ELIDEL SIDE EFFECTS
- Generic Name: pimecrolimus cream
- Brand Name: Elidel
- Drug Class: Immunosuppressive Agents, Topical, Calcineurin Inhibitors
SIDE EFFECTS
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
| Pediatric Subjects* Vehicle-Controlled (6 weeks) | Pediatric Subjects* Open-Label (20 weeks) | Pediatric Subjects*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(68.20%) | 97(71.30%) | 240 (72.0%) | 230 (84.6%) | 56(74.70%) | 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, 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.
SRC: NLM .