What are the sig (prescription) instructions for Actikerall (fluorouracil)?

From the Guidelines

Actikerall (fluorouracil) should be applied twice daily for 4 weeks, with the option to titrate the frequency of application against reaction, tolerance, and efficacy, as supported by the British Association of Dermatologists' guidelines 1. The application of Actikerall can be adjusted based on the patient's response, with less frequent initial use enabling the titration of frequency against reaction, tolerance, and efficacy.

• Key points to consider when prescribing Actikerall include:
  • Counseling patients about potential side effects, such as soreness, redness, and crusting, and informing them that these can be minimized by reducing the frequency of application or taking short breaks in the course of therapy.
  • Permitting patients to wash the area and apply a thin emollient to reduce irritation.
  • Considering the use of a weak steroid if the reaction is excessive.
  • Ensuring patients understand how to use the treatment, as they may require it intermittently in the future. The British Association of Dermatologists' guidelines recommend a strength of recommendation A, level of evidence 1++ for the use of 5-fluorouracil (5-FU) cream, with the majority of data relating to the 5% concentration 1.
• Important considerations for the use of Actikerall include:
  • Use with caution at poor healing sites, such as the lower leg, and potentially supervising treatment in these areas.
  • The option to prescribe 5-FU 0.5% in 10% salicylic acid as an alternative.
  • The potential for pulsed therapy to enable more protracted treatment with reduced morbidity, particularly for sensitive areas or patients reluctant to use treatments that provoke redness and crusting.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION: When Fluorouracil Cream USP is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion, and re-epithelialization. Fluorouracil Cream USP should be applied preferably with a nonmetal applicator or suitable glove If Fluorouracil Cream USP is applied with the fingers, the hands should be washed immediately afterward. Actinic or Solar Keratosis: Apply cream twice daily in an amount sufficient to cover the lesions. Medication should be continued until the inflammatory response reaches the erosion stage, at which time use of the drug should be terminated. The usual duration of therapy is from 2 to 4 weeks Complete healing of the lesions may not be evident for 1 to 2 months following cessation of Fluorouracil Cream USP therapy. Superficial Basal Cell Carcinomas: Only the 5% strength is recommended. Apply cream twice daily in an amount sufficient to cover the lesions. Treatment should be continued for at least 3 to 6 weeks. Therapy may be required for as long as 10 to 12 weeks before the lesions are obliterated. The prescription instructions for Actikerall (fluorouracil) are to apply the cream twice daily in an amount sufficient to cover the lesions. For Actinic or Solar Keratosis, treatment should be continued until the inflammatory response reaches the erosion stage, usually for 2 to 4 weeks. For Superficial Basal Cell Carcinomas, treatment should be continued for at least 3 to 6 weeks, and may require up to 10 to 12 weeks 2.

• Apply cream with a nonmetal applicator or suitable glove
• Wash hands immediately after application if using fingers
• Continue treatment until the desired response is achieved, then terminate use.

From the Research

Sig Instructions for Actikerall

The sig instructions for Actikerall (fluorouracil) are as follows:

• Apply once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm) 3
• Treatment duration is up to 12 weeks 3
• Local application site reactions are common, including inflammation and pruritus, but no serious adverse effects have been reported to date 3

Alternative Treatment Regimens

Alternative treatment regimens for Actikerall include:

• Sequential treatment with Solaraze gel (3% diclofenac sodium in 2.5% hyaluronic acid) twice daily for 12 weeks, followed by a 2-week treatment-free interval, then Actikerall cutaneous solution once daily for up to 6 weeks as required 4
• Treatment with 0.5% fluorouracil cream once daily for up to 4 weeks 5
• Treatment with a novel formulation of 4% 5-Fluorouracil cream once daily for 30 consecutive days 6

Comparison with Other Treatments

Actikerall has been compared to other treatments, including:

• Diclofenac 3% gel in hyaluronic acid, which was shown to be less effective than Actikerall in a phase III trial 3
• Topical diclofenac, which has been shown to be moderately effective in actinic keratosis, but less effective than fluorouracil 7