New ointment provides steroid-free option for patients with eczema

Fujisawa's Protopic treats eczema


Rx Care

New ointment provides steroid-free option for eczema patients

The first new type of drug in decades to treat the troubling skin disease atopic dermatitis (AD), commonly known as eczema, has received Food & Drug Administration approval. Manufactured by Fujisawa Healthcare Inc., Protopic (tacrolimus) is the first in a new class of drugs called topical immunomodulators, or TIMs, which offers a steroid-free option for the treatment of moderate to severe AD. Tacrolimus had already been available in oral and intravenous versions for helping to prevent rejection in organ transplant recipients.

Conventional therapies for eczema have been limited and variable outcomes have been reported. Topical corticosteroids have been the mainstay of therapy for AD because of their broad immunomodulatory effects. However, topical corticosteroids are not ideal agents, particularly in children, because, when used over the long term, they have the potential to cause skin atrophy and, with more potent preparations, systemic adverse effects. "The medical community is constantly looking for new therapeutic options for the treatment of eczema," said Amy Paller, pediatric dermatologist at Children's Memorial Hospital, Chicago. The FDA's "recommendations regarding the use of Protopic ... takes prescribing physicians one step closer to a steroid-free alternative to help treat all age groups suffering from eczema."


The FDA based its approval of tacrolimus on the results of three 12-week studies that indicated that 28%-37% of patients using tacrolimus experienced greater than or equal to 90% improvement of their skin condition, as measured by physicians. The agency also took into account two one-year studies that indicated the drug is safe for intermittent long-term use. U.S. clinical trials included randomized, double-blind, placebo-controlled 12-week studies with patients suffering from moderate to severe eczema. Patients in the study were randomized to apply either 0.03% or 0.1% tacrolimus ointment or placebo as a thin layer twice daily on their skin. More than one-third of the patients were children (as young as 24 months of age). The study data reported that both concentrations of tacrolimus ointment significantly improved or completely cleared the signs and symptoms of the disease in more than two-thirds of the patients.

Mark Boguniewicz, M.D., associate professor of pediatrics at the University of Colorado Health Sciences Center in Denver, provided an update on new immunomodulating agents at the recent American Academy of Allergy, Asthma & Immunology's 56th annual meeting. "This medicine [tacrolimus ointment] has been evaluated extensively in clinical trials and appears to have several distinct advantages over corticosteroid preparations. First, there is little or no systemic absorption when it is used as a 0.03% to 0.1% ointment. Moreover, skin absorption is reduced in normal skin, so that as the skin begins to improve, absorption is progressively diminished. Second, the safety profile is excellent, there is no effect on collagen synthesis, and skin atrophy has not been observed."

In patients with AD or other chronic inflammatory dermatoses there is a series of complex immunodysregulatory activities that take place. T lymphocytes are activated, release cytokines, and interact with a broad range of other cell types in the dermis and epidermis. The mechanism of action of tacrolimus is calcinuerin inhibition, which results in suppression of antigen-specific T cells and inhibition of inflammatory cytokine release.

Common side effects associated with the topical use of tacrolimus include temporary stinging or burning sensations where the drug is applied, which may lessen if the diseased skin heals. Evidence from one animal study suggested the tacrolimus ointment might accentuate the adverse effects of ultraviolet light on the skin. Therefore, it is important that patients avoid sunlight and sun lamps, tanning beds, and treatment with UVA or UVB light. Patients who need to be outdoors after applying tacrolimus ointment should wear loose-fitting clothing that protects the treated area from the sun.

Tacrolimus is not a cure. Once patients stopped using the cream, eczema gradually returned. So far, the FDA has determined only that using the medication for a year is safe; long-term open-label testing by Fujisawa is ongoing.

The 0.1% concentration of tacrolimus is recommended for the treatment of adults, while the lower 0.03% concentration is for treatment in both children and adults for long-term intermittent therapy in patients not adequately responsive to, or intolerant of, conventional therapy. The drug is expected to be available in the first quarter of 2001. According to a company spokesman, pricing will be competitive with moderate- to high-potency corticosteroids.

Besides tacrolimus ointment, another eczema treatment could be coming shortly. It's ASM 981 Cream 1%, another nonsteroidal dermatologic for AD. Novartis recently filed a new drug application for this agent.

Tammy Chernin, R.Ph.


  • Protopic should not be used by patients who are allergic to its active ingredient, tacrolimus, or its inactive ingredients.

  • Women who are breastfeeding should also avoid this drug.

  • Advise women who are pregnant or who are planning to become pregnant to check with their physicians before using this product.

  • Patients should use safe sun practices to avoid exposure to natural or artificial sunlight. Because Protopic affects the immune system, it might increase the risk of sun cancer. The possibility remains under study.

  • Skin infections should be healed before patients start to use Protopic.

  • Most common side effects were skin burning or tingling in up to 60% of patients. But after a month of use, less than 10% reported a continuation of the side effects.


Tammy Chernin. New ointment provides steroid-free option for patients with eczema. Drug Topics 2001;2:23.