Duak

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DUAC (DUAC)

Composition:

Active substances: benzoyl peroxide anhydrous (in the form of aqueous benzoyl peroxide), clindamycin (in the form of clindamycin phosphate);

1 g of gel contains benzoyl peroxide anhydrous (in the form of aqueous benzoyl peroxide) 50 mg; clindamycin (in the form of clindamycin phosphate) 10 mg;

Excipients: carbomer, dimethicone, disodium lauryl sulfosuccinate, disodium edetate, glycerin, colloidal aqueous silica dioxide, poloxamer, sodium hydroxide, purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: homogeneous white or slightly yellowish gel.

Pharmacotherapeutic group. Topical agents for the treatment of acne. ATC code D10AF51.

Pharmacological Properties.

Pharmacodynamics

Clindamycin is a lincosamide antibiotic with bacteriostatic activity against gram-positive aerobic microorganisms and a broad spectrum of anaerobic bacteria. Lincosamides, such as clindamycin, bind to the 23S subunit of the bacterial ribosome and inhibit early stages of protein synthesis. The action of clindamycin is primarily bacteriostatic, although high concentrations may exert a slow bactericidal effect against susceptible strains.

Although clindamycin phosphate is inactive in vitro, rapid hydrolysis in vivo converts this compound into the bacterially active clindamycin. The antibacterial activity of clindamycin has been demonstrated clinically in the treatment of comedones in patients with acne at concentrations sufficient to be effective against most strains of Propionibacterium acnes. Clindamycin in vivo inhibits all tested cultures of Propionibacterium acnes (MIC = 0.4 µg/mL). Following application of clindamycin, the percentage of free fatty acids on the skin surface decreased from approximately 14% to 2%.

Benzoyl peroxide exerts a mild keratolytic effect on comedones at all stages of their development. It is an oxidizing agent with bactericidal activity against Propionibacterium acnes, the microorganism implicated in the development of acne vulgaris. In addition, it acts as a sebostatic agent, counteracting excessive sebum production associated with acne.

The addition of benzoyl peroxide reduces the potential for development of microorganisms resistant to clindamycin.

Pharmacokinetics

Percutaneous absorption of clindamycin is minimal. The presence of benzoyl peroxide in the formulation does not affect the percutaneous absorption of clindamycin. Radiolabeling studies have shown that percutaneous absorption of benzoyl peroxide is possible only after its conversion to benzoic acid. Benzoic acid is predominantly conjugated to form hippuric acid, which is excreted by the kidneys.

Clinical characteristics.

Indications.

Topical treatment of acne (acne vulgaris) of mild to moderate severity, predominantly inflammatory lesions, in adults and children aged 12 years and older.

Contraindications.

Hypersensitivity to the components of the drug or to lincomycin. Regional enteritis, ulcerative colitis, or antibiotic-associated colitis (including pseudomembranous colitis), either present or with history of such conditions. Pediatric age under 12 years.

Interaction with other medicinal products and other forms of interactions.

No studies on drug interactions have been conducted.

Clindamycin/benzoyl peroxide should not be used in combination with products containing erythromycin due to the potential antagonism with clindamycin.

Clindamycin has been shown to have neuromuscular blocking properties that may potentiate the effect of other neuromuscular blocking agents. Therefore, clindamycin/benzoyl peroxide should be used with caution in patients receiving such agents.

Concomitant use of clindamycin/benzoyl peroxide with tretinoin, isotretinoin, and tazarotene should be avoided, as benzoyl peroxide may reduce their efficacy and increase irritation. If combination therapy is necessary, the products should be applied at different times of the day (e.g., one in the morning, the other in the evening).

Concurrent use of benzoyl peroxide-containing products and topical sulfonamide-containing products may cause temporary discoloration of the skin and hair (yellow/orange).

When used concomitantly with topical antibiotics, medical, regular, or abrasive soaps, and cosmetic products with drying effects, as well as products with high concentrations of alcohol and/or astringents, a cumulative irritant effect may occur.

Special precautions for use

Avoid contact with the eyes, mouth, lips, other mucous membranes, or areas of irritated or damaged skin. In case of accidental contact, rinse thoroughly with water.

During the first weeks of treatment, increased skin desquamation and redness may occur in most patients. Depending on the severity of these adverse effects, patients may use a moisturizer, temporarily reduce the frequency of application of clindamycin/benzoyl peroxide, or temporarily discontinue treatment. However, the efficacy of applying the product less than once daily has not been established.

Concomitant use of other topical acne treatments should be performed with caution due to the potential for cumulative irritation, which may sometimes be severe, particularly when desquamative or abrasive ingredients are used.

If severe local irritation occurs (e.g., severe erythema, dryness or pruritus, intense stinging/burning), treatment with clindamycin/benzoyl peroxide should be discontinued.

Benzoyl peroxide may increase sensitivity to sunlight. Therefore, avoid using ultraviolet lamps and minimize or avoid exposure to sunlight. If significant sun exposure cannot be avoided, patients should be advised to use sun-protective measures such as sunscreen and protective clothing.

If a patient has sunburn, it should be fully healed before initiating treatment with clindamycin/benzoyl peroxide.

The product may bleach hair and colored or dyed fabrics. Avoid contact with hair, textiles, furniture, or carpets.

Pseudomembranous colitis

Cases of pseudomembranous colitis have been reported with nearly all antibacterial agents, including clindamycin, with severity ranging from mild to life-threatening, and onset occurring even several weeks after discontinuation of therapy. Although this is highly unlikely with topical use of clindamycin/benzoyl peroxide, if a patient develops persistent and severe diarrhea or abdominal cramps, treatment should be discontinued immediately and further evaluation initiated, as these symptoms may indicate antibiotic-associated colitis.

Clindamycin resistance

Benzoyl peroxide reduces the potential for emergence of clindamycin-resistant microorganisms. However, patients with recent systemic or topical use of clindamycin or erythromycin may already harbor clindamycin-resistant strains of Propionibacterium acnes and resistant commensal flora.

Cross-resistance

Cross-resistance between clindamycin and lincomycin has been demonstrated.

Resistance to clindamycin is often associated with inducible resistance to erythromycin (see section "Interaction with other medicinal products and other forms of interaction").

Use during pregnancy or breastfeeding

Fertility

There are no data on the effect of topical clindamycin or benzoyl peroxide on human fertility.

Pregnancy

There are insufficient data on the use of the gel in pregnant women. Reproductive toxicity and embryofetal developmental studies in animals have not been conducted with the gel or with benzoyl peroxide alone. Limited data are available on the use of clindamycin or benzoyl peroxide alone during pregnancy. Observational data from a limited number of pregnancies exposed during the first trimester suggest no adverse effects of clindamycin on pregnancy or fetal/neonatal health.

Reproductive toxicity studies in animals following oral and subcutaneous administration of clindamycin did not show impaired fertility or adverse effects on the fetus.

The safety of using the gel in pregnant women has not been established.

Therefore, during pregnancy, the physician may prescribe the product only if the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding

Clinical studies on the topical use of clindamycin/benzoyl peroxide during breastfeeding have not been conducted. Percutaneous absorption of clindamycin/benzoyl peroxide is low; it is unknown whether clindamycin or benzoyl peroxide is excreted in breast milk following topical application. However, clindamycin has been reported to be present in breast milk after oral and parenteral administration.

Therefore, during breastfeeding, the physician may prescribe the product only if the expected benefit to the mother outweighs the potential risk to the infant.

To avoid accidental ingestion of Duac gel by an infant when used by the mother during lactation, the gel should not be applied to the breast area.

Ability to affect reaction speed when driving or operating machinery

No studies have been conducted to assess such effects. Given the product's adverse reaction profile, a negative impact is not expected.

Method of Administration and Dosage

For external use only.

Adults and children aged 12 years and older.

Duac should be applied once daily in the evening to affected areas after thoroughly cleansing the skin with water and drying it. If the gel does not spread easily on the skin, this indicates an excessive amount has been applied.

Hands should be washed after applying the gel. The patient may use a moisturizer if needed.

If excessive dryness or peeling of the skin occurs, the frequency of application should be reduced or treatment should be temporarily discontinued. Efficacy has not been established when the gel is applied less frequently than once daily. The gel should not be used more than once a day.

Patients should be advised that increasing the amount of gel applied does not enhance therapeutic effectiveness but increases the risk of skin irritation.

Therapeutic effect may take from 2 to 5 weeks of treatment. The maximum duration of treatment is 12 weeks.

Children

Do not use in children under 12 years of age.

Overdose

Excessive topical application of clindamycin/benzoyl peroxide may cause severe skin irritation. In such cases, treatment should be discontinued and healing of irritation awaited.

When applied topically, benzoyl peroxide is generally not absorbed in amounts sufficient to cause systemic effects.

Excessive topical application of clindamycin may result in absorption in amounts sufficient to cause systemic effects.

In case of accidental oral ingestion, adverse reactions from the gastrointestinal tract may occur, similar to those observed with systemic use of clindamycin.

In case of excessive topical application, appropriate symptomatic measures should be taken to alleviate irritation symptoms. In case of accidental oral ingestion, appropriate clinical management should be provided.

Adverse reactions.

Adverse reactions are presented in a summarized manner based on experience with the combination and with individual active substances of the medicinal product – benzoyl peroxide and clindamycin. Adverse reactions are listed according to the MedDRA classification system and by frequency (see Table 1). Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); and not known (cannot be estimated from available data).

Table 1. Adverse reactions associated with the use of the active substances of the medicinal product – benzoyl peroxide and clindamycin.

*At the site of application.

**Based on post-marketing surveillance data. Since these observations cover populations of unknown size and include mixed factors, it is not possible to reliably estimate their frequency; however, systemic reactions were observed rarely.

In addition to the adverse reactions listed in the table above, phototoxic reactions at the site of application were frequently observed in the main clinical trial using topical clindamycin 1%/benzoyl peroxide 3% gel.

Local tolerability

Based on data from 5 clinical trials using Duac gel, all patients were classified according to the degree of erythema, desquamation, burning sensation, and dryness using the following scale: 0 – absent, 1 – mild, 2 – moderate, 3 – severe. The percentage of patients exhibiting symptoms before and during treatment is presented in Table 2.

Table 2. Local tolerability of Duac gel when applied once daily in patients (n=397) participating in phase 3 of the clinical trial.

Shelf life.

1.5 years.

Shelf life after first opening of the tube – 2 months.

Storage conditions.

Keep out of reach of children. Store in a refrigerator (2–8 °C). Do not freeze.

Storage conditions after first opening of the tube.

Keep out of reach of children at a temperature not exceeding 25 °C.

Packaging.

15 g, 25 g, or 30 g in a tube, 1 tube per cardboard box.

Supply category. Over-the-counter (without prescription).

Manufacturer.

Glaxo Operations UK Limited, United Kingdom.

Glaxo Operations UK Limited, United Kingdom.

Manufacturer's address and place of business.

Glaxo Operations UK Limited, Harmire Road, Barnard Castle, DL12 8DT, United Kingdom.

Glaxo Operations UK Limited, Harmire Road, Barnard Castle, DL12 8DT, United Kingdom.