Indoxil gel, 25g

Indoxil is intended for topical use only.

The drug should be applied in a thin layer over the entire affected area 1 time / day after thorough cleansing of the skin with a mild cleanser and complete drying of 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, a moisturizer can be used after the gel has absorbed.

If dry skin or peeling occurs, reduce the frequency of using the gel or temporarily suspend treatment. The effectiveness of the drug with a frequency of use less than 1 time / day has not been studied.

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

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

The safety and efficacy of using a combination of clindamycin and benzoyl peroxide for the treatment of acne longer than 12 weeks has not been studied. The expected benefit to the patient should be carefully evaluated when prescribing treatment for more than 12 weeks of continuous use.

Special patient groups

The safety and efficacy of using a combination of clindamycin and benzoyl peroxide has not been studied for children under 12 years of age, therefore, the use of a combination of clindamycin and benzoyl peroxide is not recommended in this population.

There are no specific recommendations for elderly patients.

In patients with renal insufficiency, there is no need for dose adjustment. Since absorption of clindamycin and benzoyl peroxide through the skin is weak when applied topically, the effect of renal failure on the occurrence of clinically significant systemic exposure is unlikely.

In patients with hepatic impairment, there is no need for dose adjustment. Since absorption of clindamycin and benzoyl peroxide through the skin is weak when applied topically, the effect of hepatic failure on the occurrence of clinically significant systemic exposure is unlikely.

Gel for external use from white to yellowish, homogeneous.

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 amount of active substances can be adjusted depending on the purity of the batch of substances.

** during 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.

• 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. history.

  Carefully

• Concomitant use with other topical acne treatments should be carried out with caution due to the possible cumulative skin irritation, which can sometimes be severe, especially when using products with exfoliating or abrasive action. Indoxil should be used with caution if it is necessary to take it simultaneously with peripheral muscle relaxants.

pharmachologic effect

Mechanism of action

Clindamycin is an antibiotic of the lincosamide group that has a bacteriostatic effect against gram-positive aerobic microorganisms and a wide range of anaerobic bacteria. Lincosamides, such as clindamycin, bind to the 50S ribosome subunit of susceptible bacteria and prevent peptide chain elongation by interfering with the transport of ieptidil. 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 oxidant with bactericidal and mild keratolytic action. Benzoyl peroxide has a nonspecific bactericidal mechanism of action, forming reactive oxygen species that prevent the emergence of clindamycin-resistant microorganisms.

Pharmacodynamic effects

Clindamycin is active in vitro against Propionibacterium acnes, which cause acne. There is evidence of the possibility of developing P. acnes resistance to clindamycin. Clindamycin inhibits P. acnes in vitro (minimum inhibitory concentration (MIC) 0.4 ?g / ml). After application, clindamycin reduces the free fatty acid content 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 due 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 treating acne due to its anti-inflammatory and some keratolytic action.

Resistance and cross-resistance

Treatment of acne with antibiotics such as clindamycin and erythromycin for topical and oral administration, in the form of 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 can cause the development of resistance in these microorganisms.

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

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

Where possible, local resistance data should be considered, especially when treating serious infections.

Cross-resistance was found between clindamycin and lincomycin.

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 elements in patients who used topical clindamycin phosphate for 2 weeks.

There is no confirmation of systemic accumulation of clindamycin, as well as 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 percutaneous absorption of clindamycin.

Withdrawal

Clindamycin is excreted mainly 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.

Application during pregnancy and lactation

Pregnancy

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

There are limited data on the use of topical preparations containing one of the active ingredients (clindamycin or benzoyl peroxide) in pregnant women. 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 prescribed 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 a combination of clindamycin and benzoyl peroxide during breastfeeding.

Clindamycin and benzoyl peroxide have poor percutaneous absorption, but there are no data on the excretion of clindamycin or benzoyl peroxide when applied topically into breast milk. Clindamycin is excreted in 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.

In order to avoid accidental ingestion of the drug into the child's body when using it during lactation, the drug should not be applied to the breast skin.

Fertility

Reproductive effects of clindamycin or benzoyl peroxide for topical use are not available.

Application for violations of liver function

In patients with hepatic impairment, there is no need for dose adjustment.

Application for impaired renal function

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

Application in children

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

Use in elderly patients

There are no specific recommendations for elderly patients.

special instructions

Avoid getting the drug in the mouth, eyes, on the surface of the lips, other mucous membranes, as well as on irritated damaged areas of the skin. In case of accidental contact of the gel on the indicated areas, they should be thoroughly rinsed with water.

During the first week of treatment, most patients experience increased flaking 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 with a frequency of less than 1 time / day has not been studied.

If severe skin irritation occurs (for example, severe erythema, severe dry skin and itching, severe tingling / burning sensation), the drug should be discontinued.

Since benzoyl peroxide can cause hypersensitivity to sunlight, prolonged exposure to sunlight should be avoided and tanning beds should be avoided while the drug is being used. If exposure to the sun cannot be avoided, sunscreen skin care products and clothing that protect from the sun should be used.

If the patient has sunburn, the drug should be discontinued until the burns have healed.

The product can discolor hair and colored fabric. Avoid getting the drug on hair, fabric, furniture or carpets.

Pseudomembranous colitis

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

Although pseudomembranous colitis is unlikely to occur with topical application 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 consulted as symptoms may indicate the presence of colitis caused by taking an antibiotic.

Clindamycin resistance

Benzoyl peroxide reduces the likelihood of the appearance 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

Cross-resistance was found between clindamycin and lincomycin.

Clindamycin resistance is often associated with erythromycin resistance.

Influence on the ability to drive vehicles and use mechanisms

The negative effect of the drug on the ability to drive vehicles or mechanisms is unlikely.

Overdose

Symptoms: Excessive application of the drug can cause severe irritation. In such cases, stop using the drug until the signs of skin irritation disappear. When benzoyl is applied topically, peroxide is mainly absorbed in an amount insufficient to cause systemic effects. When an excessive amount of clindamycin is applied topically, it may be absorbed in an amount that can cause systemic effects. In case of accidental ingestion of a combination of clindamycin and benzoyl peroxide inside, undesirable reactions from the gastrointestinal tract may occur, similar to those that occur with parenteral use of clindamycin.

Treatment: Apply appropriate symptomatic treatment to relieve irritation caused by excessive application of the drug. Treatment in case of accidental ingestion of the drug should be carried out based on the clinical situation, or in accordance with the recommendations of the local National Poison Control Center, if available.

Drug interactions

Because clindamycin is antagonistic to erythromycin; Indoxil should not be used in combination with drugs containing erythromycin.

It has been established that clindamycin disrupts neuromuscular transmission and, therefore, can enhance the effect of peripheral muscle relaxants.

Avoid the combined use of a combination of clindamycin and benzoyl peroxide with tretinoin, isotretinoin and tazarotene, since benzoyl peroxide can reduce their effectiveness and increase skin irritation. If a combination treatment is necessary, drugs should be used at different times of the day (for example, one drug in the morning and another drug in the evening).

The use of topical preparations containing benzoyl peroxide at the same time as topical preparations containing sulfonamide may cause temporary discoloration of the skin and hair at the site of application (yellow or orange discoloration).