Cream, 1% Topical Calcineurin Inhibitor Novartis Pharmaceuticals Canada Inc. Dorval, Quebec, H9S 1A9
Date of Revision: August 6, 2008 is a registered trademark
Table of Contents
INDICATIONS AND CLINICAL USE 3 CONTRAINDICATIONS 3 WARNINGS AND PRECAUTIONS 3 ADVERSE REACTIONS 6 DRUG INTERACTIONS 11 DOSAGE AND ADMINISTRATION 11 OVERDOSAGE 12 ACTION AND CLINICAL PHARMACOLOGY 12 STORAGE AND STABILITY 13 DOSAGE FORMS, COMPOSITION AND PACKAGING 13
PHARMACEUTICAL INFORMATION 14 CLINICAL TRIALS 15 DETAILED PHARMACOLOGY 16 TOXICOLOGY 18 REFERENCES 22
PrELIDEL * (Pimecrolimus)
| Route of Administration | Dosage Form / Strength | Clinically Relevant Nonmedicinal Ingredients |
| Topic | Cream 1% | Benzyl alcohol For a complete listing see Dosage Forms, Composition and Packaging section. |
ELIDEL * (pimecrolimus) cream 1% is indicated as a second-line therapy for short-term and intermittent long-term therapy of mild to moderate atopic dermatitis in non-immunocompromised patients 2 years of age and older, in whom the use of alternative, conventional therapies is deemed inadvisable because of potential risks, or in the treatment of patients who are not adequately responsive to or intolerant of alternative, conventional therapies. For additional safety information, please refer to WARNINGS AND PRECAUTIONS section.
ELIDEL * (pimecrolimus) Cream, 1% is contraindicated in individuals who have known or suspected hypersensitivity to pimecrolimus or any of the components of the cream.
Long-term safety of topical calcineurin inhibitors has not been established. Although a causal relationship has not been established, rare cases of skin malignancy and lymphoma have been reported in patients treated with topical calcineurin inhibitors, including ELIDEL * Cream 1%. Therefore:
Continuous long-term use of ELIDEL * Cream 1% should be avoided, and application limited to areas of involvement with atopic dermatitis.
ELIDEL * Cream 1% is not indicated in children less than 2 years of age.
General
ELIDEL * (pimecrolimus) Cream, 1% should not be applied to areas of active cutaneous viral infections. ELIDEL * has not been evaluated for its efficacy and safety in the treatment of clinically infected atopic dermatitis. Before commencing treatment with ELIDEL *, clinical infections at treatment sites should be cleared. While patients with atopic dermatitis are predisposed to surface infections including eczema herpeticum (Kaposi's varicelliform eruption) treatment with ELIDEL * may be associated with an increased risk of varicella zoster virus infection (chickenpox or shingles), herpes simplex virus infection, or eczema herpeticum. In presence of these skin infections, ELIDEL * treatment at the site of infection should be discontinued until the viral infection is cleared. Although patients treated with ELIDEL * experienced overall a lower incidence of bacterial skin infections as compared to patients treated with the vehicle, patients with severe atopic dermatitis may have an increased risk of skin bacterial infections (impetigo) during treatment with ELIDEL *. Cases of lymphadenopathy (0.9%) were reported in patients treated with ELIDEL *. These cases of lymphadenopathy were usually related to infections and noted to resolve upon appropriate antibiotic therapy. However, in the absence of clear etiology for the lymphadenopathy, or in the presence of acute infectious mononucleosis, discontinuation of ELIDEL * should be considered. Patients who developed lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves.
Carcinogenesis
In clinical studies, cases of skin papilloma or warts (1%) were observed in pediatric patients treated with ELIDEL *. In cases where patients have worsening of skin papillomas or do not respond to conventional therapy, discontinuation of ELIDEL * should be considered until complete resolution of the warts is achieved. Animal photocarcinogenicity study: Despite the absence of observed phototoxicity in humans, ELIDEL * cream and its vehicle shortened the time to skin papilloma formation. It is prudent for patients to minimize or avoid exposure to natural or artificial sunlight (see Carcinogenesis, Mutagenesis, Impairment of Fertility). The enhancement of ultraviolet carcinogenicity is not necessarily dependent on phototoxic mechanisms. Animal studies of monkey and mice using pimecrolimus administered at high and sustained doses were associated with lymphoma formation. Chronic topical dosing of ELIDEL * Cream 1% or vehicle alone in hairless mice with concurrent exposure to UV radiation decreased the median time to onset of skin tumor formation. (see Carcinogesis, Mutagenesis, Impairment of Fertility).
Immune
There are no data to support use of ELIDEL * in immunocompromised patients.
Ophthalmologic
ELIDEL * (pimecrolimus) Cream, 1% is not for ophthalmic use.
Skin
ELIDEL * cream should not be used in patients with Netherton's syndrome due to the potential for increased systemic absorption of pimecrolimus. The use of ELIDEL * may cause local symptoms such as skin burning, which are mostly mild and transient. If the application site reaction is severe, the risk-benefit of treatment with ELIDEL * should be considered.
Special Populations
Pregnant Women:
There are no adequate and well-controlled studies in pregnant women. Studies in rats and rabbits, by dermal and oral administration gave no evidence of a teratogenic potential of pimecrolimus. Because animal reproduction studies are not always predictive of human response, this drug should be used only if clearly needed during pregnancy.
It is not known whether this drug is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from pimecrolimus, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
:
ELIDEL * may be used in pediatric patients 2 years of age and older. ELIDEL * is not recommended for use in pediatric patients below the age of 2 years. Studies have been conducted in pediatric patients below 2 years of age (3 months to 23 months). Certain adverse event incidences, including pyrexia, URI, cough, rhinitis, viral rash, and wheezing, were found to be higher in patients treated with ELIDEL * in comparison with patients treated with vehicle. The effects of ELIDEL * on the developing immune system in infants are unknown.
:
Clinical studies of ELIDEL * did not include sufficient numbers of subjects aged 65 and older to establish efficacy and safety of the drug in geriatric patients.
Information to be provided to the Patient/Guardian
Patients using ELIDEL * should receive the following information and instructions: Patients should use ELIDEL * as directed by the physician. ELIDEL * is for external use only. Patients should wash their hands after application if hands are not an area for treatment. Care should be taken to avoid contact with nose, eyes and mouth. If accidentally applied to these areas, the cream should be thoroughly wiped off and rinsed off with water.
Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using ELIDEL *.
Patients should not use this medication for any disorder other than that for which it was prescribed.
Patients should report any signs of adverse reactions to their physician.
Before applying ELIDEL * after a bath or shower, be sure your skin is completely dry.
Therapy should be discontinued after signs and symptoms of atopic dermatitis have resolved.
If no improvement is seen following 3 weeks of treatment, or in case of disease exacerbation, ELIDEL * therapy should be discontinued and patients should consult their physicians.
Adverse Drug Reaction Overview
In human dermal safety studies, ELIDEL * did not induce contact sensitization, phototoxicity, or photoallergy, nor did it show any cumulative irritation. ELIDEL * did not elicit skin atrophy compared to topical corticosteroid use. 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 1%. In these clinical trials, 48 (4%) of the 1171 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.
Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The table below 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 control 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
Pediatric Patients * Vehicle-Controlled (1 year)
Adult Active Comparator (1 year)
| At least 1 AE Infections and Infestatio Upper Respiratory Tract Infection NOS Nasopharyngitis Skin Infection NOS Influenza Ear Infection NOS Otitis Media Impetigo | 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 (%) |
| 182 | 97 | 240 | 230 | 56 | 256 | |
| (68.2%) | (71.3%) | (72.0%) | (84.6%) | (74.7%) | (78.0%) | |
| 38 | 18 | 65 | 13 | 6 | 14 | |
| (14.2%) | (13.2%) | (19.4%) | (4.8%) | (8.0%) | (4.3%) | |
| 27 | 10 | 32 | 72 | 16 | 25 | |
| (10.1%) | (7.4%) | (19.6%) | (26.5%) | (21.3%) | (7.6%) | |
| 8 | 9 | 18 | 6 | 3 | 21 | |
| (3.0%) | (5.1%) | (5.4%) | (2.2%) | (4.0%) | (6.4%) | |
| 8 | 1 | 22 | 36 | 3 | 32 | |
| (3.0%) | (0.7%) | (6.6%) | (13.2%) | (4.0%) | (9.8%) | |
| 6 | 2 | 19 | 9 | 1 | 2 | |
| (2.2%) | (1.5%) | (5.7%) | (3.3%) | (1.3%) | (0.6%) | |
| 6 | 1 | 10 | 8 | 4 | 2 | |
| (2.2%) | (0.7%) | (3.0%) | (2.9%) | (5.3%) | (0.6%) | |
| 5 | 3 | 12 | 11 | 4 | 8 | |
| (1.9%) | (2.2%) | (3.6%) | (4.0%) | (5.3%) | (2.4%) | |
| Bacterial Infection | 4 (1.5%) | 3 (2.2%) | 4 (1.2%) | 3 (1.1%) | 0 | 6 (1.8%) |
| Folliculitis | 3 | 1 | 3 | 6 | 3 | 20 |
| (1.1%) | (0.7%) | (0.9%) | (2.2%) | (4.0%) | (6.1%) | |
| Sinusitis | 3 | 1 | 11 | 6 | 1 | 2 |
| (1.1%) | (0.7%) | (3.3%) | (2.2%) | (1.3%) | (0.6%) | |
| Pneumonia NOS | 3 (1.1%) | 1 (0.7%) | 5 (1.5%) | 0 | 1 (1.3%) | 1 (0.3%) |
(20 weeks)
ns
Pharyngitis NOS 2
| Pharyngitis Streptococcal 2 2 10 0 | <1% | 0 |
| (0.7%) (1.5%) (3.0%) Molluscum Contagiosum 2 0 4 5 0 0 | ||
| (0.7%) (1.2%) (1.8%) | ||
(1.5%)
(0.9%)
(8.1%)
(2.7%)
(0.9%)
Staphylococcal Infection 1
(3.7%)
(2.1%)
0 <1% 3
Bronchitis NOS 1
(2.2%)
(1.2%)
(10.7%)
(8.0%)
(2.4%)
Herpes Simplex 1
(3.3%)
(2.7%)
(4.0%)
Tonsillitis NOS 1
(6.3%)
(0.6%)
Viral Infection NOS 2
(0.7%)
(0.3%)
(6.6%)
(1.3%) 0
Pediatric Patients * Vehicle-Controlled (6 weeks)
Pediatric Patients Open Label
Pediatric Patients * Vehicle-Controlled (1 year)
Adult Active Comparator (1 year)
(20 weeks)
Cream (N=267)
Vehicle
(N=136)
ELIDEL *
Cream (N=335)
ELIDEL *
Cream (N=272)
Vehicle
(N=75)
ELIDEL *
Cream (N=328)
N (%) N (%) N (%) N (%) N (%) N (%)
| 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
(0.4%) 0
(0.9%)
(1.5%) 0
(0.3%)
Herpes Simplex Dermatitis 0 0 1
(1.5%)
(0.6%)
Bronchitis Acute NOS 0 0 0 4
| 0 | 0 | 0 3 <1% (1.1%) | |
| 28 | 17 | 5 2 | 3 5 |
| (10.4%) | (12.5%) | (1.5%) (8.5%) (6.7%) | |
| 20 | 12 | 41 3 | 4 4 |
| (7.5%) | (8.8%) | (12.2%) (12. | 5%) (5.3%) |
| 8 | 7 | 7 9 2 | |
| (3.0%) | (5.1%) | (2.1%) (3.3%) (2.7%) | |
| 8 | 8 | 3 1 3 | |
| (3.0%) | (5.9%) | (0.9%) (0.4%) (4.0%) | |
| 1 | 0 | 2 5 2 | |
| (0.4%) | (0.6%) (1.8%) (2.7%) | ||
Eye Infection NOS
General Disorders and Administration Site Conditions
Application Site Burning
Pyrexia
Application Site Irritation NOS
Application Site Irritation
Influenza Like Illness
0 0
(0.3%)
(25.9%)
(1.2%)
(14.6%)
(6.4%)
(1.8%)
Application Site Erythema 1
0 0 6
(2.1%) | |||
|---|---|---|---|
| Application Site Prur Respiratory, Thora Mediastinal Disord Cough Nasal Congestion Rhinorrhea Asthma Aggravated Sinus Congestion | itus 3 (1.1%) cic and | (1.5%) | (0.6%) |
| ers 31 | 11 | 31 | |
| (11.6%) | (8.1%) | (9.3%) | |
| 7 | 2 | 6 | |
| (2.6%) | (1.5%) | (1.8%) | |
| 5 | 1 | 3 | |
| (1.9%) | (0.7%) | (0.9%) | |
| 4 | 3 | 13 | |
| (1.5%) | (2.2%) | (3.9%) | |
| 3 | 1 | 2 | |
| (1.1%) | (0.7%) | (0.6%) | |
| Rhinitis | 1 (0.4%) | 0 | 5 (1.5%) |
2 2 5
(5.5%)
(10.7%)
(1.3%)
(1.3%)
(1.3%)
(2.4%)
(0.6%)
(6.7%)
(2.1%)
Pediatric Patients * Vehicle-Controlled (6 weeks)
Pediatric Patients Open Label
Pediatric Patients * Vehicle-Controlled (1 year)
Adult Active Comparator (1 year)
(20 weeks)
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 (%)
Wheezing 1
(0.7%)
(1.2%)
(0.7%)
<1% 0
Asthma NOS 2
(0.7%)
(3.3%)
(3.7%)
(2.7%)
(2.4%)
Epistaxis 0 1
(3.3%)
(1.3%)
(0.3%)
Dyspnea NOS 0 0 0 5
(1.3%)
(0.6%)
| Abdominal Pain Upper 11 6 10 15 (4.1%) (4.4%) (3.0%) (5.5%) Sore Throat 9 5 15 22 (3.4%) (3.7%) (5.4%) (8.1%) Vomiting NOS 8 6 14 18 (3.0%) (4.4%) (4.2%) (6.6%) Diarrhea NOS 3 1 2 21 (1.1%) (0.7%) (0.6%) (7.7%) Nau sea 1 3 4 11 (0.4%) (2.2%) (1.2%) (4.0%) Abdominal Pain NOS 1 1 5 12 (0.4%) (0.7%) (1.5%) (4.4%) Toothache 1 1 2 7 (0.4%) (0.7%) (0.6%) (2.6%) | 5 | 1 | |||
| (6.7%) | (0.3%) | ||||
| 4 | 12 | ||||
| (5.3%) | (3.7%) | ||||
| 6 | 2 | ||||
| (8.0%) | (0.6%) | ||||
| 4 | 7 | ||||
| (5.3%) | (2.1%) | ||||
| 5 | 6 | ||||
| (6.7%) | (1.8%) | ||||
| 3 | 1 | ||||
| (4.0%) | (0.3%) | ||||
| 1 | 2 | ||||
| (1.3%) | (0.6%) | ||||
| Constipation | 1 (0.4%) | 0 2 10 (0.6%) (3.7%) | <1% | 0 | |
| Loose Stools | 0 | 1 (0.7%) (1 | 4 <1% .2%) | <1% | 0 |
| Reproductive System and Breast Disorders | |||||
| Dysmenorrhea | 3 | 0 | 5 3 | 1 | 4 |
| (1.1%) | (1.5%) (1.1%) | (1.3%) | (1.2%) | ||
Gastrointestinal Disorders
Eye Disorders
Conjunctivitis NEC 2
(0.7%)
(2.1%)
(2.2%)
(4.0%)
(3.0%)
Skin & Subcutaneous Tissue Disorders
Urticaria 3
(0.3%)
(0.4%)
<1% 3
(0.9%)
Acne NOS 0 1
(0.3%)
(1.5%)
<1% 6
(1.8%)
Immune System Disorders
Hypersensitivity NOS 11
(4.4%)
(4.8%)
(5.1%)
(1.3%)
(3.4%)
Injury and Poisoning
Pediatric Patients * Vehicle-Controlled (6 weeks)
Pediatric Patients Open Label
Pediatric Patients * Vehicle-Controlled (1 year)
Adult Active Comparator (1 year)
(20 weeks)
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 (%)
Accident NOS 3
(0.7%)
(0.3%)
<1% 1 0
(1.3%)
Laceration 2 1
<1% <1% 0
(0.7%) (0.7%) (1.5%)
Musculoskeletal, Connective
Tissue and Bone Disorders
Back Pain 1
(1.5%)
(0.3%)
<1% 0 6
Arthralgias 0 0 1
(1.1%)
(1.3%)
(1.5%)
Ear and Labyrinth Disorders
Earache 2
(0.7%)
(2.7%) 0
Nervous System Disorders
Headache 37
(8.8%)
(11.3%)
(25.4%)
(16.0%)
(7.0%)
*Ages 2-17 years
NOS = not otherwise specified
A clinical study showed that the incidence of overall viral skin infections were significantly increased in the ELIDEL * treated group compared to the vehicle control group (12.4% vs. 6.3%, p=0.038). In clinical trials, there were two cases of cancer (squamous cell carcinoma of the skin and colon carcinoma) out of 19,000 patients on ELIDEL *, and 5 cases of cancer (gastric cancer, melanoma, malignant histiocytosis, leukemia, and thyroid cancer) out of 4,000 patients given the control, 4 out of 5 of which were on topical corticosteroids. Clinical studies show no evidence of an increased risk of cancer.
Post-Marketing Adverse Events
The following adverse reactions have been reported in patients also having used 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
Alcohol intolerance has been rarely (<1 out of 1,000) reported in patients treated with ELIDEL * 1% cream. In most cases, flushing, rash, burning, itching or swelling occurred shortly after the intake of alcohol. Allergic reactions (e.g. rash, urticaria, angioedema) and skin discoloration (e.g. hypopigmentation, hyperpigmentation) have been rarely reported in patients treated with ELIDEL *. Very rarely, anaphylactic reactions, including erythroderma and anaphylactic shock, have been reported.
Hematology/Oncology: Isolated cases of malignant neoplasms were reported from post-marketing surveillance for patients also having used ELIDEL * Cream 1%. The malignancies included T- and B-cell type lymphomas, skin neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma), and malignancies of various organs. A causal relationship between the use of ELIDEL * Cream 1% and the reported cases has not been established. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Overview
Potential interactions between ELIDEL * and other drugs, including immunizations, have not been systematically evaluated. Although very low blood levels of pimecrolimus are detected in a minority of patients after topical application, the concomitant administration of known CYP3A inhibitors in patients with wide spread and/or erythrodermic diseases should be done with caution. Some examples of these drugs are: erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blocker and cimetidine.
Recommended Dose and Dosage Adjustment
Apply a thin layer of ELIDEL * (pimecrolimus) Cream, 1% to sufficiently cover the affected skin area twice daily. ELIDEL * may be used on all skin surfaces, including the head, neck, and intertriginous areas. ELIDEL * Cream should be used for short or long intermittent periods of treatment. Therapy should be stopped upon clearance of the signs and symptoms of atopic dermatitis (e.g. pruritus, inflammation and erythema). Treatment should be discontinued if resolution of disease occurs. If no improvement occurs after 3 weeks of treatment, or in case of disease exacerbation, ELIDEL * therapy should be discontinued and patients should consult their physicians. The use of ELIDEL * under occlusion has not been studied, therefore occlusive dressings are not recommended.
There has been no experience of overdose with ELIDEL * (pimecrolimus) Cream, 1%. No incidents of accidental ingestion have been reported.
Mechanism of Action
The exact mechanism of action of pimecrolimus in atopic dermatitis is not known. However, it has been demonstrated that pimecrolimus binds with high affinity to macrophilin-12 and inhibits the calcium-dependent phosphatase, calcineurin. As a consequence, it inhibits T cell activation by blocking the transcription of early cytokines. In particular, pimecrolimus inhibits at nanomolar concentrations Interleukin-2 and interferon gamma (Th1-type) and Interleukin-4 and Interleukin-10 (Th2-type) cytokine synthesis in human T cells. In addition, pimecrolimus prevents the release of cytokines and pro-inflammatory mediators from mast cells in vitro after stimulation by antigen/IgE. Pimecrolimus does not affect the growth of, or IL-8 release from, keratinocyte, fibroblast, and endothelial cell lines.
Pharmacokinetics
Systemic exposure to pimecrolimus was investigated in 58 pediatric patients aged 3 months to 4 years and 8 to 14 years. For these patients, atopic dermatitis (AD) lesions involving 10%-92% of the total body surface area were treated with ELIDEL * (pimecrolimus) Cream, 1% twice daily for 3 weeks. Blood concentrations measured in the youngest patients aged 3 to 23 months were consistently low, ranging from below the assay limit of quantitation (LoQ: 0.1 ng/mL) to 2.6 ng/mL. In earlier studies, blood concentrations in pediatric patients 8 months to 14 years of age were also low, ranging from below the LoQ (0.5 ng/mL) to 2.0 ng/mL. Overall, the majority of concentrations measured was below the limit of quantitation and there was no evidence of higher blood concentrations in patients even with a high proportion of their total body surface area (%TBSA) under treatment (>70% TBSA).
The range of blood concentrations measured in adult AD patients ( 18 years of age) was similar to that in pediatric patients. The highest blood level of pimecrolimus measured in adults was 1.4 ng/mL. In 8 adult AD patients the AUC(0-12h) values ranged from 2.5 to 11.4 ng.h/mL. In 40 adult patients treated for up to 1 year with ELIDEL *, blood concentrations of pimecrolimus were low. A maximum blood concentration of 0.8 ng/mL was observed in only 2 patients in week 6 of treatment. There was no increase of blood concentration over time in any patient during the 12 months of treatment. In 13 adult patients with hand dermatitis treated with ELIDEL * twice daily for 3 weeks (palmar and dorsal surfaces of hands treated, overnight occlusion), the maximum blood concentration of pimecrolimus was 0.91 ng/mL.
In man, the fate of pimecrolimus in the body following topical application could not be determined due to low systemic absorption and low resultant blood concentrations of pimecrolimus. No drug metabolism was observed in human skin in vitro. After single oral administration in healthy subjects, unchanged pimecrolimus was the major drug-related component in blood and there were numerous minor metabolites of moderate polarity that appeared to be products of O-demethylations and oxygenation. Drug related radioactivity was excreted principally via the feces (78.4%) and only a small fraction (2.5%) was recovered in urine. Total mean recovery of radioactivity was 80.9%. Parent compound was not detected in urine and less than 1% of radioactivity in feces was accounted for by unchanged pimecrolimus.
Store at room temperature (15oC-30oC). Do not freeze. The in-use (consumption) period of the tube, following piercing of the aluminum membrane, is 12 months.
ELIDEL * (pimecrolimus) Cream, 1% is available in tubes of 30, 60 and 100 grams.
Composition:
Each gram of ELIDEL * Cream, 1% contains 10 mg of pimecrolimus.
Inactive Ingredients
: benzyl alcohol, cetyl alcohol, citric acid, mono- and di-glycerides, oleyl alcohol, propylene glycol, sodium cetostearyl sulphate, sodium hydroxide, stearyl alcohol, triglycerides, and water.