Altargo (Ointment) Instructions for Use

Marketing Authorization Holder

GlaxoSmithKline Trading, JSC (Russia)

Manufactured By

Glaxo Operations UK Limited (United Kingdom)

ATC Code

D06AX13 (Retapamulin)

Active Substance

Retapamulin (Rec.INN registered by WHO)

Dosage Form

Altargo

Ointment for external use 1%: tubes 5 or 15 g

Dosage Form, Packaging, and Composition

Excipients: white soft paraffin 0.99 g.

5 g – aluminum tubes (1) – cardboard packs.
15 g – aluminum tubes (1) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic for external use

Pharmacotherapeutic Group

Antimicrobial agent

Pharmacological Action

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

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

Data have shown that the binding center includes the ribosomal protein L3 and the zone of the ribosomal P center, as well as the peptidyl transferase center. By binding to this center, pleuromutilins inhibit peptidyl transfer, partially block interaction with the P center, and prevent the normal formation of active 50S ribosomal subunits, which leads to inhibition of bacterial cell protein synthesis through various mechanisms.

Due to its unique mechanism of action, cross-resistance between retapamulin and other classes of antibiotics against specific pathogens, according to in vitro studies, has been rare.

According to in vitro studies and clinical studies, Retapamulin is active against most strains of the main pathogens of skin and skin structure infections (Staphylococcus aureus and Streptococcus pyogenes). However, under clinical conditions, Retapamulin is less effective against some methicillin-resistant strains of Staphylococcus aureus.

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

Retapamulin has a predominantly bacteriostatic effect against the pathogens S. aureus and S. pyogenes.

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

Resistance

Due to its unique mechanism of action, cross-resistance between retapamulin and other classes of antibiotics against specific pathogens, according to in vitro studies, has been rare.

Retapamulin demonstrated a low potential for the development of resistance under in vitro conditions. The highest minimum inhibitory concentration value based on data from sequential passage of S. aureus and S. pyogenes in the presence of sub-minimal inhibitory concentrations (sub-MIC) of retapamulin was 2 µg/ml. During treatment with the drug throughout the clinical study program, the development of resistance to retapamulin was not observed.

Pharmacokinetics

Absorption

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

In most plasma samples from adult patients and children who received topical treatment with retapamulin twice a day for secondarily infected traumatic lesions, the drug concentration was below the limit of quantitation (0.5 ng/ml). The maximum detected concentration of retapamulin in adults was 10.7 ng/ml, and in children (aged 2-17 years) it was 18.5 ng/ml.

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

Concomitant use with ketoconazole

Concomitant use of oral ketoconazole at a dose of 200 mg twice daily against the background of daily topical application of 1% retapamulin ointment to damaged skin of healthy adult men increased the AUC_(0-24) and C_max of retapamulin by 81%. Concomitant use of retapamulin and CYP3A4 isoenzyme inhibitors (e.g., ketoconazole) in children has not been studied. Due to the low systemic absorption of the drug after its topical application in adults and children aged 2 years and older, no dose adjustment of retapamulin is required in these patients when co-administered with CYP3A4 isoenzyme inhibitors.

Distribution

The distribution of the drug in human tissues has not been studied. Retapamulin is approximately 94% bound to plasma proteins.

Metabolism

According to in vitro studies on human hepatocytes, the main metabolic pathways included mono-oxidation and di-oxidation. The main isoenzyme responsible for the metabolism of retapamulin in human liver microsomes is CYP3A4.

Excretion

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

Indications

Treatment of skin and skin structure infections caused by microorganisms susceptible to retapamulin, namely Staphylococcus aureus and Streptococcus pyogenes

• Primary impetigo;
• Secondarily infected traumatic lesions, for example, small cuts, abrasions, sutured wound edges;
• Secondarily infected dermatoses, including pustular psoriasis, complicated atopic and contact dermatitis.

ICD codes

Dosage Regimen

Altargo ointment should be applied in a thin layer to 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, the treatment should be reviewed.

The safety and efficacy of Altargo have not been studied in secondarily infected traumatic lesions longer than 10 cm or with a surface area greater than 100 cm, as well as in secondarily infected dermatoses or primary impetigo with a lesion area greater than 100 cm² (or more than 2% of the total body surface area in children).

Special patient groups

Children under 9 months of age

The safety and efficacy of retapamulin ointment in patients of this category have not been studied.

Elderly patients

Dose adjustment is not required.

Patients with renal impairment

Dose adjustment is not required. Given the low systemic absorption of retapamulin after topical application of the drug, it is unlikely that systemic concentrations will reach clinically significant levels in renal impairment.

Patients with hepatic impairment

Dose adjustment is not required. Given the low systemic absorption of retapamulin after topical application of the drug, it is unlikely that systemic concentrations will reach clinically significant levels in hepatic impairment.

Adverse Reactions

The adverse events listed below are presented according to the anatomical-physiological classification and frequency of occurrence. Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/ 100 and < 1 / 10), uncommon (≥ 1 /1 000 and < 1 /100), rare (≥ 1 / 10 000 and < 1 / 1 000), very rare (< 1/10 000, including isolated cases), unknown (cannot be estimated from the available data). Frequency categories were formed based on clinical studies of the drug and post-marketing surveillance.

Skin and subcutaneous tissue disorders

Uncommon: contact dermatitis.

General and local reactions (application site reactions)

Common: irritation.

Uncommon: pruritus, pain, erythema.

Post-marketing surveillance

Immune system disorders

Unknown: allergic reactions, including angioedema.

Contraindications

• Hypersensitivity to retapamulin or any other component of the ointment;
• Children under 9 months of age.

With caution since CYP3A4 isoenzyme inhibitors may further increase the systemic absorption of retapamulin, caution should be exercised when using CYP3A4 isoenzyme inhibitors concomitantly with retapamulin in young children.

Use in Pregnancy and Lactation

Fertility

The effect of retapamulin on fertility has not been established.

Pregnancy

The drug is not recommended due to insufficient experience with the use of retapamulin in pregnant women. The effect on the postnatal development of the child has not been assessed.

Lactation.

The safety of using retapamulin during lactation 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.

Use in Hepatic Impairment

Dose adjustment is not required. Given the low systemic absorption of retapamulin after topical application of the drug, it is unlikely that systemic concentrations will reach clinically significant levels in hepatic impairment.

Use in Renal Impairment

Dose adjustment is not required. Given the low systemic absorption of retapamulin after topical application of the drug, it is unlikely that systemic concentrations will reach clinically significant levels in renal impairment.

Pediatric Use

The safety and efficacy of retapamulin ointment in children under 9 months of age have not been studied.

Geriatric Use

Dose adjustment is not required.

Special Precautions

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

Do not apply to the eyes; Retapamulin has not been studied in ophthalmological practice.

Do not apply to mucous membranes; the efficacy and safety of applying retapamulin to mucous membranes have not been studied. Cases of epistaxis have been reported when retapamulin was applied to the nasal mucosa.

Do not take orally.

As with other antibiotics, prolonged use of retapamulin ointment may lead to the overgrowth of non-susceptible microorganisms, including fungi.

Effect on ability to drive vehicles and operate machinery

The drug does not affect the ability to drive vehicles and operate machinery.

Overdose

Symptoms

No cases of retapamulin overdose are known.

Treatment

Symptomatic treatment is indicated in the presence of any symptoms of overdose from topical application or accidental ingestion.

There is no specific antidote for the drug.

Drug Interactions

Clinically significant drug interactions in adults are unknown.

No studies on drug interactions in children have been conducted. Increased systemic absorption of retapamulin has been observed in children under 2 years of age.

Concomitant use of retapamulin and other topical agents on the same area of skin has not been studied and is not recommended.

Storage Conditions

Store at a temperature not exceeding 30°C (86°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.