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Chapter: Basic & Clinical Pharmacology : Dermatologic Pharmacology

Immunomodulators

IMIQUIMO, DTACROLIMUS & PIMECROLIMUS

IMMUNOMODULATORS

IMIQUIMOD

Imiquimod is available as 5% cream (Aldara) for the treatment of external genital and perianal warts in adults, actinic keratoses on the face and scalp, and biopsy-proven primary basal cell carcinomas on the trunk, neck, and extremities. A lower 3.75% concentration cream (Zyclara) is available for the treatment of face and scalp actinic keratoses. The mechanism of its action is thought to be related to imiquimod’s ability to stimulate peripheral mononuclear cells to release interferon-α and to stimulate macrophages to produce inter-leukins-1, -6, and -8, and tumor necrosis factor-α (TNF-α).Imiquimod should be applied to the wart tissue three times per week and left on the skin for 6–10 hours prior to washing off with mild soap and water. Treatment should be continued until eradi-cation of the warts is accomplished, but not for more than a total of 16 weeks. Recommended treatment of actinic keratoses consists of twice-weekly applications of the 5% cream on the contiguous area of involvement or nightly applications of the 3.75% cream. The cream is removed after approximately 8 hours with mild soap and water. Treatment of superficial basal cell carcinoma consists of five-times-per-week application to the tumor, including a 1-cm margin of surrounding skin, for a 6-week course of therapy.Percutaneous absorption is minimal, with less than 0.9% absorbed following a single-dose application. Adverse side effects consist of local inflammatory reactions, including pruritus, ery-thema, and superficial erosion.

TACROLIMUS & PIMECROLIMUS

Tacrolimus (Protopic) and pimecrolimus (Elidel) are macrolide immunosuppressants that have been shown to be of significant benefit in the treatment of atopic dermatitis. Both agents inhibit T-lymphocyte activation and prevent the release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen-IgE complexes. Tacrolimus is available as 0.03% and 0.1% ointments, and pimecrolimus is available as a 1% cream. Both are indicated for short-term and intermittent long-term therapy for mild to moderate atopic dermatitis. Tacrolimus 0.03% ointment and pimecrolimus 1% cream are approved for use in children older than 2 years of age, although all strengths are approved for adult use. Recommended dosing of both agents is twice-daily application to affected skin until clearing is noted. Neither medication should be used with occlusive dressings. The most common side effect of both drugs is a burning sensation in the applied area that improves with continued use. The Food and Drug Administration has added a black box warning regarding the long-term safety of topical tacrolimus and pimecrolimus because of animal tumorigenicity data.


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Basic & Clinical Pharmacology : Dermatologic Pharmacology : Immunomodulators |


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