Pharmacology Update
Pimecrolimus Cream 1% (Elidel—Novartis)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Novartis pharmaceuticals is ready to market pimecrolimus cream for the treatment of atopic dermatitis. The drug is an immune modulator similar to tacrolimus topical (Protopic), which was also recently approved for this indication. Both of these agents are calcineurin inhibitors and are believed to have the same mechanisms of action. Pimecrolimus cream will be marketed by Novartis under the trade name "Elidel."
Indications
Pimecrolimus is indicated for the short-term and intermittent long-term therapy of mild-to-moderate atopic dermatitis in nonimmunocompromised patients 2 years of age and older. It is recommended for patients in whom alternative, conventional therapies were not effective or not appropriate due to intolerance or potential risk.1
Dosage
A thin layer should be applied to the affected skin twice daily and should be rubbed in gently and completely. Pimecrolimus can be applied to all skin surfaces. After symptoms have resolved, therapy should be discontinued and may be resumed at the first sign of recurrence. If symptomatic improvement does not occur within 6 weeks, the condition should be re-evaluated. Patients should be advised to minimize exposure to ultraviolet A or B light either natural or artificial.1
Potential Advantages
In vitro data indicate that pimecrolimus has one-tenth the skin penetration of tacrolimus.2 This may lead to lower systemic bioavailability. With twice-daily application in 12 patients with extensive atopic dermatitis, 78% of 444 blood samples evaluated were below the limit of the assay (0.5 ng/mL).3
Potential Disadvantages
Pimecrolimus is indicated for mild-to-moderate atopic dermatitis while tacrolimus is indicated for moderate-to-severe disease. In patients with at least moderate disease, pimecrolimus was reported to be less effective than 0.1% betamethasone valerate cream at 3 weeks.4 Similar to tacrolimus, pimecrolimus is associated with an increased risk of chicken pox, shingles, or eczema herpeticum. Lymphadenopathy has also been reported (0.9%). Application site reactions (eg, warmth or burning sensation) occur in 8-26% of patients.1
Comments
Pimecrolimus, an ascomycin derivative, is a topical immunomodulator. Its mechanisms of action appeared to include inhibiting the catalytic function of calcineurin and binding to macrophilin-12 resulting in suppressed T-cell activation.1,8 In vitro data demonstrate a reduced production and release of proinflammatory cytokines from T cells and histamine from mast cells.1,5,6 Pimecrolimus can be applied to any skin surface and does not appear to be atrophogenic.1,4 The drug has been studied in vehicle controlled trials in mild-to-moderate atopic dermatitis. In 2 6-week studies (n = 403), 10% of patients were cleared of the disease compared to 4% for the vehicle, 35% vs. 18% clear or almost clear, and 67% vs. 40% clear to mild disease.1 Fifty-nine percent had moderate disease, mean body surface involvement was 26%, and about 75% had disease affecting the face and/or neck region. Optimal effect was achieved in about 30 days. In a one-year study, pimecrolimus, when applied at the first sign of eczema, resulted in 50% of patients avoiding the progression of atopic dermatitis to flares.7
There are no published comparative studies between pimecrolimus and tacrolimus.
Pimecrolimus cream is priced about $34 for 30 g and $106 for 100 g.
Clinical Implications
Atopic dermatitis is a chronic relapsing inflammatory skin disease affecting up to 10-20% of children. It is characterized by erythematous scaling papules and plaques, and intensive itching.8 Topical corticosteroids have been the mainstays of therapy. Pimecrolimus along with tacrolimus offer alternatives to topical corticosteroids. These agents are steroid sparing, are safe in children, can be used on the face and intertriginous areas, and do not appear to cause skin atrophy or systemic toxicity. v
References
1. Elidel Cream Product Information. December 2001. Novartis Pharmaceuticals Corp.
2. Stuetz A, et al. Semin Cutan Med Surg. 2001;20(4): 233-241.
3. Van Leent EJ, et al. Dermatology. 2002;204(1):63-68.
4. Luger T, et al. Br J Dermatol. 2001;144:788-794.
5. Zuberbier T, et al. J Allergy Clin Immunol. 2001; 108(2):275-280.
6. Grassberger M, et al. Br J Dermatol. 1999;141(2): 267-273.
7. Hebert AA, et al. Semin Cutan Med Surg. 2001;20(4): 260-267.
8. Paller AS. J Pediatr. 2001;138(2):163-168.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
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