General Information

Protopic (tacrolimus) is a macrolide immunosuppressant.

Protopic Ointment, both 0.03% and 0.1% is indicated for adults, and only 0.03% is indicated for children aged 2 to 15 years, as second-line therapy for the short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non-immunocompromised adults and children who have failed to respond adequately to other topical prescription treatments for atopic dermatitis, or when those treatments are not advisable.

Protopic is supplied as an ointment.

Adults 0.03% and 0.1%

Apply a thin layer of Protopic Ointment to the affected skin twice daily. The minimum amount should be rubbed in gently and completely to control signs and symptoms of atopic dermatitis. Stop using when signs and symptoms of atopic dermatitis resolve.

If signs and symptoms (e.g. itch, rash, and redness) do not improve within 6 weeks, patients should be re-examined by their healthcare provider to confirm the diagnosis of atopic dermatitis.

Continuous long-term use of topical calcineurin inhibitors, including Protopic Ointment should be avoided, and application should be limited to areas of involvement with atopic dermatitis.

The safety of Protopic Ointment under occlusion, which may promote systemic exposure, has not been evaluated. Protopic Ointment should not be used with occlusive dressings.

Pediatrics 2 -15 Years of age Protopic Ointment 0.03%

Apply a thin layer of Protopic Ointment, 0.03% to the affected skin twice daily. The minimum amount should be rubbed in gently and completely to control signs and symptoms of atopic dermatitis. Stop using when signs and symptoms of atopic dermatitis resolve.

If signs and symptoms (e.g. itch, rash, and redness) do not improve within 6 weeks, patients should be re-examined by their healthcare provider to confirm the diagnosis of atopic dermatitis.

Continuous long-term use of topical calcineurin inhibitors, including Protopic Ointment should be avoided, and application should be limited to areas of involvement with atopic dermatitis.

Mechanism of Action

The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This effect has been shown to prevent the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines (such as interleukin-2, gamma interferon). Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-α, all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to down regulate the expression of FcεRI on Langerhans cells.

Clinical Trial Results

Protopic's safety and effectiveness was evaluated in 28 worldwide trials with more than 4,000 adults and children - including those as young as 24 months of age. Trials were conducted in the United States, Europe and Japan, and over one-third of the subjects were children.

The trial data indicated that both concentrations of Protopic significantly improved or cleared the signs and symptoms of the condition in more than two-thirds of the subjects. Many subjects exhibited marked improvement after receiving one week of treatment. Overall, the 0.1% concentration exhibited statistically significant greater efficacy than the 0.03% concentration in adults.