Side Effects of Elidel (pimecrolimus)

Elidel (pimecrolimus) is an immunosuppressant used to treat atopic dermatitis (eczema), a skin condition characterized by

• redness,
• itching,
• scaling, and
• inflammation of the skin.

Scientists believe atopic dermatitis may be due to activation of the immune system by various environmental or emotional triggers.

It is not known exactly how Elidel reduces the manifestations of atopic dermatitis, but Elidel reduces the action of T-cells and mast cells which are part of the immune system and contribute to responses of the immune system.

Elidel prevents the activation of T-cells by blocking the effects of chemicals (cytokines) released by the body that stimulate T-cells. Elidel also reduces the ability of mast cells to release chemicals that promote inflammation. 

Common side effects of Elidel include

• application site reactions (burning, itching, and redness),
• sore throat,
• stuffy nose,
• headache,
• cough,
• respiratory tract and viral infections.

Serious side effects of Elidel include

• skin cancer and
• lymphoma (rare).

Drug interactions of Elidel and other drugs have not been studied. Since very little Elidel is absorbed from the skin, drug interactions are not expected.

Since some Elidel is absorbed, caution should be exercised when Elidel is used by individuals also taking drugs that inhibit the liver enzymes that eliminate Elidel and could increase the levels of Elidel and promote its toxicity such as

• ketoconazole,
• itraconazole,
• erythromycin,
• fluconazole,
• calcium channel blockers, and
• cimetidine.

There are no adequate studies that evaluate the use of Elidel during pregnancy. Use of Elidel by nursing mothers has not been evaluated, and it is unknown if Elidel is excreted in breast milk. Breastfeeding mothers should decide whether to stop nursing or use alternative treatments.

The most common side effects of pimecrolimus are:

• reactions at the site of application,
• burning,
• itching, and
• redness.

Other important side effects include:

• sore throat,
• stuffy nose,
• headache,
• cough,
• respiratory tract and
• viral infections.

Skin cancer and lymphoma have rarely occurred during treatment with pimecrolimus. Therefore, pimecrolimus should not be used for long-term treatment and should only be applied to affected areas.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

No phototoxicity and no photoallergenicity were detected in clinical trials with 24 and 33 normal volunteers, respectively. In human dermal safety trials, Elidel (pimecrolimus) Cream, 1% did not induce contact sensitization or cumulative irritation.

In a one-year safety trial in pediatric subjects age 2-17 years old involving sequential use of Elidel Cream, 1% and a topical corticosteroid, 43% of Elidel Cream, 1% treated subjects and 68% of vehicle -treated subjects used corticosteroids during the trial.

• Corticosteroids were used for more than 7 days by 34% of Elidel Cream, 1% treated subjects and 54% of vehicle -treated subjects.
• An increased incidence of impetigo, skin infection, superinfection (infected atopic dermatitis), rhinitis, and urticaria were found in the subjects that had used Elidel Cream, 1% and topical corticosteroid sequentially as compared to Elidel Cream, 1% alone.

In 3 randomized, double-blind vehicle-controlled pediatric trials and one active-controlled adult trial, 843 and 328 subjects respectively, were treated with Elidel Cream, 1%.

• In these clinical trials, 48 (4%) of the 1,171 Elidel treated subjects and 13 (3%) of 408 vehicle-treated subjects discontinued therapy due to adverse events.
• Discontinuations for AEs were primarily due to application site reactions, and cutaneous infections.
• The most common application site reaction was application site burning, which occurred in 8%-26% of subjects treated with Elidel Cream, 1%.

Table 1 depicts the incidence of adverse events pooled across the 2 identically designed 6-week trials with their open label extensions and the 1-year safety trial for pediatric subjects ages 2-17. Data from the adult active-controlled trial is also included in Table 1. Adverse events are listed regardless of relationship to trial drug.

Table 1: Treatment Emergent Adverse Events ( ≥ 1%) in Elidel® Treatment Groups

Two cases of septic arthritis have been reported in infants less than one year of age in clinical trials conducted with Elidel Cream, 1% (n = 2,443). Causality has not been established.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Elidel Cream, 1%. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General

Anaphylactic reactions, ocular irritation after application of the cream to the eye lids or near the eyes, angioneurotic edema, facial edema, skin flushing associated with alcohol use, skin discoloration.

Hematology/Oncology

Lymphomas, basal cell carcinoma, malignant melanoma, squamous cell carcinoma.

Potential interactions between Elidel Cream, 1% and other drugs, including immunizations, have not been systematically evaluated. Due to low blood levels of pimecrolimus detected in some patients after topical application, systemic drug interactions are not expected, but cannot be ruled out.

The concomitant administration of known CYP3A family of inhibitors in patients with widespread and/or erythrodermic disease should be done with caution.

Some examples of such drugs are

• erythromycin,
• itraconazole,
• ketoconazole,
• fluconazole,
• calcium channel blockers and
• cimetidine.