Elidel® [Pimecrolimus]

Pharmacological properties

pimecrolimus is a derivative of macrolactam ascomycin with an anti-inflammatory effect and a selective inhibitor of the formation and release of mediators of cytokine inflammation. pimecrolimus to a large extent specifically binds to macrophyllin-12 and inhibits calcium-dependent phosphatase calcineurin. as a consequence, it inhibits the activation of t-lymphocytes, blocking the transcription of previously released cytokines.

Pimecrolimus combines high anti-inflammatory activity and a slight effect on systemic immune responses.

Pharmacokinetics After external use of pimecrolimus on the skin, its blood level is very low, therefore, the metabolism of the drug cannot be determined. In vitro plasma protein binding studies have shown that 99.6% of pimecrolimus is in a protein bound state. Most of pimecrolimus in plasma is associated with various lipoproteins.

In humans, in vitro metabolism of the drug was not observed.

Indications

Treatment of patients aged 2 years with mild and moderate atopic dermatitis, if treatment with local corticosteroids is undesirable or impossible. it can be at:

• intolerance to local corticosteroids;
• insufficient effect of local corticosteroids;
• the need for use on the face and neck, where prolonged periodic use of corticosteroids may be inappropriate.

Application

The duration of treatment is determined by the doctor depending on the stage and severity of the disease.

Elidel can be used shortly to treat signs and symptoms of atopic eczema and periodically for a long time to prevent exacerbation of the disease. Treatment should begin when the first signs and symptoms of atopic dermatitis appear.

Elidel should be applied only to areas affected by atopic dermatitis. Elidel must be used for the shortest time during an exacerbation of the disease. The patient or caregiver should stop using Elidel when symptoms disappear. Treatment should be periodic, short-term and short-lived.

Elidel should be applied in a thin layer to the affected areas 2 times a day.

Research data confirm the periodic use of Elidel for up to 12 months.

If after 6 weeks no improvement is noted or if the condition worsens, the use of Elidel should be discontinued. In this case, it is necessary to reassess the diagnosis of atopic dermatitis and consider further therapeutic measures.

Adults A thin layer of Elidel is applied to the affected skin 2 times a day and completely rubbed into the skin with light movements. Each of the affected areas should be treated with Elidel until the signs and symptoms of the disease disappear, after which treatment should be discontinued.

Elidel can be used on all skin areas, including the head, face, neck and intertriginous region (the area of ​​inguinal folds and genitals), except for mucous membranes. Elidel should not be used in places under tight dressings.

With prolonged therapy of atopic dermatitis (eczema), treatment with Elidel should be started when the first signs and symptoms of atopic dermatitis appear, in order to prevent the spread and further exacerbation of the disease. Elidel should be used 2 times a day. Immediately after applying Elidel, it is necessary to apply emollients. For children, the dose and method of application do not differ from the recommendations for adult patients.

Elderly patients. In patients over the age of 65, cases of atopic dermatitis (eczema) are rarely detected. Clinical studies on the study of Elidel did not include a sufficient number of patients in this age category to determine whether their response to treatment is different from the response of younger patients.

Contraindications

Hypersensitivity to pimecrolimus, other macrolactams or other components of the drug.

Side effects

Infections: molluscum contagiosum.

From the immune system: anaphylactic reactions, including severe forms.

From the side of metabolism and nutrition: intolerance to alcohol (in most cases, hot flashes, rash, burning, itching or swelling that occur immediately after drinking alcohol).

On the part of the skin and subcutaneous tissue: skin infections (folliculitis), boils, impetigo, herpes simplex, herpes zoster, herpes dermatitis (herpes eczema), skin papilloma and worsening, allergic reactions, including rash, urticaria, angioedema, skin discoloration (hypopigmentation, hyperpigmentation).

General disorders and local reactions: burning at the place of application of the cream, reactions at the place of application (irritation, itching, erythema, rash, pain, paresthesia, peeling, dryness, swelling).

The period of post-marketing use of the drug. In some cases, patients who used pimecrolimus-based cream noted malignant neoplasms, including skin and other types of lymphomas, as well as skin cancer, although a causal relationship has not been established.

Cases of the development of lymphadenopathy have been reported in post-marketing and clinical studies, but a causal relationship with Elidel treatment has not been established.

special instructions

Elidel is not recommended for use in patients with hereditary or acquired immunodeficiency or in patients receiving treatment with immunosuppressive drugs.

The long-term effect on the local immune response of the skin and on the incidence of malignant skin diseases is unknown. Elidel should not be applied to potentially malignant lesions or skin areas affected by precancerous diseases. Elidel should not be used on skin areas affected by acute viral infections (herpes simplex, chickenpox).

The efficacy and safety of Elidel was not evaluated in the treatment of clinically infected atopic dermatitis. Before starting treatment with Elidel, areas affected by the infection must be cured.

Since patients with atopic dermatitis are prone to superficial skin infections, including herpetic eczema (Kaposis herpes eczema), treatment with Elidel may increase the risk of herpes simplex virus infection or herpes eczema, in which case Elidel treatment should be discontinued until the viral infection disappears.

Patients with acute atopic dermatitis have an increased risk of bacterial skin infections (impetigo) when treated with Elidel.

The use of Elidel may cause minor transient reactions at the site of application, such as a feeling of warmth and / or burning. Patients should inform the doctor if the reactions at the site of application of the drug are significantly pronounced.

It is not recommended to use the drug under an occlusive dressing.

Avoid contact with eyes and mucous membranes. If the product accidentally gets into these areas, it should be thoroughly wiped or rinsed with water.

The physician should recommend appropriate sun protection measures to the patient, such as restricting exposure to the sun, using protective equipment, and covering the skin with clothing.

Elidel contains cetyl and stearyl alcohol, which can cause local skin reactions. Elidel also contains propylene glycol, which can cause skin irritation.

Elidel contains the active substance pimecrolimus, a calcineurin inhibitor. In patients after transplantation and prolonged systemic use of immunosuppressants, systemic use of calcineurin inhibitors is associated with an increased risk of lymphomas and malignant skin diseases.

Cases of the occurrence of malignant diseases, including skin and other forms of lymphomas and malignant skin tumors in patients who used pimecrolimus cream, were also reported.However, patients with atopic dermatitis who were treated with Elidel did not reveal a significant systemic level of pimecrolimus.

During clinical studies of Elidel 10 mg / g, lymphadenopathy was observed in 0.9% of cases. They were usually associated with infections and disappeared with appropriate antibiotic therapy, but most of them had a clear etiology or disappeared on their own. Therefore, with the appearance of lymphadenopathy in patients using Elidel at a dose of 10 mg / g, the etiology of this process should be clarified. In the absence of an obvious etiology of lymphadenopathy or with the appearance of acute infectious mononucleosis, treatment with this drug should be discontinued. Monitoring of patients with advanced lymphadenopathy is necessary in order to confirm its disappearance.

Patient groups with a potentially high risk of systemic exposure. Studies of the use of Elidel have not been performed in patients with Nethertons syndrome. Due to the possibility of higher systemic absorption of pimecrolimus, the use of Elidel in patients with Nethertons syndrome is not recommended.

Since the safety of Elidel for patients with erythroderma was not evaluated, the drug is not recommended for this group of patients.

In patients with acute inflammatory processes of the skin or its damage, the systemic concentration may be higher.

During pregnancy and breastfeeding. There are no sufficient data on the use of Elidel in pregnant women. Animal studies with external use did not reveal a direct or indirect negative effect on the fetal / intrauterine development of the fetus. Animal studies with oral administration indicate reproductive toxicity.

Due to the minimal level of absorption of pimecrolimus after topical application of Elidel, the possible risk to humans is considered limited. However, Elidel should not be used during pregnancy.

Elidel should be used with caution in women who are breast-feeding.

Women who are breastfeeding can use Elidel, but should not apply it to the chest area in order to avoid inadvertent ingestion of the drug in the oral cavity of infants.

Children. The use of Elidel in children under the age of 2 years is not recommended.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Elidels influence on the ability to drive vehicles and work with mechanisms has not been established.

Interactions

Possible interactions of Elidel with other drugs have not been systematically evaluated. pimecrolimus is metabolized exclusively by cyp 3a4. Given the minimum level of absorption, the interaction of Elidel with drugs that are used systemically is unlikely.

These data indicate that Elidel can be used simultaneously with antibiotics, antihistamines, and glucocorticoids (oral, nasal, or inhaled).

Given the minimal absorption level, Elidels systemic interaction with vaccination is unlikely. However, such studies have not been conducted. Therefore, patients with common or disseminated forms of the disease are recommended to be vaccinated during periods when the drug is not used.

There is no data on the simultaneous use of immunosuppressive drugs prescribed for atopic eczema, such as ultraviolet radiation of spectrum B and A, PUVA therapy (psoralen and ultraviolet radiation of spectrum A), azathioprine and cyclosporine. Excessive irradiation of the skin with ultraviolet rays (including the use of tanning salons, ultraviolet radiation therapy of spectrum B and A and PUVA therapy) should be avoided during treatment with Elidel.

Rare cases of redness, rashes, burning sensation, itching or swelling immediately after drinking alcohol in patients who used pimecrolimus cream were noted.

Overdose

There are no reports of cases of overdose of Elidel.

Storage conditions

At a temperature not exceeding 25 ° C, do not freeze. after opening the tube, use the drug for 12 months.