Instructions Zerkalin Intensive gel tube 30 g
Composition
active ingredients: clindamycin (as clindamycin phosphate); benzoyl peroxide anhydrous (as benzoyl peroxide aqueous);
1 g of gel contains clindamycin (as clindamycin phosphate) 10 mg; benzoyl peroxide anhydrous (as benzoyl peroxide aqueous) 50 mg;
excipients: carbomer 980, dimethicone, disodium lauryl sulfosuccinate, disodium edetate, glycerin, colloidal silicon dioxide, poloxamer 182, sodium hydroxide 2N solution, purified water.
Dosage form
Gel.
Main physicochemical properties: homogeneous gel of white or slightly yellowish color with visible small particles.
Pharmacotherapeutic group: Dermatologicals: Topical acne products. ATC code: D10A F51.
Pharmacodynamics
Clindamycin is a lincosamide antibiotic with bacteriostatic activity against gram-positive aerobic microorganisms and a wide range 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 predominantly bacteriostatic, although high concentrations may have a slow bactericidal effect on susceptible strains.
Although clindamycin phosphate is inactive in vitro, rapid hydrolysis in vivo converts this compound to the antibacterially active clindamycin. The antibacterial activity of clindamycin has been demonstrated clinically in the treatment of comedones in patients with acne at levels sufficient to be active against most strains of Propionibacterium acnes. Clindamycin inhibits all Propionibacterium acnes cultures tested in vivo (MIC-0.4 μg/mL). After application of clindamycin, the percentage of free fatty acids on the skin surface decreased from approximately 14% to 2%.
Benzoyl peroxide has 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 responsible for the development of acne vulgaris. In addition, it is a sebostatic agent that counteracts the excessive production of sebum associated with acne.
The addition of benzoyl peroxide reduces the potential for the emergence of microorganisms resistant to clindamycin.
Pharmacokinetics
Percutaneous absorption of clindamycin is minimal. The presence of benzoyl peroxide in the formulation did not affect the absorption of clindamycin through the skin. Radiolabeling studies have shown that absorption of benzoyl peroxide through the skin is possible only after its conversion to benzoic acid. Benzoic acid is mainly conjugated to form hippuric acid, which is excreted by the kidneys.
Indication
For the topical treatment of mild to moderate acne (acne vulgaris), predominantly inflammatory, in adults and children aged 12 years and over.
Contraindication
Hypersensitivity to the components of the drug and lincomycin. Local enteritis, ulcerative colitis or antibiotic-associated colitis (including pseudomembranous colitis) or their presence in history. Children's age up to 12 years.
Interaction with other medicinal products and other types of interactions
Drug interaction studies have not been conducted.
Clindamycin/benzoyl peroxide should not be used in combination with drugs containing erythromycin due to possible antagonism with clindamycin.
Clindamycin has been shown to have neuromuscular blocking properties that may potentiate the effects of other neuromuscular blocking agents. Therefore, clindamycin/benzoyl peroxide should be used with caution in patients being treated with such agents.
Concomitant use of clindamycin/benzoyl peroxide with tretinoin, isotretinoin, and tazarotene should be avoided because benzoyl peroxide may reduce their effectiveness and increase irritation. If combination therapy is necessary, the drugs should be applied at different times of the day (e.g., one in the morning, one in the evening).
Concomitant use of benzoyl peroxide-containing preparations and topical sulfonamide-containing preparations may cause temporary discoloration of the skin and scalp (yellow/orange).
With the combined use of topical antibiotics, medical, regular or abrasive soaps and cosmetics that have a drying effect, as well as products with a high concentration of alcohol and/or astringents, a cumulative irritating effect is possible.
Application features
Avoid contact with eyes, mouth, lips, other mucous membranes and areas with irritation or damage to the skin. In case of accidental contact, rinse well with water.
Concomitant use of other topical acne medications should be done with caution due to the possible cumulative irritant effect, which can sometimes be severe, especially when using desquamative or abrasive ingredients.
If severe local irritation occurs (e.g. severe erythema, dryness or itching, severe stinging/burning), use of clindamycin/benzoyl peroxide should be discontinued.
Benzoyl peroxide may cause increased sensitivity to sunlight, therefore, the use of ultraviolet lamps should be avoided and exposure to sunlight should be avoided or minimized. If strong exposure to sunlight cannot be avoided, the patient should be advised to use sunscreen and protective clothing.
If the patient has sunburn, it should be treated before prescribing clindamycin/benzoyl peroxide.
The product may discolor hair and colored and dyed materials. Avoid contact with hair, fabrics, furniture or carpets.
Pseudomembranous colitis
Pseudomembranous colitis, which may range in severity from mild to life-threatening, has been reported with the use of nearly all antibacterial agents, including clindamycin, and may occur as early as several weeks after discontinuation of therapy. Although this is very unlikely with topical clindamycin/benzoyl peroxide, if a patient develops prolonged or severe diarrhea or abdominal cramps, treatment should be discontinued immediately and further evaluation should be performed, as these symptoms may be suggestive of antibiotic-associated colitis.
Clindamycin resistance
Benzoyl peroxide reduces the potential for the development of clindamycin-resistant organisms. However, patients with a history of recent systemic or topical use of clindamycin or erythromycin may already harbor antibiotic-resistant strains of Propionibacteriumacnes and commensal flora.
Cross-resistance
Cross-resistance between clindamycin and lincomycin has been demonstrated.
Resistance to clindamycin is often associated with induced resistance to erythromycin (see section 4.5).
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 no adequate data on the use of the gel in pregnant women. Animal studies on reproductive toxicity and the effects on embryo/fetal development of the gel or benzoyl peroxide separately have not been conducted. There are limited data on the use of clindamycin or benzoyl peroxide separately in pregnant women. Observational data on a limited number of pregnancies when the drug was used in the first trimester indicate no adverse effects of clindamycin on pregnancy or on the health of the fetus/newborn.
Animal reproductive toxicity studies with oral and subcutaneous administration of clindamycin revealed no evidence of impaired fertility or harmful effects on the fetus.
The safety of using the gel in women during pregnancy has not been established.
Therefore, during pregnancy, a doctor can prescribe the drug only if the expected benefit to the woman outweighs the potential risk to the child.
Breast-feeding
No clinical studies have been conducted with topical clindamycin/benzoyl peroxide during breastfeeding. However, it is known that percutaneous absorption of clindamycin/benzoyl peroxide is low; it is not known whether clindamycin or benzoyl peroxide is excreted in human milk after topical administration. However, clindamycin has been reported to be present in human milk after oral and parenteral administration.
Therefore, during breastfeeding, a doctor may prescribe the drug only if the expected benefit to the mother outweighs the potential risk to the child.
To avoid accidental ingestion of Zerkalin® Intensive gel by an infant when used by a mother during lactation, the gel should not be applied to the breast area.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted on this effect. Given the adverse reaction profile of the drug, no negative effects are expected.
Method of administration and doses
For external use only.
Adults and children aged 12 and over.
Zerkalin® Intensive is applied once a day in the evening to the affected areas after thorough cleansing, rinsing the skin with water and drying. If the gel does not rub into the skin easily, this indicates that it is being used in excessive amounts.
Hands should be washed after applying the gel. The patient may apply a moisturizer if necessary.
If excessive dryness or peeling of the skin occurs, the frequency of application should be reduced or treatment should be temporarily discontinued. The effectiveness of treatment has not been proven when used less than once a day. Do not apply the gel more than once a day.
It may take 2 to 5 weeks of treatment to achieve a therapeutic effect. The maximum course 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 the irritation should be allowed to heal.
When benzoyl peroxide is applied topically, it is generally not absorbed in sufficient amounts to cause systemic effects.
Excessive topical application of clindamycin may result in its absorption in quantities sufficient to produce systemic effects.
In case of accidental oral administration, gastrointestinal adverse reactions similar to those observed with systemic use of clindamycin are possible.
Appropriate symptomatic measures should be taken to reduce symptoms of irritation in the event of excessive topical application. In the event of accidental ingestion, appropriate clinical care should be provided.
Adverse reactions
Table 1 summarizes the adverse reactions observed with the combination and the active substances of the drug - benzoyl peroxide and clindamycin - separately. Adverse reactions are presented according to the MedDRA classification and by frequency (see Table 1). The frequency is defined as follows: very common (≥ 1/10); common (≥ 1/100 and < 1/10); uncommon (≥ 1/1000 and < 1/100); rare (≥ 1/10000 and < 1/1000) and unknown (cannot be estimated from the available data).
Table 1. Adverse reactions when using the active ingredients of the drug – benzoyl peroxide and clindamycin.
| MedDRA system organ class | Very often | Often | Infrequently | Unknown** |
| Immune system disorders | Allergic reactions, including hypersensitivity and anaphylaxis | | | |
| Nervous system disorders* | Paresthesia | | | |
| Gastrointestinal disorders | Colitis (including pseudomembranous colitis), haemorrhagic diarrhoea, diarrhoea, abdominal pain | | | |
| Skin and subcutaneous tissue disorders* | Erythema, desquamation, dryness (mainly reported as moderate intensity events) | Burning sensation | Contact dermatitis, pruritus, erythematous rash, acne exacerbation | Urticaria |
| General disorders and administration site conditions | Application site reactions, including discoloration | | | |
* At the site of application.
** Based on post-marketing surveillance data. Because these observations involve populations of unknown size and include confounding factors, it is not possible to reliably estimate their frequency, although systemic reactions were observed rarely.
In addition to the adverse reactions listed in Table 1, photosensitivity reactions at the application site were commonly observed in the pivotal clinical trial with topical clindamycin 1%/benzoyl peroxide 3% gel.
Local portability
In 5 clinical studies, all patients were classified according to the degree of erythema, scaling, burning sensation and dryness according to the following scale: 0 – no symptoms, 1 – mild, 2 – moderate, 3 – severe. The percentage of patients who had symptoms before and during treatment is presented in Table 2.
Table 2. Local tolerability of once-daily gel application in patients
(n = 397) who participated in a phase 3 clinical trial.
| Adverse reactions | Before treatment | During treatment |
| Weak degree | Moderate degree | Severe degree | Weak degree | Moderate degree | Severe degree |
| Erythema | 28% | 3% | 0 | 26% | 5% | 0 |
| Exfoliation | 6% | < 1% | 0 | 17% | 2% | 0 |
| Burning sensation | 3% | < 1% | 0 | 5% | < 1% | 0 |
| Dryness | 6% | < 1% | 0 | 15% | 1% | 0 |
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua/.
Expiration date
2 years.
The shelf life after first opening the tube is 2 months.
Storage conditions
Store in a refrigerator at 2–8 °C. After first opening, store at a temperature not exceeding 25 °C. Keep out of the reach of children.
Packaging
25 g or 30 g, or 50 g, or 60 g of gel in a tube, 1 tube in a cardboard box.
Vacation category
Without a prescription.
Producer
Jadran-Galensky Laboratories, Dr.
Location of the manufacturer and address of its place of business.
Svilno 20, 51000 Rijeka, Croatia.
