Elidel

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Elidel

Classes

Topical Calcineurin Inhibitors

Administration
Topical Administration

A proper skin care and sun avoidance program including avoidance of the sun and protective clothing should be part of the treatment regimen.
Apply topically; may be used on all skin surfaces including the head, neck, and intertriginous areas.
Wash hands with soap and water before and after application. If treating the hands, only wash hands before application.
Do not use with occlusive dressings, as systemic exposure may be increased.

Adverse Reactions
Severe

new primary malignancy / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

constipation / Delayed / 0.4-3.7
conjunctivitis / Delayed / 0.7-3.0
erythema / Early / 0.4-2.2
dyspnea / Early / 0.6-1.8
wheezing / Rapid / 0.4-1.2
ocular infection / Delayed / 0.3-1.1
superinfection / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known

Mild

pharyngitis / Delayed / 0.7-26.5
headache / Early / 7.0-25.4
cough / Delayed / 2.4-15.8
influenza / Delayed / 3.0-13.2
fever / Early / 1.2-12.5
diarrhea / Early / 0.6-7.7
vomiting / Early / 0.6-6.6
skin irritation / Early / 0.4-6.4
folliculitis / Delayed / 0.9-6.1
pruritus / Rapid / 0.6-5.5
abdominal pain / Early / 0.3-5.5
rhinitis / Early / 0.4-4.4
nausea / Early / 0.4-4.0
sinusitis / Delayed / 0.6-3.3
epistaxis / Delayed / 0.3-3.3
dental pain / Delayed / 0.4-2.6
nasal congestion / Early / 0.6-2.6
rhinorrhea / Early / 0.4-1.9
back pain / Delayed / 0.3-1.8
acne vulgaris / Delayed / 0.3-1.5
dysmenorrhea / Delayed / 1.1-1.5
arthralgia / Delayed / 0.3-1.5
urticaria / Rapid / 0.3-1.1
skin discoloration / Delayed / Incidence not known
flushing / Rapid / Incidence not known
infection / Delayed / Incidence not known

Boxed Warning
Children, infants, neonates

Pimecrolimus cream is not for use in neonates, infants, or children < 2 years of age. However, two phase III studies have examined the use of pimecrolimus cream in pediatric patients 3 months to 2 years of age. Adverse reactions occurred more frequently in infants treated with pimecrolimus cream versus placebo. Also, although not causally established, a higher incidence of upper respiratory symptoms/infections occurred in children 3—23 months of age as compared with patients 2—14 years of age. The effect of pimecrolimus cream on the developing immune system of infants is unknown.

Immunosuppression, lymphoma, mononucleosis, new primary malignancy, skin cancer

Pimecrolimus cream should only be prescribed as directed and only after other eczema treatments have failed due to a possible risk of new primary malignancy, especially skin cancer or lymphoma. To date, there have been reports of cancers in three different animal species. The risk increased as the drug dosage increased. There have also been a small number of cancers reported in children and adults using pimecrolimus cream. The manufacturer will begin conducting research to determine the risk of cancers to humans during pimecrolimus treatment. There are no data to support the use of pimecrolimus cream in patients with immunosuppression. Increased susceptibility to infection and possible development of neoplastic disease, especially skin cancer or lymphoma, may result from immunosuppression. Patients who receive pimecrolimus cream and develop a new or changed skin lesion or lymphadenopathy should have the lesion or the etiology of their lymphadenopathy investigated due to the risk of cancer. In the absence of a clear etiology for the lymphadenopathy or in the presence of cancer or acute infectious mononucleosis, discontinuation of pimecrolimus treatment should be considered. Monitor patients to assure that the lymphadenopathy resolves.

Common Brand Names

Elidel

Dea Class

Rx

Description

Pimecrolimus (ASM 981), a derivative of ascomycin, is a topical macrolactam immunomodulator. Pimecrolimus has similar clinical effects as tacrolimus; however, they differ in therapeutic effectiveness and formulation. As opposed to topical corticosteroids, no skin atrophy is noted following pimecrolimus treatment.

Dosage And Indications
For the treatment of mild to moderate atopic dermatitis.
NOTE: Topical pimecrolimus is indicated as a second-line therapy for short-term and non-continuous chronic treatment in non-immunocompromised persons who have failed to respond adequately to other topical treatments or when those treatments are not advisable.
Topical dosage Adults

Apply a thin layer topically to the affected skin area(s) 2 times daily until symptoms resolve. If no improvement within 6 weeks, reassess diagnosis. Avoid continuous long-term use. Proactive, intermittent application of topical calcineurin inhibitors 2 to 3 times weekly to recurrent sites of disease has also been shown to be effective in reducing relapses.

Children and Adolescents 2 to 17 years

Apply a thin layer topically to the affected skin area(s) 2 times daily until symptoms resolve. If no improvement within 6 weeks, reassess diagnosis. Avoid continuous long-term use. Proactive, intermittent application of topical calcineurin inhibitors 2 to 3 times weekly to recurrent sites of disease has also been shown to be effective in reducing relapses.

Infants† and Children 1 year†

Apply a thin layer topically to the affected skin area(s) 2 times daily until symptoms resolve. Proactive, intermittent application of topical calcineurin inhibitors 2 to 3 times weekly to recurrent sites of disease has also been shown to be effective in reducing relapses.

For the treatment of vulvar lichen sclerosus†. Topical dosage Adults, Adolescents, and Children

In several case reports of female patients (ages 4 to 62 years), twice daily application of 1% pimecrolimus cream resulted in symptom resolution (i.e., pruritus, pain, and inflammation); some patients exhibited reversal of the histological changes of lichen sclerosus following 3 months of therapy. Further investigation is needed.

For the treatment of inverse psoriasis†. Topical dosage Adults

Apply topically to the affected skin area(s) twice daily. Guidelines recommend pimecrolimus for inverse (intertriginous) psoriasis for 4 to 8 weeks; long-term use may be considered.

For the treatment of dermatomyositis†. Topical dosage Adults

Apply a thin layer topically to the affected area(s) twice daily.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Ethanol: (Moderate) A flushing syndrome has been reported in patients treated with topical pimecrolimus upon ingestion of alcohol. The flushing occurred in the face or at the sites of medication application, usually within 5-15 minutes of alcohol ingestion, and lasted for an average duration of 1 hour. Roughly 3-7 percent of patients report redness and warm sensations, which sometimes result in discomfort.

How Supplied

Elidel/Pimecrolimus Topical Cream: 1%

Maximum Dosage
Adults

2 applications/day topically.

Elderly

2 applications/day topically.

Adolescents

2 applications/day topically.

Children

>= 2 years: 2 applications/day topically.

Mechanism Of Action

Mechanism of Action: Pimecrolimus inhibits calcineurin, a calcium-dependent phosphatase, by binding with high affinity to immunophilin-12 (FKBP-12), similar to tacrolimus. Immunophilins (cyclophilin and FK binding proteins) are immunosuppressant-binding proteins that are distributed in all cellular compartments and play an important role in protein activation. Calcineurin inhibition results in blockade of signal transduction by the cytosol component of the nuclear factor of activated T-cells (NF-AT), which results in a failure to activate NF-AT regulated genes. As a result, pimecrolimus inhibits T-cell activation by blocking transcription of early cytokines. At nanomolar concentrations, pimecrolimus inhibits interleukin (IL)-2, IL-4, IL-10, and interferon gamma synthesis. Pimecrolimus prevents the release of inflammatory cytokines and mediators (e.g., hexosaminidase, tryptase, and histamine) from mast cells in vitro after stimulation with antigen/IgE and inhibits the transcription of tumor necrosis factor (TNF) alpha. In atopic dermatitis, topical pimecrolimus acts to inhibit inflammation primarily by inhibiting T-cells.

Pharmacokinetics

Pimecrolimus is administered topically. In vitro, 99.5% of pimecrolimus in plasma is bound to proteins over the pimecrolimus concentration range of 2—100 ng/ml; most pimecrolimus in plasma appears to be bound to various lipoproteins. Pimecrolimus appears to be metabolized in vitro by the cytochrome P450 3A family of enzymes. No evidence of skin mediated metabolism was identified in vivo or in vitro. Following a single oral dose, about 78% of the dose was recovered in the feces as metabolites; less than 1% is excreted as unchanged drug.

Oral Route

Following oral administration, O-demethylation metabolites of pimecrolimus are seen. Following a single oral dose, about 78% of the dose was recovered in the feces as metabolites; less than 1% is excreted as unchanged drug.

Topical Route

Typically, in adults being treated for atopic dermatitis (13—62% body surface area (BSA) involvement), blood concentrations of pimecrolimus are at or below the limit of detection of the assay. If pimecrolimus is detected, the concentration is routinely < 2 ng/ml and does not accumulate with time. Absorption into cutaneous lymphatic vessels or into regional lymph nodes is unknown. No evidence of skin mediated metabolism was identified in vivo or in vitro.

Pregnancy And Lactation
Pregnancy

Pimecrolimus cream is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies of topically administered pimecrolimus in pregnant women. The experience with pimecrolimus cream when used by pregnant women is too limited to permit assessment of its safety during pregnancy.

It is not known whether pimecrolimus is excreted into breast milk. The manufacturer recommends caution when used in nursing women.  However, systemic absorption after topical use is minimal. In adult patients (n=52) treated (13—62% BSA involvement) for periods up to a year, a maximum concentration of 1.4 ng/mL was observed among those subjects with detectable serum concentrations. In the majority of patients, blood concentrations were below 0.5 ng/mL. Avoid using on the breast when breast-feeding. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.