Elidel

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medicine.

• Valeant Pharmaceuticals North America LLC

Elidel is part of the drug class:

• Agents for dermatitis, excluding corticosteroids

Before you start using Elidel, tell your doctor about all of your medical conditions, including if you:

• have a skin disease called Netherton’s syndrome (a rare inherited condition)
• have any infection on your skin including chicken pox or herpes
• have been told you have a weakened immune system 
• are pregnant, breastfeeding, or planning to become pregnant.

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. 

Use Elidel exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

Elidel is usually applied in a thin layer to the affected skin twice daily.

Immunosuppressive agent; derivative of ascomycin (a macrolactam); structurally related to tacrolimus.1 3 4 6 7

No formal drug interaction studies have been performed.1

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction with inhibitors of CYP3A4 in patients with widespread and/or erythrodermic disease.1

Specific Drugs

• Importance of reading the patient information (medication guide) provided by the manufacturer before initiating therapy and each time the prescription is refilled.b

• Importance of informing clinicians of other medical conditions, including Netherton’s syndrome, skin infections (e.g., chicken pox, herpes), or weakened immune system.b

• Advise patients that pimecrolimus is for external use on affected areas of the skin only.a Importance of patients or caregivers washing their hands before and after application if hands are not an area for treatment.1

• Importance of ensuring that the skin is completely dry before applying the drug.a Advise patients not to bathe, shower, or swim immediately after application.b

• Importance of avoiding contact with the eyes; irrigate eyes with copious amounts of cool water if contact occurs.a

• Importance of following the clinician’s advice regarding use of other topical preparations; importance of maintaining good skin care practices; apply moisturizers (if used) after pimecrolimus.a

• Advise patients to discontinue pimecrolimus when the signs and symptoms (e.g., itching, rash, redness) of atopic dermatitis (eczema) resolve, or as directed by clinician.a Importance of following the clinician’s advice if symptoms recur after a course of treatment.a

• Importance of not using the drug in children <2 years of age.a

• Importance of avoiding use of bandages, dressings, or wrappings on treated skin.b

• Importance of not using the drug for any disorder other than that for which it was prescribed.1

• Importance of using pimecrolimus exactly as prescribed and of not using the drug continuously for a long period of time.a 1 Importance of using the minimum amount required to control signs and symptoms of atopic dermatitis; importance of using the drug for short-term or intermittent therapy (e.g., courses repeated after treatment-free intervals) only.12 13 a

• Importance of reporting persistently swollen glands or any other adverse reactions to clinician.1 b Importance of notifying clinician if reaction at treatment site (e.g., warmth and/or burning) is severe or persists >1 week.1

• Importance of notifying clinician if the signs and symptoms of atopic dermatitis do not improve after 6 weeks of therapy or at any time become noticeably worse.1

• Importance of notifying clinician if a skin infection develops during treatment with pimecrolimus.a

• Importance of avoiding or limiting exposure of unprotected skin to natural or artificial sunlight (tanning beds or UVA/B light) while using pimecrolimus cream (even when the drug is not on the skin); wear protective clothing and use a broad-spectrum sunscreen with a high protection factor.1 a

• Importance of not swallowing pimecrolimus; contact clinician if swallowed.a

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs, dietary supplements, herbal supplements, any other skin product, or any form of phototherapy (UVA or UVB).1 b

• Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients of other important precautionary information. (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Use Elidel as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to take this medicine as you have been told by your doctor. Do not use more than you were told to use.
• Do not take Elidel (pimecrolimus) by mouth. Use on your skin only. Keep out of your mouth, nose, and eyes (may burn).
• Wash your hands before and after use. Do not wash your hands after use if putting this on your hand.
• Put on clean, dry skin.
• Put a thin layer on the affected skin and rub in gently.
• Do not use on open wounds or infected skin.
• Avoid putting on healthy skin.
• Do not use coverings (bandages, dressings, make-up) unless told to do so by the doctor.
• Do not bathe, shower, or swim right after putting on.
• Stop this medicine when health problem is gone.
• Use Elidel for short periods of time. If signs show up again, talk with the doctor.
• If your signs do not get better after 6 weeks of care, talk with your doctor.

What do I do if I miss a dose?

• Put on a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not put on 2 doses at the same time or extra doses.

ElidelCream, 1%, for topical use, contains the compound pimecrolimus, the immunosuppressant 33-epi-chloro-derivative of the macrolactam ascomycin.

Chemically, pimecrolimus is (1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-12-[(1E)-2-{(1R,3R,4S)-4-chloro-3-methoxycyclohexyl}-1-methylvinyl]-17-ethyl-1, 14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone. The compound has the empirical formula C43H68ClNO11 and the molecular weight of 810.47. The structural formula is:

Pimecrolimus is a white to off-white fine crystalline powder. It is soluble in methanol and ethanol and insoluble in water.

Each gram of Elidel Cream, 1% contains 10 mg of pimecrolimus in a whitish cream base of benzyl alcohol, cetyl alcohol, citric acid anhydrous, mono- and diglycerides, oleyl alcohol, propylene glycol, sodium cetostearyl sulphate, sodium hydroxide, stearyl alcohol, triglycerides and water.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year rat dermal carcinogenicity study using Elidel Cream, 1%, a statistically significant increase in the incidence of follicular cell adenoma of the thyroid was noted in low, mid and high dose male animals compared to vehicle and saline control male animals. Follicular cell adenoma of the thyroid was noted in the dermal rat carcinogenicity study at the lowest dose of 2 mg/kg/day [0.2% pimecrolimus cream; 1.5X the Maximum Recommended Human Dose (MRHD) based on AUC comparisons]. No increase in the incidence of follicular cell adenoma of the thyroid was noted in the oral carcinogenicity study in male rats up to 10 mg/kg/day (66X MRHD based on AUC comparisons). However, oral studies may not reflect continuous exposure or the same metabolic profile as by the dermal route. In a mouse dermal carcinogenicity study using pimecrolimus in an ethanolic solution, no increase in incidence of neoplasms was observed in the skin or other organs up to the highest dose of 4 mg/kg/day (0.32% pimecrolimus in ethanol) 27X MRHD based on AUC comparisons. However, lymphoproliferative changes (including lymphoma) were noted in a 13-week repeat dose dermal toxicity study conducted in mice using pimecrolimus in an ethanolic solution at a dose of 25 mg/kg/day (47X MRHD based on AUC comparisons). No lymphoproliferative changes were noted in this study at a dose of 10 mg/kg/day (17X MRHD based on AUC comparison). However, the latency time to lymphoma formation was shortened to 8 weeks after dermal administration of pimecrolimus dissolved in ethanol at a dose of 100 mg/kg/day (179-217X MRHD based on AUC comparisons).

In a mouse oral (gavage) carcinogenicity study, a statistically significant increase in the incidence of lymphoma was noted in high dose male and female animals compared to vehicle control male and female animals. Lymphomas were noted in the oral mouse carcinogenicity study at a dose of 45 mg/kg/day (258-340X MRHD based on AUC comparisons). No drug-related tumors were noted in the mouse oral carcinogenicity study at a dose of 15 mg/kg/day (60-133X MRHD based on AUC comparisons).

In an oral (gavage) rat carcinogenicity study, a statistically significant increase in the incidence of benign thymoma was noted in 10 mg/kg/day pimecrolimus treated male and female animals compared to vehicle control treated male and female animals. In addition, a significant increase in the incidence of benign thymoma was noted in another oral (gavage) rat carcinogenicity study in 5 mg/kg/day pimecrolimus treated male animals compared to vehicle control treated male animals. No drug-related tumors were noted in the rat oral carcinogenicity study at a dose of 1 mg/kg/day male animals (1.1X MRHD based on AUC comparisons) and at a dose of 5 mg/kg/day for female animals (21X MRHD based on AUC comparisons).

In a 52-week dermal photocarcinogenicity study, the median time to onset of skin tumor formation was decreased in hairless mice following chronic topical dosing with concurrent exposure to UV radiation (40 weeks of treatment followed by 12 weeks of observation) with the Elidel Cream, 1% vehicle alone. No additional effect on tumor development beyond the vehicle effect was noted with the addition of the active ingredient, pimecrolimus, to the vehicle cream.

A 39-week oral monkey toxicology study was conducted with pimecrolimus doses of 15, 45 and 120 mg/kg/day. A dose-dependent increase in expression of immunosuppressive-related lymphoproliferative disorder (IRLD) associated with lymphocryptovirus (a monkey strain of virus related to human Epstein Barr virus) was observed. IRLD in monkeys mirrors what has been noted in human transplant patients after chronic systemic immunosuppressive therapy, post-transplantation lymphoproliferative disease (PTLD), after treatment with chronic systemic immunosuppressive therapy. Both IRLD and PTLD can progress to lymphoma, which is dependent on the dose and duration of systemic immunosuppressive therapy. A dose-dependent increase in opportunistic infections (a signal of systemic immunosuppression) was also noted in this monkey study. A no observed adverse effect level (NOAEL) for IRLD and opportunistic infections was not established in this study. IRLD occurred at the lowest dose of 15 mg/kg/day for 39 weeks [31X the Maximum Recommended Human Dose (MRHD) of Elidel Cream, 1% based on AUC comparisons] in this study. A partial recovery from IRLD was noted upon cessation of dosing in this study.

A battery of in vitro genotoxicity tests, including Ames assay, mouse lymphoma L5178Y assay, and chromosome aberration test in V79 Chinese hamster cells and an in vivo mouse micronucleus test revealed no evidence for a mutagenic or clastogenic potential for the drug.

An oral fertility and embryofetal developmental study in rats revealed estrus cycle disturbances, post-implantation loss and reduction in litter size at the 45 mg/kg/day dose (38X MRHD based on AUC comparisons). No effect on fertility in female rats was noted at 10 mg/kg/day (12X MRHD based on AUC comparisons). No effect on fertility in male rats was noted at 45 mg/kg/day (23X MRHD based on AUC comparisons), which was the highest dose tested in this study.

A second oral fertility and embryofetal developmental study in rats revealed reduced testicular and epididymal weights, reduced testicular sperm counts and motile sperm for males and estrus cycle disturbances, decreased corpora lutea, decreased implantations and viable fetuses for females at 45 mg/kg/day dose (123X MRHD for males and 192X MRHD for females based on AUC comparisons). No effect on fertility in female rats was noted at 10 mg/kg/day (5X MRHD based on AUC comparisons). No effect on fertility in male rats was noted at 2 mg/kg/day (0.7X MRHD based on AUC comparisons).

Elidel®
(pimecrolimus) cream 1%

Net Wt. 5 g

FOR TOPICAL USE ONLY.
NOT FOR OPHTHALMIC USE.

If Elidel Cream gets in your eyes,
rinse your eyes with cold water.

ATTENTION PHARMACIST:
Each patient is required to receive
the enclosed Medication Guide.

Rx only

SAMPLE – NOT FOR RESALE

Elidel (pimecrolimus) is an immunosuppressant. It works by decreasing your body's immune system to help slow down the growth of atopic dermatitis (eczema) on your skin.

Elidel Cream is used to treat severe atopic dermatitis (eczema} when other medications have not worked well.

Elidel Cream may also be used for purposes not listed in this medication guide.

Use Elidel only on the skin, exactly as it was prescribed for you. Follow the directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended. Elidel Cream is not for long-term use.

Use Elidel only on skin areas affected with eczema. Stop using the medicine once your symptoms have cleared up, unless your doctor has told you otherwise.

Elidel Cream is for use on the skin only (topical). Do not get the cream in your eyes, nose, mouth, vagina, or rectum.

Wash your hands before and after using this medicine, unless you are using the medication to treat a hand condition.

Apply the medicine only to clean, dry skin. Use the smallest amount needed to apply a thin layer to the skin areas diagnosed with atopic dermatitis. Rub in gently.

Do not cover the treated skin with a bandage. Bandaging can increase the amount of drug you absorb through your skin and may cause harmful effects. Do not bathe, shower, or swim right after applying Elidel. Water may wash off the medicine.

Right after applying Elidel, you may need to rub in a moisturizing cream or lotion to keep your skin from getting too dry. Ask your doctor about which cream or lotion to use.

Elidel can lower the blood cells that help your body fight infections. This can make it easier for you to get sick from a virus such as chicken pox or herpes (cold sores or shingles). Tell your doctor if you have been exposed to any illness, or if you have any signs of infection such as fever, chills, sore throat, or flu symptoms.

Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.

Store at room temperature. Do not freeze. Keep the medicine tube tightly capped when not in use.

Applies to pimecrolimus topical: topical cream

Along with its needed effects, pimecrolimus topical (the active ingredient contained in Elidel) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking pimecrolimus topical:

• Abdominal or stomach pain
• body aches or pain
• burning, itching, redness, skin rash, swelling, or soreness at the application site
• change in hearing
• chills
• cold or flu-like symptoms
• congestion (ear or nasal)
• cough producing mucus
• diarrhea
• difficulty with breathing or shortness of breath
• dryness or soreness of the throat
• earache or pain in the ear
• ear drainage
• fever
• general feeling of discomfort or illness
• headache
• hoarseness
• itching
• joint pain
• loss of appetite
• loss of voice
• muscle aches and pains
• nausea
• pain
• redness
• runny nose
• shivering
• sneezing
• sweating
• swelling
• tenderness
• tender, swollen glands in the neck
• tightness in the chest
• trouble with swallowing
• trouble with sleeping
• unusual tiredness or weakness
• voice changes
• vomiting
• warmth on the skin
• wheezing

• Blistering, crusting, irritation, itching, or reddening of the skin
• blurred vision or other change in vision
• eye pain
• fast heartbeat
• hives
• itchy, raised, round, smooth, skin-colored bumps found on just one area of the body that are oozing, thick, white fluid
• irritation
• joint pain, stiffness or swelling
• rash
• redness of the eye
• redness of the skin
• sensitivity of the eyes to light
• skin rash on the face, scalp, or stomach
• swelling of the eyelids, face, lips, hands, or feet
• tearing
• troubled breathing or swallowing

• Black, tarry stools
• change in size, shape, or color of existing mole
• cough
• dizziness
• itching, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• large, hive-like swelling on the face
• mole that leaks fluid or bleeds
• new mole
• small, red skin lesion, growth, or bump usually on the face, ears, neck, hands, or arms
• sores that will not heal
• weight loss
• yellow eyes and skin

Some side effects of pimecrolimus topical may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Burning, itching, and pain in hairy areas
• pus at the root of the hair

• Blemishes on the skin
• bloody nose
• burning or stinging of the skin
• difficulty having a bowel movement (stool)
• flushing; redness of skin; unusually warm skin at site
• heavy bleeding
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• pimples
• redness or swelling in the ear
• vaginal pain and cramps

• Burning, stinging, itching, or mild discomfort of the eye (after applying the cream to the eyelids or near the eyes)
• feeling of warmth (with alcohol use)
• redness of the face, neck, arms, and occasionally, upper chest (with alcohol use)