Indoxyl 50 mg+10 mg/g gel for external use 25 g

Description

Gel for external use is white to yellowish in color, homogeneous.

Compound

1 g

benzoyl peroxide 66.7 mg,

which corresponds to the content of anhydrous benzoyl peroxide* 50 mg

clindamycin phosphate** 12.8 mg,

which corresponds to the content of clindamycin* 10 mg

* the amounts of active ingredients may be adjusted depending on the purity of the series of substances.

** in the production of clindamycin, phosphate is added with a 2% excess.

Excipients: carbomer - 20 mg, dimethicone - 1 mg, disodium lauryl sulfosuccinate - 0.4 mg, disodium edetate - 1 mg, glycerol - 40 mg, hydrated colloidal silicon dioxide - 2.5 mg, poloxamer 182 - 2 mg, sodium hydroxide - 3.1 mg, purified water - up to 1000 mg.

Package

15 g - aluminum tubes (1) - cardboard packs.

25 g - aluminum tubes (1) - cardboard packs.

pharmachologic effect

Mechanism of action

Clindamycin is an antibiotic of the lincosamide group with a bacteriostatic effect against gram-positive aerobic microorganisms and a wide range of anaerobic bacteria. Lincosamides, such as clindamycin, bind to the 50S ribosomal subunit of susceptible bacteria and, by interfering with eptidyl transport, prevent elongation of peptide chains. The action of clindamycin is mainly bacteriostatic, however, high concentrations may have a slow bactericidal effect against susceptible strains.

Although clindamycin phosphate is inactive in vitro, rapid hydrolysis in vivo converts this compound to active clindamycin.

Benzoyl peroxide is a highly lipophilic oxidizing agent with a bactericidal and weak keratolytic effect. Benzoyl peroxide has a nonspecific bactericidal mechanism of action, producing reactive oxygen species that prevent the emergence of clindamycin-resistant microorganisms.

Pharmacodynamic effects

Clindamycin is active in vitro against Propionibacterium acnes, which causes acne. There is evidence of the possibility of P. acnes developing resistance to clindamycin. Clindamycin inhibits P. acnes in vitro (minimum inhibitory concentration (MIC) 0.4 μg/ml). Once applied, clindamycin reduces free fatty acids on the skin surface from approximately 14% to 2%. Clindamycin reduces inflammation by inhibiting leukocyte chemotaxis.

The effectiveness of benzoyl peroxide in the treatment of acne is mainly attributed to its bactericidal activity, especially against P. acnes. The bactericidal activity of benzoyl peroxide is caused by the release of active or free oxygen radicals that can oxidize bacterial proteins. Benzoyl peroxide is effective in the treatment of acne due to its anti-inflammatory and some keratolytic effects.

Resistance and cross-resistance

Treatment of acne with topical and oral antibiotics such as clindamycin and erythromycin as monotherapy has been associated with the development of antimicrobial resistance in P. acnes as well as in saprophytic flora (eg, Staphylococcus aureus, Streptococcus pyogenes). Long-term use of clindamycin may cause the development of resistance in these microorganisms.

Benzoyl peroxide has a bactericidal effect and has not caused resistance in P. acnes. The inclusion of benzoyl peroxide in a combination formulation containing 1% clindamycin and 5% benzoyl peroxide reduced the number of clindamycin-resistant P. acnes organisms.

The level of acquired resistance for specific organisms may vary depending on geographic location and time.

Where possible, local resistance data should be taken into account, particularly when treating serious infections.

The presence of cross-resistance between clindamycin and lincomycin has been established.

Pharmacokinetics

Absorption, distribution and metabolism

Clindamycin phosphate undergoes rapid hydrolysis by skin phosphatases and is converted to clindamycin. Clindamycin is then metabolized to clindamycin sulfoxide. Significant concentrations of clindamycin were found in acne lesions in patients who used topical clindamycin phosphate for 2 weeks.

There is no evidence of systemic accumulation of clindamycin or accumulation of clindamycin in the skin after repeated use.

Clindamycin is metabolized in the liver to active and inactive metabolites.

Benzoyl peroxide is absorbed by the skin and metabolized to benzoic acid. When applied topically, less than 5% of the dose in the form of benzoic acid enters the systemic circulation.

The presence of benzoyl peroxide does not affect the transdermal absorption of clindamycin.

Removal

Clindamycin is excreted primarily in the urine in the form of the parent substance. T1/2 of clindamycin is about 9 hours. After repeated topical application of a gel containing clindamycin, less than 0.06% of the dose was excreted in the urine.

Benzoyl peroxide is excreted in the urine in the form of benzoic acid.

Indications

- acne (acne vulgaris) of mild to moderate severity, especially with a predominance of inflammatory skin lesions.

Dosage regimen

Indoxyl is intended for topical use only.

The drug should be applied in a thin layer to the entire affected area 1 time/day after thoroughly cleansing the skin with a mild cleanser and completely drying the skin.

The gel is poorly absorbed if an excessive amount of the drug is applied to the skin. After applying the gel, you should wash your hands.

If necessary, you can use a moisturizer after the gel is absorbed.

If dry skin or flaking occurs, you should reduce the frequency of use of the gel or temporarily suspend treatment. The effectiveness of the drug when used less than once a day has not been studied.

Applying the gel more frequently than recommended by the instructions does not increase the effectiveness of treatment, but may increase the risk of skin irritation.

The duration of treatment required to achieve a therapeutic effect is from 2 to 5 weeks, but not more than 12 weeks.

The safety and effectiveness of the combination of clindamycin and benzoyl peroxide in the treatment of acne lasting more than 12 weeks have not been studied. The expected benefit to the patient should be carefully assessed when prescribing treatment for more than 12 weeks of continuous use.

Special patient groups

The safety and effectiveness of the combination of clindamycin and benzoyl peroxide have not been studied in children under 12 years of age, and therefore the use of the combination of clindamycin and benzoyl peroxide is not recommended in this population.

There are no special recommendations for elderly patients.

In patients with renal failure, there is no need for dose adjustment. Because the absorption of clindamycin and benzoyl peroxide through the skin when applied topically is poor, renal impairment is unlikely to contribute to clinically significant systemic exposure.

In patients with liver failure, there is no need for dose adjustment. Because the absorption of clindamycin and benzoyl peroxide through the skin when applied topically is poor, hepatic impairment is unlikely to contribute to clinically significant systemic exposure.

Side effect

The adverse events presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and < 1/1,000), very rare (<1/10,000, including isolated cases). Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.

From the immune system:

rarely - allergic reactions, including hypersensitivity and anaphylactic reactions.

From the nervous system:

Uncommon: paresthesia in the area where the drug is applied.

From the digestive system:

rarely - colitis (including pseudomembranous colitis), hemorrhagic diarrhea, diarrhea, abdominal pain.

For the skin and subcutaneous fat:

very often - burning sensation, erythema, peeling, dry skin in the area where the drug is applied (these phenomena are mostly mild); often - photosensitivity in the area where the drug is applied; infrequently - itching, erythematous rash, dermatitis, worsening acne in the area of application of the drug; rarely - urticaria in the area where the drug is applied.

Other:

rarely - other reactions in the area of application, including hair bleaching.

In studies with topical use of clindamycin as monotherapy, headache and pain in the area of application of the drug were also frequently reported.

Local tolerance

Below are data regarding local tolerability of the drug in patients treated in clinical trials. The severity of local adverse effects was assessed according to the following scale: 0 - none, 1 - weak, 2 - moderate and 3 - severe local adverse effects.

The percentage of patients who had the following symptoms before treatment (baseline) and during treatment was as follows:

Before treatment (baseline) During treatment

Weak Moderate Severe Weak Moderate Severe

Erythema 28% 3% 0 26% 5% 0

Peeling 6% <1% 0 17% 2% 0

Burning 3% <1% 0 5% <1% 0

Dryness 6% <1% 0 15% 1% 0

Contraindications

- hypersensitivity to clindamycin, lincomycin, benzoyl peroxide and/or to any of the components of the drug;

- children under 12 years of age;

- lactation period;

- Crohn's disease, ulcerative colitis, pseudomembranous colitis, incl. in the anamnesis.

Carefully

Concomitant use with other topical acne treatments should be used with caution due to the potential for cumulative skin irritation, which can sometimes be severe, particularly when using products with exfoliating or abrasive properties.

Indoxyl should be used with caution if it is necessary to take it simultaneously with peripherally acting muscle relaxants.

Use during pregnancy and breastfeeding

Pregnancy

There have been no controlled studies in pregnant women using a topical gel containing a combination of clindamycin and benzoyl peroxide.

Data on the use of topical preparations containing one of the active ingredients (clindamycin or benzoyl peroxide) in pregnant women are limited. Preclinical studies do not confirm direct or indirect adverse effects that can be attributed to reproductive toxicity.

Given the low level of systemic exposure to clindamycin and benzoyl peroxide, adverse effects on pregnancy are unlikely. However, the combination of clindamycin and benzoyl peroxide should be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

Lactation period

There is no data on the safety of topical use of the combination of clindamycin and benzoyl peroxide during breastfeeding.

Clindamycin and benzoyl peroxide have poor percutaneous absorption, but there is no data on the excretion of clindamycin or benzoyl peroxide into breast milk when administered topically. Clindamycin is excreted into breast milk after oral and parenteral administration.

The combination of clindamycin and benzoyl peroxide should be used during lactation only if the expected benefit to the mother outweighs the potential risk to the baby.

To avoid accidental entry of the drug into the child’s body when using it during lactation, the drug should not be applied to the skin of the breast.

Fertility

There are no data regarding the reproductive effects of topical clindamycin or benzoyl peroxide.

Use for liver dysfunction

In patients with liver failure, there is no need for dose adjustment.

Use for renal impairment

In patients with renal failure, there is no need for dose adjustment.

Use in children

The use of the drug is contraindicated in children under 12 years of age.

Use in elderly patients

There are no special recommendations for elderly patients.

special instructions

Avoid getting the drug into the mouth, eyes, lips, other mucous membranes, as well as irritated damaged areas of the skin. If the gel accidentally gets into these areas, they should be rinsed well with water.

During the first week of treatment, most patients experience increased peeling and redness of the skin. Depending on the severity of these side effects, patients may use moisturizers, temporarily reduce the frequency of use of the drug, or temporarily discontinue use. The effectiveness of the drug when used less than once a day has not been studied.

If severe skin irritation occurs (eg, severe erythema, severe skin dryness and itching, severe tingling/burning), use of the drug should be discontinued.

Since benzoyl peroxide may cause increased sensitivity to sunlight, you should avoid prolonged exposure to sunlight and do not visit a solarium while using the drug. If sun exposure cannot be avoided, you should use sunscreen cosmetics for your skin and clothing that protects you from the sun's rays.

If the patient has sunburn, you should stop using the drug until the burns are healed.

The drug can discolor hair and colored fabric. Avoid contact of the drug with hair, fabric, furniture or carpeting.

Pseudomembranous colitis

Cases of pseudomembranous colitis have been reported with the use of almost all antibacterial agents, including clindamycin. Their severity varies in severity from mild to life-threatening. Pseudomembranous colitis may occur several weeks after discontinuation of therapy.

Although pseudomembranous colitis is unlikely to occur with topical use of a combination of clindamycin and benzoyl peroxide, if prolonged or severe diarrhea occurs or if the patient suffers from abdominal cramps, treatment should be stopped immediately and a doctor should be consulted, as symptoms may indicate the presence of colitis caused by pseudomembranous colitis. taking an antibiotic.

Resistance to clindamycin

Benzoyl peroxide reduces the likelihood of the emergence of microorganisms resistant to clindamycin. However, patients who have recently used parenteral or topical clindamycin or erythromycin are more likely to have propionobacteria and saprophytic flora with previously acquired antimicrobial resistance.

Cross resistance

The presence of cross-resistance between clindamycin and lincomycin has been established.

Resistance to clindamycin is often associated with resistance to erythromycin.

Impact on the ability to drive vehicles and operate machinery

A negative effect of the drug on the ability to drive vehicles or operate machinery is unlikely.

Overdose

Symptoms:

applying excessive amounts of the drug may cause severe irritation. In such cases, stop using the drug until signs of skin irritation disappear. When applied topically, benzoyl peroxide is primarily absorbed in amounts insufficient to cause systemic effects. If excessive amounts of clindamycin are administered topically, it may be absorbed in amounts that can cause systemic effects. If the combination of clindamycin and benzoyl peroxide is accidentally ingested, adverse reactions from the gastrointestinal tract may occur, similar to the adverse reactions that occur with parenteral use of clindamycin.

Treatment:

Appropriate symptomatic treatment is used to relieve irritation caused by the application of excessive amounts of the drug. Treatment for accidental ingestion should be based on the clinical situation or in accordance with the recommendations of the local National Poison Control Center, if available.

Drug interactions

Because clindamycin exhibits antagonism with erythromycin; Indoxyl should not be used in combination with drugs containing erythromycin.

Clindamycin has been shown to interfere with neuromuscular transmission and, therefore, may enhance the effect of peripherally acting muscle relaxants.

The combination of clindamycin and benzoyl peroxide with tretinoin, isotretinoin and tazarotene should be avoided as benzoyl peroxide may reduce their effectiveness and increase skin irritation. If combination treatment is necessary, the drugs should be administered at different times of the day (for example, one drug in the morning and another drug in the evening).

Using topical products containing benzoyl peroxide concomitantly with topical products containing a sulfonamide may cause a temporary change in the color of the skin and hair at the site of application (yellow or orange).

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature of 2-8°C; do not freeze. Shelf life: 2 years. Do not use after the expiration date stated on the package.

The opened tube should be stored at a temperature not exceeding 25°C for 2 months.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Indoxyl

Mechanism of action

Clindamycin is an antibiotic of the lincosamide group with a bacteriostatic effect against gram-positive aerobic microorganisms and a wide range of anaerobic bacteria. Lincosamides, such as clindamycin, bind to the 50S ribosomal subunit of susceptible bacteria and, by interfering with peptidyl transport, prevent elongation of peptide chains. The action of clindamycin is mainly bacteriostatic, however, high concentrations may have a slow bactericidal effect against sensitive strains.

Although clindamycin phosphate is inactive in vitro,

rapid hydrolysis
in vivo
converts this compound to active clindamycin.

Pharmacodynamic effects

Clindamycin is active in vitro

against propionobacterium
(Propionibacterium acnes),
which causes acne.
P. acnes
may develop resistance to clindamycin.

Clindamycin inhibits P. acnes in vitro

(minimum inhibitory concentration (MIC) 0.4 μg/ml).

Once applied, clindamycin reduces free fatty acids at the skin surface from approximately 14% to 2%.

Clindamycin reduces inflammation by inhibiting leukocyte chemotaxis.

The effectiveness of benzoyl peroxide in the treatment of acne is mainly attributed to its bactericidal activity, especially against P. acnes.

The bactericidal activity of benzoyl peroxide is caused by the release of active or free oxygen radicals that can oxidize bacterial proteins. Benzoyl peroxide is effective in the treatment of acne due to its anti-inflammatory and some keratolytic effects.

Resistance and cross-resistance

Treatment of acne with topical and oral antibiotics such as clindamycin and erythromycin as monotherapy has been associated with the development of antimicrobial resistance in P. acnes.

as well as in saprophytic flora (for example,
Staphylococcus aureus, Streptococcus pyogenes).
Long-term use of clindamycin may cause the development of resistance in these microorganisms.

Benzoyl peroxide has a bactericidal effect and has not caused resistance in P.
acnes.
The inclusion of benzoyl peroxide in a combination preparation containing 1% clindamycin and 5% benzoyl peroxide reduced the number of clindamycin-resistant
P. acnes organisms.
The level of acquired resistance for specific organisms may vary depending on geographic location and time.

Where possible, local resistance data should be taken into account, particularly when treating serious infections.

The presence of cross-resistance between clindamycin and lincomycin has been established.