4.1. Therapeutic indications

Treatment of patients 3 months of age and older with mild or moderate atopic dermatitis where treatment with topical corticosteroids is either inadvisable or not possible. This may include:

• Intolerance to topical corticosteroids

• Lack of effect of topical corticosteroids

• Use on the face and neck where prolonged intermittent treatment with topical corticosteroids may be inappropriate

4.2. Posology and method of administration

Elidel should be initiated by physicians with experience in the diagnosis and treatment of atopic dermatitis.

Elidel can be used in the short term for the treatment of the signs and symptoms of atopic eczema and intermittently in the long term for the prevention of progression to flares.

Elidel treatment should begin at the first appearance of signs and symptoms of atopic dermatitis. Elidel should only be applied to areas affected with atopic dermatitis. Pimecrolimus should be used for as short period as possible during flares of disease. The patient or caregiver should stop using pimecrolimus when signs and symptoms resolve. Treatment should be intermittent, short-term and not continuous.

If no improvement occurs after 6 weeks, or in case of disease exacerbation, treatment should be stopped. The diagnosis of atopic dermatitis should be re-evaluated and further therapeutic options considered.

Adults

Apply a thin layer of Elidel to the affected skin twice daily and rub in gently and completely. Each affected region of the skin should be treated with pimecrolimus until clearance occurs and then treatment should be discontinued.

Elidel may be used on all skin areas, including the head and face, neck and intertriginous areas, except on mucous membranes. Elidel should not be applied under occlusion (see section 4.4).

In the long-term management of atopic dermatitis (eczema), Elidel treatment should begin at first appearance of signs and symptoms of atopic dermatitis to prevent flares of the disease. Elidel should be used twice daily. Emollients can be applied immediately after using Elidel.

Paediatric population

For infants (3-23 months), children (2-11 years) and adolescents (12-17 years) the posology and method of administration are the same as for adults.

Elderly patients

Atopic dermatitis (eczema) is rarely observed in patients aged 65 and over. Clinical studies with Elidel did not include a sufficient number of patients in this age range to determine whether they respond differently from younger patients.

Method of administration

Elidel should be applied thinly to the affected areas twice daily.

4.3. Contraindications

Hypersensitivity to pimecrolimus, other macrolactams or to any of the excipients (see section 6.1).

4.4. Special warnings and precautions for use

Pimecrolimus cream should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that causes immunosuppression.

Long-term effect on the local skin immune response and on the incidence of skin malignancies is unknown. Pimecrolimus should not be applied to potentially malignant or pre-malignant skin lesions.

Pimecrolimus should not be applied to areas affected by acute cutaneous viral infections (herpes simplex, chicken pox).

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 superficial skin infections including eczema herpeticum (Kaposi's varicelliform eruption), treatment with pimecrolimus may be associated with an increased risk of skin herpes simplex virus infection, or eczema herpeticum (manifesting as rapid spread of vesicular and erosive lesions). In the presence of herpes simplex skin infection, pimecrolimus treatment at the site of infection should be discontinued until the viral infection has cleared.

Patients with severe atopic dermatitis may have an increased risk of skin bacterial infections (impetigo) during treatment with pimecrolimus.

Use of Elidel may cause mild and transient reactions at the site of application, such as a feeling of warmth and/or burning sensation (see section 4.8). If the application site reaction is severe, the risk-benefit of treatment should be re-evaluated.

Care should be taken to avoid contact with eyes and mucous membranes. If accidentally applied to these areas, the cream should be thoroughly wiped off and/or rinsed off with water.

Physicians should advise patients on appropriate sun protection measures, such as minimisation of the time in the sun, use of sunscreen product and covering the skin with appropriate clothing (see section 4.5).

Elidel contains the active substance pimecrolimus, a calcineurin inhibitor. In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies.

Cases of malignancies, including cutaneous and other types of lymphoma, and skin cancers have been reported in patients using pimecrolimus cream (see section 4.8). However, patients with atopic dermatitis treated with Elidel have not been found to have significant systemic pimecrolimus levels.

In clinical studies, 14/1,544 (0.9%) cases of lymphadenopathy were reported while using Elidel 10mg/g cream (see section 4.8). These cases of lymphadenopathy were usually related to infections and noted to resolve upon appropriate antibiotic therapy. Of these 14 cases, the majority had either a clear aetiology or were known to resolve. Patients who receive Elidel 10mg/g cream and who develop lymphadenopathy should have the aetiology of their lymphadenopathy investigated. In the absence of a clear aetiology for the lymphadenopathy, or in the presence of acute infectious mononucleosis, treatment with pimecrolimus should be discontinued. Patients who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves.

Instruct patients not to smoke or go near naked flames - risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.

Populations with potentially higher risk of systemic exposure.

Elidel has not been studied in patients with Netherton's syndrome. Due to the potential for increased systemic absorption of pimecrolimus, Elidel is not recommended in patients with Netherton's syndrome.

As the safety of pimecrolimus has not been established in erythrodermic patients, the use of Elidel in this patient population cannot be recommended.

The use of Elidel under occlusion has not been studied in patients. Occlusive dressings are not recommended.

In patients with severely inflamed and/or damaged skin, the systemic concentrations may be higher.

Elidel contains cetyl alcohol and stearyl alcohol which may cause local skin reactions (e.g. contact dermatitis). Further Elidel also contains 10 mg benzyl alcohol per 1 g cream, which may cause allergic reactions and mild local irritation. Elidel also contains 50 mg propylene glycol (E 1520), per 1 g cream which may cause skin irritation.

4.5. Interaction with other medicinal products and other forms of interaction

Potential interactions between pimecrolimus and other medicinal products have not been systematically evaluated. Pimecrolimus is exclusively metabolised by CYP 450 3A4. Based on its minimal extent of absorption, interactions of pimecrolimus with systemically administered medicinal products are unlikely to occur (see section 5.2).

The present data indicate that pimecrolimus can be used simultaneously with antibiotics, antihistamines and corticosteroids (oral/nasal/inhaled).

Due to the minimal absorption of Elidel, a potential systemic interaction with vaccination is unlikely to occur. In patients with extensive disease, it is recommended to administer vaccinations during treatment-free intervals.

Application of pimecrolimus to vaccination sites, as long as local reactions persist, was not studied and is therefore not recommended. In a 5-year study in infants 3 months to less than 12 months of age at enrolment with mild to moderate atopic dermatitis patients with AD who were treated with Elidel cream or TCS displayed normal immune response maturation and developed effective immunisation against vaccine antigens. (see section 5.1)

There is no experience with concomitant use of immunosuppressive therapies given for atopic eczema such as UVB, UVA, PUVA, azathioprine and cyclosporin A.

Pimecrolimus has no photocarcinogenic potential in animals (see section 5.3.). However, since the relevance to man is unknown excessive exposure of the skin to ultraviolet light including light from a solarium, or therapy with PUVA, UVA or UVB should be avoided during treatment with pimecrolimus.

Rare cases of flushing, rash, burning, itching or swelling have been observed shortly after the intake of alcohol in patients using pimecrolimus cream (see section 4.8).

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of pimecrolimus in pregnant women. Animal studies using dermal application do not indicate direct or indirect harmful effects with respect to embryonal/foetal development. Studies in animals after oral application have shown reproductive toxicity (see section 5.3). Based on the minimal extent of pimecrolimus absorption after topical application of pimecrolimus (see section 5.2), the potential risk for humans is considered limited. However, pimecrolimus should not be used during pregnancy.

Lactation

Animal studies on milk excretion after topical application were not conducted and the use of Elidel in breastfeeding women has not been studied. It is not known whether pimecrolimus is excreted in the milk after topical application.

However, based on the minimal extent of pimecrolimus absorption after topical application of pimecrolimus, (see section 5.2), the potential risk for humans is considered limited. Caution should be exercised when pimecrolimus is administered to breastfeeding women.

Breastfeeding mothers may use Elidel but should not apply Elidel to the breast in order to avoid unintentional oral uptake by the new-born.

Fertility

There are no clinical data on the effects of pimecrolimus on male or female fertility (see section 5.3 Preclinical safety data).

4.7. Effects on ability to drive and use machines

Elidel has no known effect on the ability to drive and use machines.

4.8. Undesirable effects

The most common adverse events were application site reactions which were reported by approximately 19% of the patients treated with Elidel and 16% of patients in the control groups. These reactions generally occurred early in treatment, were mild/moderate and were of short duration.

The following undesirable effects have been observed with the frequencies indicated below during clinical trials using pimecrolimus cream 1% and from spontaneous reporting.

Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000, including isolated reports).

Skin and subcutaneous tissue disorders

Common

Skin infections (folliculitis)

Uncommon

Furuncle, impetigo, herpes simplex, herpes zoster, herpes simplex dermatitis (eczema herpeticum), skin papilloma and condition aggravated

Rare

Allergic reactions (e.g. rash, urticaria, angiooedema), skin discoloration (e.g hypopigmentation, hyperpigmentation)

Metabolism and nutrition disorders

Rare

Alcohol intolerance (in most cases, flushing, rash, burning, itching or swelling occurred shortly after the intake of alcohol)

Infections and infestations

Uncommon

Molluscum contagiosum

General disorders and administration site conditions

Very common

Application site burning

Common

Application site reactions (irritation, pruritus and erythema)

Uncommon

Application site disorders (rash, pain, paraesthesia, desquamation, dryness, oedema)

Immune system disorders

Very rare

Anaphylactic reactions, including severe forms

Post marketing: Cases of malignancy, including cutaneous and other types of lymphoma, and skin cancers, have been reported in patients using pimecrolimus cream (see section 4.4).

Cases of lymphadenopathy have been reported in post-marketing use and in clinical trials, however a causal relationship with the pimecrolimus treatment has not been established (see section 4.4).

Paediatric population

The clinical safety database of children aged 3 months and older treated with pimcrolimus 1% cream is extensive with long-term safety data available for up to 5 years. The safety profiles in infants, children and adolescent were comparable in nature and frequency of the adverse events observed. The most common observed adverse reactions were application site reactions.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at : www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

There has been no experience of overdose with Elidel.