Retapamulin - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Other antibiotics

Included in the formulation

Altargo®

ointment externally

GlaxoSmithKline Trading, ZAO Russia

АТХ:

D.06.A.X Other antibiotics for external use

D.06.A.X.13 Retapamulin

Pharmacodynamics:Retapamulin is a semi-synthetic derivative of pleuromutilin, which is isolated by fermentation from Clitopllus passeckerianus.

Retapamulin selectively inhibits protein synthesis in a bacterial cell by interaction with a 50S subunit ribosome bacteria in a way that differs from the mechanisms of action of all other non-pleuromutilin antibiotics that interact with the ribosomes of bacteria.

The binding site includes the ribosomal protein L3 and the ribosomal center of P, as well as the center of the peptidyl transferase. Linking to this center, pleuromutilins inhibit peptidyl transfer, partially block the interaction with the center of P and prevent the normal formation of active ribosomal subunits of 50S, which leads to inhibition of protein synthesis by a bacterial cell through various mechanisms.

Due to the special mechanism of action, the cross-resistance of retapamulin and other classes of antibiotics against specific pathogens, according to research in vitro, was rare.

According to research in vitro and clinical research retapamulin is active against most strains of the main pathogens of skin infections and its appendages (Staphylococcus aureus and Streptococcus pyogenes). At the same time, in clinical conditions retapamulin It is less effective for some methicillin-resistant strains Staphylococcus aureus.

In addition, the drug has activity in vitro in relation to some other gram-positive, gram-negative and anaerobic bacteria.

Retapamulin has predominantly bacteriostatic action against pathogens S. aureus and S. pyogenes.

Retapamulin in vitro is active against most strains Staphylococcus epidermidis, Steptococcus agalactiae, Steptococcus viridans, Proplonibaclerium acnes, Peptostreptococcus spp., Prevotella spp., Fusobacterium spp. and Porphyromonas spp.

Resistance

In connection with the specific mechanism of action, the cross-resistance of retapamulin and other classes of antibiotics in relation to specific pathogens according to research data in vitro was rare.

Retapamulin demonstrated a low ability to develop resistance in conditions in vitro. The highest minimum inhibitory concentration on the basis of the sequential passage data S. aureus and S. pyogenes in the presence of subminimal inhibitory concentrations (sub-MIC) of retapamulin was 2 μg / ml.During the treatment with the drug during the program of clinical study of the development of resistance to retapamulin was not observed.

Pharmacokinetics:

Systemic absorption after local application of retapamulin through intact skin in healthy volunteers was very low. C_max after a single application of 1% retapamulin ointment per 200 cm² the damaged skin was 22.1 ng / ml.

In most plasma samples in adult patients and children who received external treatment with retapamulin twice a day for secondary traumatic injuries, the concentration of the drug was below the limit of quantification (0.5 ng / ml). The maximum detected retapamulin concentration in adults was 10.7 ng / ml, and in children (age 2-17 years) it was 18.5 ng / ml.

Retapamulin is not indicated for the treatment of children under 9 months of age.

Co-administration with ketoconazole

The combined use of ketoconazole for oral administration at a dose of 200 mg twice daily against daily daily external application of retapamulin 1% ointment on the damaged skin of healthy adult men increased the AUC (0-24) and C_max retapamulin by 81%.The combined use of retapamulin and inhibitors of the isoenzyme CYP3A4 (eg, ketoconazole) in children has not been studied. Due to low systemic absorption of the drug after its topical application in adults and children aged 2 years and older, when joint administration of inhibitors of the isoenzyme CYP3A4, correction of the dose of retapamulin in these patients is not required.

Distribution of the drug in the tissues of the human body has not been studied. Retapamulin binds to blood plasma proteins by about 94%.

According to studies of human hepatocytes in vitro, the main metabolic pathways included monoxidation and dioxygenation. The main isoenzyme responsible for the metabolism of retapamulin in human liver microsomes is CYP3A4.

The removal of retapamulin from the human body has not been studied.

Indications:

Treatment of infections of the skin and its appendages caused by microorganisms sensitive to retapamulin, namely Staphylococcus aureus and Streptococcus pyogenes:

- Primary impetigo;

- Secondarily infected traumatic injuries, for example, small cuts, abrasions, edges of the sutured wound;

- Secondarily infected dermatoses, including pustular psoriasis, complicated atopic and contact dermatitis.

ICD-10

I.B95-B97.B95 Streptococci and staphylococci as a cause of diseases classified elsewhere

XII.L00-L08.L01 Impetigo

XII.L20-L30.L30.3 Infectious dermatitis

XIX.T79.T79.3 Post-traumatic wound infection, not elsewhere classified

Contraindications:

- hypersensitivity to retapamulin or any other component of the ointment;

- Children's age up to 9 months.

Carefully:

Since inhibitors of the CYP3A4 isoenzyme may additionally increase the systemic absorption of retapamulin, caution should be exercised when using inhibitors of the CYP3A4 isoenzyme with retapamulin in young children.

Pregnancy and lactation:

The drug is not recommended in connection with the lack of sufficient experience in the use of retapamulin in pregnant women. Influence on postnatal development of the child was not evaluated. The safety of the use of retapamulin in the lactation period has not been studied. During lactation, the drug is not recommended due to the lack of data on the penetration of the drug into breast milk.

Category of recommendations FDA is not defined.

Dosing and Administration:

Apply a thin layer on the affected area of the skin twice a day for five days.

A sterile gauze bandage can be applied to the treated area.

If there is no clinical effect within 3-4 days, treatment should be reviewed.

Side effects:From the skin and subcutaneous fat: infrequently - contact dermatitis.

General and local reactions (reactions in the place of application): often - irritation, infrequently - itching, pain, erythema.

From the immune system: allergic reactions, including Quincke angioedema.

Overdose:

There are no known cases of overdose of retapamulin.

There is no specific antidote to the drug.

Interaction:Clinically significant drug interactions in adults are unknown.
Studies on the study of drug interactions in children have not been conducted. Children under the age of 2 years had an increase in systemic absorption of retapamulin. The combined use of retapamulin and other external agents on the same skin area has not been studied and is not recommended.

Special instructions:

In case of an allergic reaction or severe local irritation after application of retapamulin ointment, treatment should be discontinued, the remnants of the ointment removed from the skin, an alternative treatment for the existing infection.

Do not apply on eyes; retapamulin was not studied in ophthalmic practice.

Do not apply to mucous membranes; the efficacy and safety of applying retapamulin to mucous membranes have not been investigated. There have been cases of nasal bleeding when applying retapamulin on the nasal mucosa.

Do not take internally.

As with other antibiotics, prolonged use of retapamulin ointment can lead to an excessive growth of insensitive microorganisms, including fungi.

Instructions

Retapamulin (Retapamulinum)