Pimecrolimus

When ATH:
D11AX15

Characteristic.

Ascomycin derivative makrolaktama. White or almost white crystalline powder. Soluble in methanol and ethanol, insoluble in water.

Pharmacological action.
Dermotropic, immunosuppressive, Local anti-inflammatory.

Application.

According to Physicians Desk Reference (2005), pimecrolimus in the form of 1% cream is indicated for the short-term and intermittent long-term treatment of mild to moderate atopic dermatitis in patients with normal immune status at the age of 2 and older, in which the use of alternative conventional therapy is considered undesirable because of the potential risk, or in the treatment of patients, resistant to conventional therapy.

Contraindications.

Hypersensitivity.

Pregnancy and breast-feeding.

In studies of animals embriofetalnogo with dermal application in the form of pimecrolimus 1% cream is not noted on the organism toxicity females and fetuses when used in doses 10 mg/kg/day in rats (0,14 MRDC, based on body surface area), 10 mg/kg/day in rabbits (0,65 MRDC based on AUC comparisons). Cream painted 6 hours per day during the period of organogenesis. (6-21 Th day of pregnancy in rats and 6-20 days gestation in rabbits).

When introduced into the pimecrolimus (for 2 weeks prior to mating and throughout 16 days of pregnancy in rats or rabbits 6-18 days) at doses up to 45 mg / kg / day (38 MRDC based on AUC comparisons) rats and 20 mg / kg / day (3,9 MRDC based on AUC comparisons) rabbits toxicity has not been established in female rats, but marked toxicity embriofetalnaya (postimplantation deaths of fetuses and quantitative reduction of rat offspring, wherein defects in fetuses were observed. In rabbits, there were no toxic influence on the organism substance females, embryotoxicity and teratogenicity.

The study of peri- and postnatal development in rats when administered pimecrolimus inside since the 6th day of pregnancy and up 21 day of lactation showed, When receiving the highest doses 40 mg/kg/day only 2 from 22 females have given birth to live offspring. At doses 10 mg / kg / day (12 MRDC based on AUC comparisons) not marked effect on postnatal survival and development of the F1 generation, subsequent maturation and fertility.

In studies embriofetalnogo development in rats and rabbits show, when administered pimecrolimus inside it passes through the placenta.

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

When pregnancy is possible only when necessary (adequate and well-controlled studies of the safety of use in pregnant women were not conducted, experience of use during pregnancy is limited and does not allow to evaluate the safety of).

Nursing women should stop any breastfeeding, or the use of cream (study drug allocation in breast milk after topical application were not conducted; unknown, whether pimecrolimus penetrates into breast milk).

Side effects.

In studies of the safety of pimecrolimus in the form 1% cream no cases of contact sensitization, phototoxicity, fotoallergii, cumulative inflammation.

In the long-term (1 year) cream alternative study using outer corticosteroids in patients aged 2-17 years 43% patients, apply the cream, It requires the use of corticosteroids (compared with 68% in the control group). Corticosteroids are used more 7 days, 34% the main group and 54% control group. Patients, is used in the study, and a cream and external corticosteroids were more frequent (compared to patients, only applies cream) side effects such as impetigo, skin infections, superimposed infection (infection of atopic dermatitis), rhinitis, hives.

During the 3-randomized, double-blind, controlled pediatric studies (843 Patients of the main group) and one controlled trial in adults (328 the main group) discontinue therapy cream because of side effects 48 patients (4%) of total 1171 patient versus 13 patients (3%) from 408 control patients. The reasons for discontinuation of therapy were mostly application site reactions and skin infections. The most common local reaction, observed during the study, It was burning at the application of the cream (in 8-26% of patients).

Cooperation.

Possible interactions with other drugs (including immunization) We have not been studied systematically. Because of the very low level of pimecrolimus blood when applied topically, systemic effects of the interaction are unlikely, but not excluded. Concomitant administration of inhibitors of CYP3A subfamily enzymes, such as erythromycin, itraconazole, ketoconazole, fluconazole, Calcium channel blockers, cimetidine, etc.. should be conducted with caution.

Overdose.

No cases of overdose with the cream, and accidental ingestion is not observed.

Dosing and Administration.

Outwardly, 2 once a day. The cream is applied in a thin layer to the affected skin and rub gently until completely absorbed. The cream can be applied to the skin of any part of the body, including the head, face, neck, field diaper rash. Treatment is continued until the complete disappearance of symptoms. At the first sign of relapse of atopic dermatitis therapy should be resumed. If symptoms persist for 6 Sun, should re-evaluate the patient's condition.

In the treatment cream can be used for daily moisturizing skin care.

Do not use cream under an occlusive dressing, tk. safety when used under occlusive dressing (may increase systemic exposure) not yet rated.

Precautions.

Do not use cream in children aged up to 2 years.

Do not apply the cream to areas, affected acute viral infection. As the efficacy and safety of cream in the treatment of infection of atopic dermatitis was not carried out, prior to its use is necessary to cure a skin infection, or to assess the risk and the expected benefits from its use.

Patients with atopic dermatitis are predisposed to skin infections, and current treatment may increase the risk of infection by viruses varicella zoster (vetryanaya or opoyasıvayuşçïy not add lïşay) and herpes simplex, or the occurrence of eczema herpetiformis sarcoma.

Local reactions (burning at the site of application), which appear in the first few days of application of the cream (usually disappear within no more 5 days), They have a mild to moderate severity and decrease as improving.

In clinical studies, using a cream reported 14 cases lymphadenopathy (0,9%), mainly related to infections and treatable with antibiotics, However, most of these cases either had a clear etiology, a tendency to normalization. With the development of lymphadenopathy during the application of the cream is necessary to establish the cause; in the absence of a clear etiology of the lymphadenopathy or in the presence of acute infectious mononucleosis application of the cream should be stopped, and observe patients to normalization of.

In clinical studies in patients, using the cream, It was observed 15 cases (1%) development of skin papillomas (The youngest patient was 2 year, the oldest is 12 years). In the case of aggravation of the formation of skin papillomas, or with resistance to standard therapy, you must discontinue use to eliminate warts.

Despite the absence of phototoxicity in applying cream, During treatment, patients should avoid direct sunlight and UV-radiation, tk. carcinogenicity studies in animals have been found to decrease since the beginning of tumors of the skin when exposed to UV radiation during treatment cream.

Data on the use of cream in patients with immune deficiency absent.

Avoid getting the cream in your eyes.