ADVERSE REACTIONS
No phototoxicity and no photoallergenicity were detected in clinical studies with 24 and 33 normal volunteers, respectively. In human dermal safety studies, ELIDEL ® (pimecrolimus) Cream 1% did not induce contact sensitization or cumulative irritation.
In a one-year safety study in pediatric patients age 2-17 years old involving sequential use of ELIDEL Cream and a topical corticosteroid, 43% of ELIDEL patients and 68% of vehicle patients used corticosteroids during the study. Corticosteroids were used for more than 7 days by 34% of ELIDEL patients and 54% of vehicle patients. An increased incidence of impetigo, skin infection, superinfection (infected atopic dermatitis), rhinitis, and urticaria were found in the patients that had used ELIDEL Cream and topical corticosteroid sequentially as compared to ELIDEL Cream alone.
In 3 randomized, double-blind vehicle-controlled pediatric studies and one active-controlled adult study, 843 and 328 patients respectively, were treated with ELIDEL Cream. In these clinical trials, 48 (4%) of the 1,171 ELIDEL patients and 13 (3%) of 408 vehicle-treated patients 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 patients treated with ELIDEL Cream.
The following table depicts the incidence of adverse events pooled across the 2 identically designed 6-week studies with their open label extensions and the 1-year safety study for pediatric patients ages 2-17. Data from the adult active-controlled study is also included in this table. Adverse events are listed regardless of relationship to study drug.
Treatment Emergent Adverse Events (≥ 1%) in Elidel® Treatment Groups | Pediatric Patients*Vehicle-Controlled(6 weeks) | Pediatric Patients*Open-Label (20 weeks) | | Pediatric Patients*Vehicle-Controlled(1 year) | Adult ActiveComparator(1 year) |
| Elidel® Cream (N=267) N (%) | Vehicle(N=136) N (%) | Elidel® Cream (N=335) N (%) | | Elidel® Cream (N=272) N (%) | Vehicle(N=75) N (%) | Elidel® Cream(N=328)N (%) |
| At least 1 AE | 182 (68.2%) | 97 (71.3%) | 240 (72.0%) | | 230 (84.6%) | 56 (74.7%) | 256 (78.0%) |
| Infections and Infestations | | | | | | | |
| Upper Respiratory Tract Infection NOS | 38 (14.2%) | 18 (13.2%) | 65 (19.4%) | | 13 (4.8%) | 6 (8.0%) | 14 (4.3%) |
| Nasopharyngitis | 27 (10.1%) | 10 (7.4%) | 32 (19.6%) | | 72 (26.5%) | 16 (21.3%) | 25 (7.6%) |
| Skin Infection NOS | 8 (3.0%) | 9 (5.1%) | 18 (5.4%) | | 6 (2.2%) | 3 (4.0%) | 21 (6.4%) |
| Influenza | 8 (3.0%) | 1 (0.7%) | 22 (6.6%) | | 36 (13.2%) | 3 (4.0%) | 32 (9.8%) |
| Ear Infection NOS | 6 (2.2%) | 2 (1.5%) | 19 (5.7%) | | 9 (3.3%) | 1 (1.3%) | 2 (0.6%) |
| Otitis Media | 6 (2.2%) | 1 (0.7%) | 10 (3.0%) | | 8 (2.9%) | 4 (5.3%) | 2 (0.6%) |
| Impetigo | 5 (1.9%) | 3 (2.2%) | 12 (3.6%) | | 11 (4.0%) | 4 (5.3%) | 8 (2.4%) |
| Bacterial Infection | 4 (1.5%) | 3 (2.2%) | 4 (1.2%) | | 3 (1.1%) | 0 | 6 (1.8%) |
| Folliculitis | 3 (1.1%) | 1 (0.7%) | 3 (0.9%) | | 6 (2.2%) | 3 (4.0%) | 20 (6.1%) |
| Sinusitis | 3 (1.1%) | 1 (0.7%) | 11 (3.3%) | | 6 (2.2%) | 1 (1.3%) | 2 (0.6%) |
| Pneumonia NOS | 3 (1.1%) | 1 (0.7%) | 5 (1.5%) | | 0 | 1 (1.3%) | 1 (0.3%) |
| Pharyngitis NOS | 2 (0.7%) | 2 (1.5%) | 3 (0.9%) | | 22 (8.1%) | 2 (2.7%) | 3 (0.9%) |
| Pharyngitis Streptococcal | 2 (0.7%) | 2 (1.5%) | 10 (3.0%) | | 0 | <1% | 0 |
| Molluscum Contagiosum | 2 (0.7%) | 0 | 4 (1.2%) | | 5 (1.8%) | 0 | 0 |
| Staphylococcal Infection | 1 (0.4%) | 5 (3.7%) | 7 (2.1%) | | 0 | <1% | 3 (0.9%) |
| Bronchitis NOS | 1 (0.4%) | 3 (2.2%) | 4 (1.2%) | | 29 (10.7%) | 6 (8.0%) | 8 (2.4%) |
| Herpes Simplex | 1 (0.4%) | 0 | 4 (1.2%) | | 9 (3.3%) | 2 (2.7%) | 13 (4.0%) |
| Tonsillitis NOS | 1 (0.4%) | 0 | 3 (0.9%) | | 17 (6.3%) | 0 | 2 (0.6%) |
| Viral Infection NOS | 2 (0.7%) | 1 (0.7%) | 1 (0.3%) | | 18 (6.6%) | 1 (1.3%) | 0 |
| Gastroenteritis NOS | 0 | 3 (2.2%) | 2 (0.6%) | | 20 (7.4%) | 2 (2.7%) | 6 (1.8%) |
| Chickenpox | 2 (0.7%) | 0 | 3 (0.9%) | | 8 (2.9%) | 3 (4.0%) | 1 (0.3%) |
| Skin Papilloma | 1 (0.4%) | 0 | 2 (0.6%) | | 9 (3.3%) | <1% | 0 |
| Tonsillitis Acute NOS | 0 | 0 | 0 | | 7 (2.6%) | 0 | 0 |
| Upper Respiratory Tract Infection Viral NOS | 1 (0.4%) | 0 | 3 (0.9%) | | 4 (1.5%) | 0 | 1 (0.3%) |
| Herpes Simplex Dermatitis | 0 | 0 | 1 (0.3%) | | 4 (1.5%) | 0 | 2 (0.6%) |
| Bronchitis Acute NOS | 0 | 0 | 0 | | 4 (1.5%) | 0 | 0 |
| Eye Infection NOS | 0 | 0 | 0 | | 3 (1.1%) | <1% | 1 (0.3%) |
| General Disorders and Administration Site Conditions | | | | | | | |
| Application Site Burning | 28 (10.4%) | 17 (12.5%) | 5 (1.5%) | | 23 (8.5%) | 5 (6.7%) | 85 (25.9%) |
| Pyrexia | 20 (7.5%) | 12 (8.8%) | 41 (12.2%) | | 34 (12.5%) | 4 (5.3%) | 4 (1.2%) |
| Application Site Reaction NOS | 8 (3.0%) | 7 (5.1%) | 7 (2.1%) | | 9 (3.3%) | 2 (2.7%) | 48 (14.6%) |
| Application Site Irritation | 8 (3.0%) | 8 (5.9%) | 3 (0.9%) | | 1 (0.4%) | 3 (4.0%) | 21 (6.4%) |
| Influenza Like Illness | 1 (0.4%) | 0 | 2 (0.6%) | | 5 (1.8%) | 2 (2.7%) | 6 (1.8%) |
| Application Site Erythema | 1 (0.4%) | 0 | 0 | | 6 (2.2%) | 0 | 7 (2.1%) |
| Application Site Pruritus | 3 (1.1%) | 2 (1.5%) | 2 (0.6%) | | 5 (1.8%) | 0 | 18 (5.5%) |
| Respiratory, Thoracic and Mediastinal Disorders | | | | | | | |
| Cough | 31 (11.6%) | 11 (8.1%) | 31 (9.3%) | | 43 (15.8%) | 8 (10.7%) | 8 (2.4%) |
| Nasal Congestion | 7 (2.6%) | 2 (1.5%) | 6 (1.8%) | | 4 (1.5%) | 1 (1.3%) | 2 (0.6%) |
| Rhinorrhea | 5 (1.9%) | 1 (0.7%) | 3 (0.9%) | | 1 (0.4%) | 1 (1.3%) | 0 |
| Asthma Aggravated | 4 (1.5%) | 3 (2.2%) | 13 (3.9%) | | 3 (1.1%) | 1 (1.3%) | 0 |
| Sinus Congestion | 3 (1.1%) | 1 (0.7%) | 2 (0.6%) | | <1% | <1% | 3 (0.9%) |
| Rhinitis | 1 (0.4%) | 0 | 5 (1.5%) | | 12 (4.4%) | 5 (6.7%) | 7 (2.1%) |
| Wheezing | 1 (0.4%) | 1 (0.7%) | 4 (1.2%) | | 2 (0.7%) | <1% | 0 |
| Asthma NOS | 2 (0.7%) | 1 (0.7%) | 11 (3.3%) | | 10 (3.7%) | 2 (2.7%) | 8 (2.4%) |
| Epistaxis | 0 | 1 (0.7%) | 0 | | 9 (3.3%) | 1 (1.3%) | 1 (0.3%) |
| Dyspnea NOS | 0 | 0 | 0 | | 5 (1.8%) | 1 (1.3%) | 2 (0.6%) |
| Gastrointestinal Disorders | | | | | | | |
| Abdominal Pain Upper | 11 (4.1%) | 6 (4.4%) | 10 (3.0%) | | 15 (5.5%) | 5 (6.7%) | 1 (0.3%) |
| Sore Throat | 9 (3.4%) | 5 (3.7%) | 15 (5.4%) | | 22 (8.1%) | 4 (5.3%) | 12 (3.7%) |
| Vomiting NOS | 8 (3.0%) | 6 (4.4%) | 14 (4.2%) | | 18 (6.6%) | 6 (8.0%) | 2 (0.6%) |
| Diarrhea NOS | 3 (1.1%) | 1 (0.7%) | 2 (0.6%) | | 21 (7.7%) | 4 (5.3%) | 7 (2.1%) |
| Nausea | 1 (0.4%) | 3 (2.2%) | 4 (1.2%) | | 11 (4.0%) | 5 (6.7%) | 6 (1.8%) |
| Abdominal Pain NOS | 1 (0.4%) | 1 (0.7%) | 5 (1.5%) | | 12 (4.4%) | 3 (4.0%) | 1 (0.3%) |
| Toothache | 1 (0.4%) | 1 (0.7%) | 2 (0.6%) | | 7 (2.6%) | 1 (1.3%) | 2 (0.6%) |
| Constipation | 1 (0.4%) | 0 | 2 (0.6%) | | 10 (3.7%) | <1% | 0 |
| Loose Stools | 0 | 1 (0.7%) | 4 (1.2%) | | <1% | <1% | 0 |
| Reproductive System and Breast Disorders | | | | | | | |
| Dysmenorrhea | 3 (1.1%) | 0 | 5 (1.5%) | | 3 (1.1%) | 1 (1.3%) | 4 (1.2%) |
| Eye Disorders | | | | | | | |
| Conjunctivitis NEC | 2 (0.7%) | 1 (0.7%) | 7 (2.1%) | | 6 (2.2%) | 3 (4.0%) | 10 (3.0%) |
| Skin & Subcutaneous Tissue Disorders | | | | | | | |
| Urticaria | 3 (1.1%) | 0 | 1 (0.3%) | | 1 (0.4%) | <1% | 3 (0.9%) |
| Acne NOS | 0 | 1 (0.7%) | 1 (0.3%) | | 4 (1.5%) | <1% | 6 (1.8%) |
| Immune System Disorders | | | | | | | |
| Hypersensitivity NOS | 11 (4.1%) | 6 (4.4%) | 16 (4.8%) | | 14 (5.1%) | 1 (1.3%) | 11 (3.4%) |
| Injury and Poisoning | | | | | | | |
| Accident NOS | 3 (1.1%) | 1 (0.7%) | 1 (0.3%) | | <1% | 1 (1.3%) | 0 |
| Laceration | 2 (0.7%) | 1 (0.7%) | 5 (1.5%) | | <1% | <1% | 0 |
| Musculoskeletal, Connective Tissue and Bone Disorders | | | | | | | |
| Back Pain | 1 (0.4%) | 2 (1.5%) | 1 (0.3%) | | <1% | 0 | 6 (1.8%) |
| Arthralgias | 0 | 0 | 1 (0.3%) | | 3 (1.1%) | 1 (1.3%) | 5 (1.5%) |
| Ear and Labyrinth Disorders | | | | | | | |
| Earache | 2 (0.7%) | 1 (0.7%) | 0 | | 8 (2.9%) | 2 (2.7%) | 0 |
| Nervous System Disorders | | | | | | | |
| Headache | 37 (13.9%) | 12 (8.8%) | 38 (11.3%) | | 69 (25.4%) | 12 (16.0%) | 23 (7.0%) |
*Ages 2-17 years
Two cases of septic arthritis have been reported in infants less than one year of age in clinical trials conducted with ELIDEL Cream (n = 2,443). Causality has not been established.
POST-MARKETING EVENTS
The following adverse reactions have been reported in patients using ELIDEL Cream. 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
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