Benoxiclin Topical Gel

This gel is for cutaneous use only. This is indicated for the topical treatment of mild to moderate acne vulgaris, particularly inflammatory lesions, in adults and adolescents aged 12 years and above.

Clindamycin inhibits bacterial protein synthesis by binding to 23S RNA of the 50S subunit of the bacterial ribosome. It impedes both the assembly of the ribosome and the translation process. The molecular mechanism through which this occurs is thought to be due to clindamycin's three-dimensional structure, which closely resembles the 3'-ends of L-Pro-Met-tRNA and deacylated-tRNA during the peptide elongation cycle - in acting as a structural analog of these tRNA molecules, clindamycin impairs peptide chain initiation and may stimulate dissociation of peptidyl-tRNA from bacterial ribosomes.

The peroxide bond of benzoyl peroxide is cleaved to form 2 benzoyloxy radicals.1 These radicals interact nonspecifically with bacterial proteins, interfering with their function, and survival of the bacteria. Over time, free radical interactions with bacterial proteins lead to decreased keratin and sebum around follicles. Benzoyl peroxide can also increase the turnover rate of epithelial cells, leading to skin peeling, and breaking down comedones.

Adults and Adolescents (aged 12 years and above): This gel should be applied once daily in the evening, to the entire affected area. Patients should be advised that excessive application will not improve efficacy, but may increase the risk of skin irritation. If excessive dryness or peeling occurs, frequency of application should be reduced or application temporarily interrupted. An effect on inflammatory and non-inflammatory lesions may be seen as early as week 2-5 of treatment. The safety and efficacy of this gel has not been studied beyond 12 weeks in acne vulgaris clinical trials. Treatment with this gel should not exceed more than 12 weeks of continuous use.

Paediatric population: The safety and efficacy of this gel has not been established in children under 12 years of age, therefore this gel is not recommended for use in this population.

Elderly patients: No specific recommendations. This gel should be applied in a thin film after washing gently with a mild cleanser and fully drying. If the gel does not rub into the skin easily, too much is being applied. Hands should be washed after application.

May enhance the action of neuromuscular blocking agents (e.g. atracurium). May antagonise the effects of parasympathomimetics. May competitively inhibit the effects of macrolides, ketolides, streptogramins, linezolid and chloramphenicol. Increased coagulation tests (prothrombin time/INR) and/or bleeding with vit K antagonists (e.g. warfarin, acenocoumarol, fluindione). PABA sunscreens may transiently discolour fabric.

Benzoyl Peroxide 5% & Clindamycin 1% gel must not be administered to patients with known hypersensitivity to clindamycin, lincomycin, benzoyl peroxide, any of the excipients.

Adverse drug reactions (ADRs) are summarised below for Benzoyl Peroxide 5% & Clindamycin 1% gel as a combination including any additional ADRs that have been reported for the single topical active ingredients, benzoyl peroxide or clindamycin. Adverse drug reactions are listed by MedDRA system organ class and by frequency. Frequencies are defined as: very common (³1/10); common (³1/100 and <1/10); uncommon (³1/1,000 and <1/100); rare (³1/10,000 and <1/1,000) and not known.

Immune system disorders: Allergic reactions including hypersensitivity and anaphylaxis; Not known.
Nervous system disorders: Paraesthesia; Uncommon.
Gastrointestinal disorders: Colitis (including pseudomembranous colitis), haemorrhagic diarrhoea, diarrhoea, abdominal pain; Not known.
Skin and subcutaneous tissue disorders: Erythema, peeling, dryness (Generally reported as ‘mild’ in severity); Very Common, Burning sensation; Common, Dermatitis, pruritus, erythematous rash, worsening of acne; Uncommon, Urticaria; Not known.
General disorders and Administration site conditions: Application site reactions including skin discoloration; Not known.

Pregnancy: There are no adequate data from the use of Benzoyl Peroxide 5% & Clindamycin 1% gel in pregnant women. Animal reproductive/developmental studies have not been conducted with Benzoyl Peroxide 5% & Clindamycin 1% gel or benzoyl peroxide. There are limited data on the use of clindamycin and benzoyl peroxide alone in pregnant women. Data from a limited number of pregnancies exposed in the first trimester to clindamycin indicate no adverse effects of clindamycin on pregnancy or on the health of the foetus/new-born child. Reproduction studies in rats and mice, using subcutaneous and oral doses of clindamycin, revealed no evidence of impaired fertility or harm to the foetus due to clindamycin. The safety of Benzoyl Peroxide 5% & Clindamycin 1% gel in human pregnancy is not established. Therefore, Benzoyl Peroxide 5% & Clindamycin 1% gel should only be prescribed to pregnant women after careful risk/benefit assessment by the physician in charge.

Breastfeeding: Use of Benzoyl Peroxide 5% & Clindamycin 1% gel has not been studied during breastfeeding. Percutaneous absorption of clindamycin and benzoyl peroxide is low however; it is not known whether clindamycin or benzoyl peroxide is excreted in human milk following the use of Benzoyl Peroxide 5% & Clindamycin 1% gel. Oral and parenteral administration of clindamycin has been reported to result in the appearance of clindamycin in breast milk. For this reason, Benzoyl Peroxide 5% & Clindamycin 1% gel should be used during lactation only if the expected benefit justifies the potential risk to the infant. To avoid accidental ingestion by the infant if used during lactation, Benzoyl Peroxide 5% & Clindamycin 1% gel should not be applied to the breast area.

Fertility: There are no data on the effect of Benzoyl Peroxide 5% & Clindamycin 1% gel on fertility in humans.

Contact with the mouth, eyes, lips, other mucous membranes or areas of irritated or broken skin should be avoided. Application to sensitive areas of skin should be made with caution. In case of accidental contact, rinse well with water. Benzoyl Peroxide 5% & Clindamycin 1% gel should be used with caution in patients with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis. Benzoyl Peroxide 5% & Clindamycin 1% gel should be used with caution in atopic patients, in whom further skin drying may occur. During the first weeks of treatment, an increase in peeling and reddening will occur in most patients. Depending upon the severity of these side effects, patients can use a non-comedogenic moisturiser, temporarily reduce the frequency of application of Benzoyl Peroxide 5% & Clindamycin 1% gel or temporarily discontinue use; however, efficacy has not been established for less than once daily dosing frequencies. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy may occur, which sometimes may be severe, especially with the use of peeling, desquamating, or abrasive agents. If severe local irritancy (e.g. severe erythema, severe dryness and itching, severe stinging/burning) occurs, Benzoyl Peroxide 5% & Clindamycin 1% gel should be discontinued. As benzoyl peroxide may cause increased sensitivity to sunlight, sunlamps should not be used and deliberate or prolonged exposure to sun should be avoided or minimised. When exposure to strong sunlight cannot be avoided, patients should be advised to use a sunscreen product and wear protective clothing. If a patient has sunburn, this should be resolved before using Benzoyl Peroxide 5% & Clindamycin 1% gel. If prolonged or significant diarrhoea occurs or the patient suffers from abdominal cramps, treatment with Benzoyl Peroxide 5% & Clindamycin 1% gel should be discontinued immediately, as the symptoms may indicate antibiotic-associated colitis. Suitable diagnostic methods, such as the determination of Clostridium difficile and toxin and, if necessary, colonoscopy should be employed and treatment options for colitis considered. The product may bleach hair or coloured fabrics. Avoid contact with hair, fabrics, furniture or carpeting.

Resistance to clindamycin: Patients with a recent history of systemic or topical clindamycin or erythromycin use are more likely to have pre-existing anti-microbial resistant Propionibacterium acnes and commensal flora.

Cross-resistance: Cross-resistance may occur with other antibiotics such as lincomycin and erythromycin when using antibiotic monotherapy.
Interaction with other medicinal products and other forms of interaction: No formal drug-drug interaction studies have been performed with Benzoyl Peroxide 5% & Clindamycin 1% gel. Concomitant topical antibiotics, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol and/or astringents, should be used with caution as a cumulative irritant effect may occur. Benzoyl Peroxide 5% & Clindamycin 1% gel should not be used in combination with erythromycin-containing products due to possible antagonism to the clindamycin component. Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore caution should be exercised with concomitant use. Concomitant application of Benzoyl Peroxide 5% & Clindamycin 1% gel with tretinoin, isotretinoin and tazarotene should be avoided since benzoyl peroxide may reduce their efficacy and increase irritation. If combination treatment is required, the products should be applied at different times of the day (e.g. one in the morning and the other in the evening). Using topical benzoyl peroxide-containing preparations at the same time as topical sulfonamide-containing products may cause skin and facial hair to temporarily change colour (yellow/orange).

Excessive application of Benzoyl Peroxide 5% & Clindamycin 1% gel may result in severe irritation. In this event, discontinue use and wait until the skin has recovered. Topically applied benzoyl peroxide is not generally absorbed in sufficient amounts to produce systemic effects. Excessive application of topically applied clindamycin may result in absorption of sufficient amounts to produce systemic effects. In the event of accidental ingestion of Benzoyl Peroxide 5% & Clindamycin 1% gel, gastrointestinal adverse reactions similar to those seen with systemically administered clindamycin may be seen.

Benzoyl peroxide, Azelaic acid & other preparations

Store in a refrigerator (2°-8°C), do not freeze. Do not store above 25°C after dispensing.