Pimecrolimus

Yes

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Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you receive:

• antifungal medications
• calcium channel blockers
• cimetidine (Tagamet)
• clarithromycin (Biaxin)
• cyclosporine (Neoral, Sandimmune)
• danazol (Danocrine)
• delavirdine (Rescriptor)
• erythromycin (E.E.S., E-Mycin, Erythrocin)
• fluoxetine (Prozac, Sarafem)
• fluvoxamine (Luvox)
• HIV protease inhibitors
• isoniazid (INH, Nydrazid)
• metronidazole (Flagyl)
• nefazodone
• oral contraceptives (birth control pills)
• other ointments, creams, or lotions
• troleandomycin (TAO)
• zafirlukast (Accolate)

This is not a complete list of pimecrolimus drug interactions. For more information, ask your doctor or pharmacist.

WARNING

Long-term Safety of Topical Calcineurin Inhibitors Has Not Been Established

Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including pimecrolimus.

Therefore:

• 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.
• Pimecrolimus is not indicated for use in children less than 2 years of age.

Contraindications

• Known hypersensitivity to pimecrolimus or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Possible increased risk of malignancies.12 13 14 a (See Boxed Warning.)

Malignancies (including lymphoma and skin cancers) reported rarely in children and adults receiving topical pimecrolimus.12 13 14 a Concerns also based on case reports of malignancies (including lymphoma and skin cancers) in patients (including transplant patients) receiving prolonged systemic treatment with calcineurin inhibitors (e.g., cyclosporine, tacrolimus);a animal studies indicating dose-related increases in the risk of lymphoma and other malignancies with pimecrolimus and other calcineurin inhibitors;12 13 14 a and known pharmacologic effects of these immunosuppressants.a 12 13 14

Animal studies using topically or orally administered pimecrolimus in 3 species (mouse, rat, monkey) indicate increased risk of lymphoma and other malignancies (possibly due to immunosuppression10 12 14 );a risk appears to be related to dose and duration of exposure.12 13 14 a

Risk associated with systemic therapy is related to intensity and duration of immunosuppression.a The potential for systemic immunosuppression with topical pimecrolimus and the drug’s role in the development of malignancies in humans have not been established.12 13 14 a Long-term studies in humans are needed to determine whether topical pimecrolimus is associated with an increased risk of malignancies.12 13 Until such data are available, FDA recommends limiting use to the labeled indication, reserving the drug for use as a second-line agent for short-term and intermittent treatment.12 13 (See Atopic Dermatitis under Uses, see Immunocompromised Patients under Cautions, and see Dosage and Administration.) Carefully evaluate potential risks and benefits of therapy.12 13

Avoid use for malignant or premalignant skin conditions (e.g., cutaneous T-cell lymphoma [CTCL]), which may appear clinically similar to dermatitis.a

General Precautions

Lymphadenopathy reported; usually related to infections and resolves following appropriate anti-infective therapy.1 Also reported in association with malignancy.14 Investigate etiology if lymphadenopathy develops.1 Discontinue pimecrolimus in the absence of a clear etiology or in the presence of acute infectious mononucleosis.a Monitor patients with lymphadenopathy to ensure that it resolves.1

Not recommended for use in patients with Netherton’s syndrome because of the potential for increased systemic absorption of pimecrolimus.1

Safety in patients with generalized erythroderma has not been established.a

Mild to moderate sensation of warmth and/or burning, stinging, soreness, and pruritus at the treatment site may occur within 1–5 days of initiating therapy.a b Reactions usually last no more than 5 days and improve as the lesions of atopic dermatitis resolve.1

Clinical infections (e.g., bacterial, viral) at treatment sites should be resolved before initiating pimecrolimus therapy.1 Safety and efficacy not established for treatment of clinically infected atopic dermatitis.1

Possible increased risk of varicella-zoster infections (chickenpox or shingles), herpes simplex virus infection, or eczema herpeticum.1

Skin papilloma and/or warts may occur.1 If skin papilloma worsens or is unresponsive to conventional therapy, consider discontinuing pimecrolimus until complete resolution of the warts is achieved.1

Septic arthritis reported in infants ≤1 year of age during clinical trials; however, causality not established.a

Although phototoxicity not reported in humans, it may be prudent to minimize or avoid natural or artificial sunlight exposure during pimecrolimus therapy (including periods when no drug is on skin).1 Potential effects on skin response to ultraviolet (UV) damage are not known.a

Animal photocarcinogenicity studies indicate shortened time to skin tumor formation following chronic topical pimecrolimus dosing with concurrent UV radiation exposure.1

Safety and efficacy not established and not recommended for use in immunocompromised adults or children.1 12 13 14 a

Specific Populations

Category C.1

Not known whether distributed into milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established and not recommended for use in children <2 years of age.1 12 a c

Increased incidence of upper respiratory tract infections in infants <24 months of age receiving pimecrolimus compared with those receiving placebo.12 Possible increased incidence of upper respiratory symptoms and/or infections in infants 3–23 months of age compared with older children; relationship to treatment not known.1

Long-term effects on the developing immune system in infants and children are not known.12 13 14 a

Not recommended for use in immunocompromised children.1 12 13 14

Experience insufficient to determine whether patients ≥65 years of age respond differently than younger adults.1

Common Adverse Effects

Upper respiratory tract infection,1 3 b cough,1 3 b nasopharyngitis,1 b application site reactions (e.g., sensation of burning or warmth),1 3 b headache.1 3 b

Absorption

Bioavailability

Not appreciably absorbed into systemic circulation following multiple topical applications in adults or children 2–14 years of age with atopic dermatitis.1 2 3 Increased systemic absorption occurs following topical application in infants 3–23 months of age with atopic dermatitis compared with older children, possibly because of the larger surface area to body mass ratio.1 14

Occlusive dressings or wrappings may promote systemic exposure.1

Distribution

Extent

Crosses placenta in rats and rabbits following oral administration.1

Plasma Protein Binding

74–87% bound to plasma proteins in vitro.1

Elimination

Metabolism

Studies using oral pimecrolimus indicate absorbed drug is metabolized in the liver principally via demethylation by CYP3A isoenzymes.1 3

No evidence of skin-mediated metabolism.1

Elimination Route

Studies using oral pimecrolimus indicated absorbed drug is eliminated principally in feces as metabolites.1

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about this medicine (pimecrolimus), please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine (pimecrolimus). It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine (pimecrolimus).

Review Date: October 4, 2017

• Elidel

Apply a thin layer to the affected area twice daily and rub in gently and completely

Comments:
-Therapy should be discontinued when signs (e.g., itch, rash, redness) resolve.
-If symptoms persist beyond 6 weeks, patients should be reexamined by their health care provider to confirm the diagnosis of atopic dermatitis.

Use: As second-line therapy for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable

2 years and older:
Apply a thin layer to the affected area twice daily and rub in gently and completely

Comments:
-The long-term safety and effects of this drug on the developing immune system are unknown.
-Therapy should be discontinued when signs (e.g., itch, rash, redness) resolve.
-If symptoms persist beyond 6 weeks, patients should be reexamined by their health care provider to confirm the diagnosis of atopic dermatitis.

Use: As second-line therapy for the short-term and noncontinuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable

Data not available