Version July 2023
Long-term safety of topical calcineurin inhibitors has not been established. Continuous long-term use of topical calcineurin inhibitors, including pimecrolimus, in any age group should be avoided, and application limited to areas of involvement with atopic dermatitis.
Although a causal relationship has not been established, rare cases of malignancy (eg, skin malignancy, lymphoma) have been reported in patients treated with topical calcineurin inhibitors including pimecrolimus.
Pimecrolimus is not indicated for use in children younger than 2 years.
Atopic dermatitis (mild to moderate): Topical: Apply thin layer to affected area twice daily. Note: Limit application to involved areas. Discontinue use when symptoms have resolved; re-evaluate if symptoms persist >6 weeks.
Oral lichen planus (off-label use): Topical: Apply twice daily for 1 month (Passeron 2007; Swift 2005; Volz 2008).
Psoriasis (intertriginous and facial) (off-label use): Topical: Apply twice daily (AAD-NPF [Elmets 2021]; Gribetz 2004).
Vitiligo (off-label use): Topical: Apply twice daily for 6 months. Treatment beyond 12 months may be useful; long-term safety has not been established. (Esfandiarpour 2009; Stinco 2009; Taieb 2013).
(For additional information see "Pimecrolimus: Pediatric drug information")
Atopic dermatitis (mild-moderate): Children ≥2 years and Adolescents: Topical: Apply a thin layer to affected area twice daily; limit application to affected areas only; discontinue therapy when symptoms have resolved; re-evaluate patient if symptoms persist >6 weeks.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, External:
Elidel: 1% (30 g, 60 g, 100 g) [contains benzyl alcohol, cetyl alcohol, propylene glycol]
Generic: 1% (30 g, 60 g, 100 g)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, External:
Elidel: 1% (15 g, 30 g, 60 g, 100 g) [contains benzyl alcohol, cetyl alcohol, propylene glycol]
An FDA-approved patient medication guide, which is available with the product information and at https://www.fda.gov/media/73430/download, must be dispensed with this medication.
Topical: Apply a thin layer to affected skin. Limit application to areas of involvement. Do not use with occlusive dressings. Burning at the application site is most common in first few days but improves over time. Discontinue use when symptoms have resolved; re-evaluate if symptoms persist >6 weeks. Moisturizers may be applied after use of pimecrolimus cream. Wash hands before and after use.
Oral lichen planus (off-label use): Apply to affected oral mucosa, cover with a thin layer of gauze to delay dilution with saliva (Volz 2008). Eating, drinking, or chewing gum was not allowed for 30 minutes after application (Passeron 2007).
Topical: Apply a thin layer of cream over affected area; limit application to areas of involvement; do not use with occlusive dressings. Burning at the application sites is common in the first few days of treatment and improves as atopic dermatitis improves. Discontinue use when symptoms have resolved. Avoid contact with eyes, nose, mouth and with cut, scraped, or infected skin areas. Wash hands with soap and water prior to and after cream application. If applying cream after a bath or shower, make sure skin is dry. Moisturizers may be applied after use of pimecrolimus cream.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Pimecrolimus may cause carcinogenicity and has a structural or toxicity profile similar to existing hazardous agents. Assess risk to determine appropriate containment strategy (USP-NF 2017).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, and (if liquid that could splash) eye/face protection for administration of a topical product; if there is potential for inhalation, respiratory protections is recommended (NIOSH 2016).
Atopic dermatitis: Second-line therapy for short-term and noncontinuous long-term treatment of mild to moderate atopic dermatitis in nonimmunocompromised patients 2 years and older who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable.
Oral lichen planus; Psoriasis (intertriginous and facial); Rosacea; Vitiligo
Pimecrolimus may be confused with tacrolimus
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (children and adolescents 11% to 25%; adults 7%), fever (children and adolescents 13%; adults 1%)
Infection: Influenza (3% to 13%)
Local: Local burning (adults 26%; children and adolescents 2% to 8%; tends to resolve/improve as lesions resolve), application site reaction (adults 15%; children and adolescents 2%)
Respiratory: Nasopharyngitis (infants, children, and adolescents 10% to 27%; adults 8%), upper respiratory tract infection (children and adolescents 14% to 19%; adults 4%), cough (children and adolescents 9% to 16%; adults 2%), bronchitis (children and adolescents ≤11%; adults ≤2%)
1% to 10%:
Dermatologic: Folliculitis (adults 6%; children and adolescents 1%), skin infection (5% to 6%), impetigo (4%), warts (children and adolescents ≤3%), acne vulgaris (≤2%), herpes simplex dermatitis (≤2%), molluscum contagiosum (children and adolescents ≤2%), urticaria (≤1%)
Gastrointestinal: Diarrhea (children and adolescents 1% to 8%; adults ≤2%), gastroenteritis (children and adolescents ≤7%; adults 2%), vomiting (1% to 4%), constipation (children and adolescents ≤4%), abdominal pain (≤3%), toothache (≤3%), nausea (1% to 2%)
Genitourinary: Dysmenorrhea (1% to 2%)
Hypersensitivity: Hypersensitivity (3% to 5%)
Infection: Viral infection (children and adolescents ≤7%), herpes simplex infection (≤4%), bacterial infection (1% to 2%), staphylococcal infection (1% to 2%), varicella (≤1%)
Local: Local irritation (adults ≤6%; children and adolescents ≤1%), local pruritus (1% to 6%), localized erythema (≤2%)
Neuromuscular & skeletal: Arthralgia (≤2%), back pain (≤2%)
Ocular: Conjunctivitis (≤2% to 3%), eye infection (≤1%)
Otic: Otic infection (1% to 6%), otitis media (1% to 3%)
Respiratory: Sore throat (4% to 8%), pharyngitis (children and adolescents 1% to 8%; adults 1%), tonsillitis (children and adolescents ≤6%; adults <1%), asthma (3% to 4%), asthma aggravated (children and adolescents ≤4%), streptococcal pharyngitis (children and adolescents 3%), nasal congestion (1% to 3%), sinusitis (1% to 3%), epistaxis (≤3%), dyspnea (≤2%), flu-like symptoms (≤2%), pneumonia (≤2%), rhinitis (≤2%), rhinorrhea (children and adolescents ≤2%), viral upper respiratory tract infection (≤2%), wheezing (children and adolescents ≤1%)
Miscellaneous: Laceration (children and adolescents ≤2%)
<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, eczema (herpeticum), eye irritation (following application near eyes), facial edema, flushing (ethanol-associated), lymphadenopathy, malignant neoplasm (basal cell carcinoma, squamous cell carcinoma, malignant melanoma, malignant lymphoma), skin discoloration
Hypersensitivity to pimecrolimus or any component of the formulation
Concerns related to adverse effects:
• Infection: Patients with atopic dermatitis are predisposed to skin infections; therapy has been associated with an increased risk of developing eczema herpeticum, varicella zoster, and herpes simplex. Do not apply to areas of active bacterial or viral infection; local infections at the treatment site should be resolved prior to therapy.
• Local symptoms: May cause local symptoms (eg, burning, pruritus, soreness, stinging) during first few days of treatment; usually self-resolving as atopic dermatitis lesions heal.
• Lymphadenopathy: May be associated with development of lymphadenopathy; possible infectious causes should be investigated. Discontinue use in patients with unknown cause of lymphadenopathy or acute infectious mononucleosis.
• Malignancy: [US Boxed Warning]: Topical calcineurin inhibitors (including pimecrolimus) have been associated with rare cases of lymphoma and skin malignancy; avoid use on malignant or premalignant skin conditions (eg, cutaneous T-cell lymphoma).
• Skin papilloma: Skin papilloma (warts) have been observed with use; discontinue use if there is worsening of skin papillomas or they do not respond to conventional treatment.
Disease-related concerns:
• Atopic dermatitis: Diagnosis should be reconfirmed if sign/symptoms do not improve within 6 weeks of treatment.
• Erythroderma: Safety not established in patients with generalized erythroderma.
• Skin diseases which may increase systemic absorption: Not recommended for use in patients with Netherton's syndrome or skin conditions which may increase the potential for systemic absorption.
Special populations:
• Immunocompromised patients: Should not be used in immunocompromised patients, including patients on concomitant systemic immunosuppressive therapy.
• Pediatric: [US Boxed Warning]: Use of pimecrolimus in children <2 years of age is not recommended, particularly since the effect on immune system development is unknown.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.
Other warnings/precautions:
• Appropriate use: [US Boxed Warning]: Continuous long-term use of calcineurin inhibitors (including pimecrolimus) should be avoided and application of cream should be limited to areas of involvement with atopic dermatitis. Safety of intermittent use for >1 year has not been established.
• Sun exposure: Avoid artificial or natural sunlight exposure, even when pimecrolimus is not on the skin.
Clinical trial experience of 436 infants and children <2 years reported a higher incidence of detectable serum concentrations (possibly related to larger BSA:mass ratio) and infection (upper respiratory) or infection-related symptoms than comparative placebo (vehicle) group and older pediatric patients. Pimecrolimus long-term effects on the developing immune system are unknown.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the dermatologic adverse effect of Pimecrolimus. Risk C: Monitor therapy
Corticosteroids (Systemic): Pimecrolimus may enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Immunosuppressants (Cytotoxic Chemotherapy): Pimecrolimus may enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): Pimecrolimus may enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Methotrexate: Pimecrolimus may enhance the immunosuppressive effect of Methotrexate. Risk X: Avoid combination
Adverse events were not observed in animal reproduction studies following topical application.
It is not known if pimecrolimus is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Penetrates inflamed epidermis to inhibit T cell activation by blocking transcription of proinflammatory cytokine genes such as interleukin-2, interferon gamma (Th1-type), interleukin-4, and interleukin-10 (Th2-type). Pimecrolimus binds to the intracellular protein FKBP-12, inhibiting calcineurin, which blocks cytokine transcription and inhibits T-cell activation. Prevents release of inflammatory cytokines and mediators from mast cells in vitro after stimulation by antigen/IgE.
Onset of action: Time to significant improvement: 8 days (Wellington 2001).
Absorption: Topical: Low systemic absorption; blood concentration of pimecrolimus was routinely <2 ng/mL with treatment of atopic dermatitis in adult patients (13% to 62% BSA involvement); blood concentration of pimecrolimus was <3 ng/mL in 26 pediatric patients 2 to 14 years of age with atopic dermatitis (20% to 69% BSA involvement). Significant percutaneous absorption with systemic serum concentrations may occur in children due to the larger surface area to body mass ratio seen in pediatric patients (Segal 2013).
Protein binding: 99.5%, primarily to various lipoproteins.
Metabolism: Hepatic via cytochrome (CYP) P450 3A4.
Half-life elimination: Terminal: Oral: 30 to 40 hours (Wellington 2001)
Time to peak, serum: Topical: 2 to 6 hours
Excretion: Feces (78.4% as metabolites; <1% as unchanged drug)
Cream (Elidel External)
1% (per gram): $11.96
Cream (Pimecrolimus External)
1% (per gram): $10.15 - $10.72
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