindicated in pregnancy 6
• Dihydropyrimidine dehydrogenase (DPD) deficiency: Screen for history of severe reactions to fluoropyrimidines 6

When NOT to Use This Combination

Do not prescribe compounded 5-FU/calcipotriene for: 6

• Nodular or infiltrative basal cell carcinoma (surgery preferred with nearly 100% success rate)
• Invasive squamous cell carcinoma
• Single, easily accessible lesions where cryosurgery would be more appropriate 5

Alternative Regimens if Combination Unavailable

Standard 5-FU Monotherapy Options

If compounded combination is not accessible: 1, 5

• 5% 5-FU cream: Apply twice daily for 2-4 weeks (achieves 38% complete clearance at 6 months)
• 0.5% 5-FU in 10% salicylic acid: Apply once daily for 7-28 days (achieves 55-77% clearance, better tolerated)

Calcipotriene Dosing for Psoriasis Component

For patients with concurrent psoriasis, calcipotriene monotherapy is applied once or twice daily as a thin layer for chronic management, which differs from the short 4-day pulsed regimen used in combination with 5-FU. 2

Monitoring and Follow-Up

Post-Treatment Assessment

• Evaluate treatment response 4-8 weeks after completing the 4-day course 1
• Expect continued inflammatory response for 1-2 weeks post-treatment
• Assess for complete clearance, partial response, or treatment failure
• Biopsy any persistent thick or suspicious lesions to rule out invasive carcinoma 1

Recurrence Risk

Actinic keratosis has up to 50% recurrence rate within the first year, requiring ongoing surveillance and repeat treatment courses as needed. 7 The combination therapy's induction of persistent Trm cells may reduce this recurrence risk compared to standard 5-FU monotherapy. 4