Altargo® (Altargo®)

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Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceRetapamulinRetapamulin
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  • Altargo®
    ointment externally 
    GlaxoSmithKline Trading, ZAO     Russia
    • Dosage form: & nbspointment for external use
    Composition:

    On 1 g ointments:

    Name of components

    Quantity,% (m / m)

    Amount, g

    The current substance



    Retapamulin Crushed

    1,0

    0,01

    Excipient



    Paraffin soft white *

    99,0

    0,99

    * Paraffin soft white (European Pharmacopoeia) is a synonym for white petroleum jelly (American Pharmacopoeia).

    Description:White with a yellowish or grayish hue homogeneous ointment.
    Pharmacotherapeutic group:Antimicrobial agent
    ATX: & nbsp

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

    D.06.A.X.13   Retapamulin

    Pharmacodynamics:

    Mechanism of action

    Retapamulin is a semisynthetic derivative of pleuromutilin, which is isolated by fermentation from Clitopilus passeckerianus.

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

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

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

    Besides, retapamulin has activity in vitro in relation to some other gram-positive, gram-negative and anaerobic bacteria.

    Retapamulin has predominantly bacteriostatic action against pathogens Staphylococcus aureus and Staphylococcus pyogenes. The minimum bactericidal concentration (MBC) of retapamulin in relation to Staphylococcus aureus and Staphylococcus pyogenes exceeds the minimum inhibitory concentration (MIC) by 512-1024 times.

    The following data are available: in vitro, but their clinical significance is unknown: retapamulin is active against most isolates Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus viridans, Propionibacterium acnes, Peptostreptococcus spp., Prevotella spp., Fusohacterium 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 is rare.

    Reduced activity of pleuromouthlin in vitro is mediated by mutations of the ribosomal protein L3. The presence of the vgaAv variant of the AVC carrier reduces the activity of retapamulin in vitro. Susceptibility to pleuromutilins can also be reduced by Cfr pPHK methyltransferase, which forms the cross-resistance of staphylococci to phenicolam, lincosamides and streptogramin A.

    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 Staphylococcus aureus and Staphylococcus pyogenes in the presence of subminimal inhibitory concentrations (sub-MIC) of retapamulin was 2 μg / ml.During the treatment with rstapamulin during the program of the clinical study of the development of resistance to retapamulin was not observed.

    Pharmacokinetics:

    Suction

    In a study involving healthy adult participants, 1% retapamulin salve was applied daily to undamaged and damaged areas of the skin under the occlusive dressing for up to 7 days. Systemic absorption after external application of retapamulin through intact skin in healthy volunteers was very low. The highest value of the maximum concentration (Cmax), observed in the plasma of individual participants in the study after a single external application of 1% retapamulin ointment by 200 cm2 damaged skin, was 22.1 ng / ml.

    Each of 516 adult patients and children treated with retapamulin external treatment twice a day for the secondary infection of traumatic injuries, one sample of blood plasma was selected. In most plasma samples (89%), the concentration of the drug was below the limit of quantification (0.5 ng / ml). In the remaining samples (11%), the measurable retapamulin concentration in most cases (90%) was less than 2.5 ng / ml.The highest value of retapamulin concentration detected in adult plasma was 10.7 ng / ml, and children (age 2-17 years) 18.5 ng / ml.

    Children under 2 years

    In a study evaluating the pharmacokinetics of retapamulin for external use with children, plasma samples were obtained in patients aged 2 months to 2 years. 46% of the samples had a measurable concentration of retapamulin (0.52 to 177.3 ng / ml), with most samples (75%) having a rstapamuln concentration <5.0 ng / ml.

    Children from 2 to 9 months old

    In 69% of patients (n = 20), measurable concentrations of retapamulin in plasma were recorded. In four cases, the concentration of retapamulin in the plasma of this age group (26.9, 80.3, 174.3 and 177.3 ng / ml) exceeded the maximum retapamulin concentration recorded in children aged 2 to 17 years (18.5 ng / ml). Retapamulin not indicated for treatment of children younger than 9 months.

    Children from 9 months to 2 years

    In 32% of patients, measurable concentrations of retapamulin in plasma were recorded. In one case, the concentration of retapamulin in the plasma of this age group (18.5 ng / ml) exceeded the maximum retapamulin concentration recorded in children aged 2-17 years (18.5 ng / ml).

    Co-administration with ketoconazole

    The combined use of ketoconazole for oral administration at a dose of 200 mg twice daily and external application of retapamulin 1% ointment on the damaged skin of healthy adult males increased the mean values ​​of the area under the pharmacokinetic concentration-time curve (AUC (o-24)) and maximal concentration (Cmax) of retapamulin by 81%. The combined use of retapamulin and inhibitors of the isoenzyme CYP3A4 (eg, ketoconazole) in children has not been studied. In view of the low systemic absorption of retapamulin after its external use in adults and children aged 2 years and older, when combined with inhibitors of the isoenzyme CYP3A4, dosage adjustment of retapamulin is not required for these patients.

    Distribution

    The distribution of retapamulin in the tissues of the human body has not been studied.

    Retapamulin binds to plasma proteins approximately 94%.

    Metabolism

    Metabolism of retapamulin in the human body was investigated only using non-quantitative methods. In plasma of healthy participants of the study, two secondary monooxygenated metabolites were detected. Metabolites found in urine included two Ν-dimethylated metabolites, a large number of products of monooxygenation, as well as products of further oxidation.

    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 the isoenzyme CYP3A4. Very fresh amounts of three monooxygenated metabolites were found in freshly cut human skin samples.

    Excretion

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

    Indications:

    The drug Altargo® is indicated for the treatment of skin infections and its appendages caused by microorganism-sensitive microorganisms, 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 infected psoriasis, infected atopic and contact dermatitis.

    Contraindications:

    - Hypersensitivity in anamnesis or suspected of increased sensitivity to retapamulin or any other component included in the preparation;

    - Children's age up to 9 months.

    Carefully:Since inhibitors of the CYP3A4 isoenzyme can additionally increase the systemic absorption of retapamulin,When combined use of inhibitors of the isoenzyme CYP3A4 with retapamulin in young children should be careful.
    Pregnancy and lactation:

    Fertility

    In animal studies, the effect on the fertility of males or females was not associated with treatment.

    Pregnancy

    Appropriate clinical studies on the use of retapamulin in pregnant women have been conducted.

    Studies on animals showed little effect on fetal growth when taking the drug inside, the effect of the drug on the postnatal development of the calf was assessed.

    Retapamulin should be used during pregnancy only if the potential benefit to the mother is greater than the potential risk to the fetus associated with treatment.

    Breastfeeding period

    The safety of retapamulin application during breastfeeding was studied. During breastfeeding, the drug ns is recommended because of the lack of data on the penetration of the drug into breast milk.

    Dosing and Administration:

    Adults and children aged start 9 months

    Outwardly.

    The drug Altargo® it is necessary to apply a thin layer on the affected area of ​​the skin 2 once a day for 5 days.

    Ha a sterile bandage or gauze dressing can be applied if necessary.

    If there is no clinical effect during 3-4 days of diagnosis and treatment should be reviewed.

    Safety and efficacy of Altargo® have not been investigated in secondarily infected traumatic injuries longer than 10 cm or a surface area of ​​more than 100 cm2, as well as with secondarily infected dermatoses or primary impetigo with a lesion area of ​​more than 100 cm2 (or more 2% of the total surface of the body in children).

    Special patient groups

    Children younger 9 months

    Safety and efficacy of Altargo® patients of this category have not been studied.

    Elderly patients

    Correction of the dose is not required.

    Patients with impaired function of night

    Correction of the dose is not required. Given the low systemic absorption of retapamulin after external administration of the drug, it is not expected that if the renal function is compromised, the systemic concentration will reach a clinically significant level (see the section "Pharmacokinetics").

    Patients with impaired hepatic function

    Correction of the dose is not required.Given the low systemic absorption of retapamulin after external application of the drug, it is not expected that if the liver function is compromised, the systemic concentration will reach a clinically significant level (see the section "Pharmacokinetics").

    Side effects:

    The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥ 1/10), often (≥ 1/100 and <1/10), infrequently (≥ 1/1000 and <1/100), rarely (≥ 1/10000 and <1 / 1000), very rarely (<1/10000, including individual cases). Frequency categories were formed on the basis of large clinical studies of the drug and post-registration surveillance.

    Frequency of occurrence of undesirable reactions

    Clinical Trials Data

    General disorders and reactions at the site of application

    Often: irritation.

    Infrequent: itching, pain, erythema.

    Disturbances from the skin and subcutaneous tissues

    Infrequent: contact dermatitis.

    Post-Business Monitoring

    Immune system disorders

    Unknown: hypersensitivity, including angioedema.

    General disorders and reactions at the site of application

    Unknown: irritation in the place of application, including burning.

    Overdose:

    Symptoms

    There are no known cases of overdose of retapamulin.

    Treatment

    Symptomatic treatment is indicated in the presence of any symptoms of drug overdose during external application or accidental ingestion.

    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 drugs for external use on the same skin area has not been studied and is not recommended.
    Special instructions:

    In case of allergic reaction or expressed local irritation after application of the drug Altargo® treatment should be stopped, the remnants of the ointment removed from the skin, an alternative treatment for the 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 studied.There have been cases of nasal bleeding when applying retapamulin on the nasal mucosa.

    Do not take internally.

    As with other antibacterial drugs, prolonged use of Altargo® can lead to an excessive growth of insensitive microorganisms, including fungi.

    The sensitivity of antibiotics in vitro varies depending on the geographical region and over time, so when choosing antibacterial therapy, it is necessary to take into account local information on resistance.

    Effect on the ability to drive transp. cf. and fur:Pharmacological properties and profile of side effects of the drug Altargo do not imply a negative effect on the ability to drive vehicles and mechanisms.
    Form release / dosage:Ointment for external use, 1%.
    Packaging:For 5 grams, 15 grams in aluminum tubes with a screwed plastic cap. One tube with instructions for medical use is placed in a cardboard box.
    Storage conditions:

    Store at a temperature not exceeding 30 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001307
    Date of registration:29.11.2011
    Expiration Date:29.11.2016
    Date of cancellation:2016-11-15
    The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia
    Manufacturer: & nbsp
    Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO
    Information update date: & nbsp16.07.2017
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