KLENZIT-CMS Adapalene / Clindamycin Phosphate 1mg / 10mg per g Topical Gel 15g
RXDRUG-DR-XY41165
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Adapalene Microspheres + Clindamycin Phosphate Gel is indicated for the topical treatment of acne vulgaris.
Dosage/Direction for Use
Adults: Adapalene Microspheres + Clindamycin Phosphate Gel is used in the topical treatment of mild to moderate acne where comedones, papules and pustules predominate. Adapalene Microspheres Plus Clindamycin Phosphate Gel is applied once daily at night to the skin that that has been cleansed and dried. Other topical preparations that may cause irritation should not be used concomitantly.
During the early weeks of therapy, an apparent exacerbation of acne may occur. This is due to the action of the medication on previously unseen lesions and should not be considered a reason to discontinue therapy. Therapeutic results should be noticed after eight to twelve weeks of treatment.
Pediatric population: The safety and efficacy of Adapalene Microspheres + Clindamycin Phosphate Gel in pediatric patients under the age of 12 years have not been established.
During the early weeks of therapy, an apparent exacerbation of acne may occur. This is due to the action of the medication on previously unseen lesions and should not be considered a reason to discontinue therapy. Therapeutic results should be noticed after eight to twelve weeks of treatment.
Pediatric population: The safety and efficacy of Adapalene Microspheres + Clindamycin Phosphate Gel in pediatric patients under the age of 12 years have not been established.
Overdosage
No overdosage has been reported with adapalene and clindamycin in human beings.
Contraindications
Adapalene Microspheres + Clindamycin Phosphate Gel is contraindicated in individuals with a history of hypersensitivity to preparations containing Clindamycin, Lincomycin, Adapalene or any of the components of the preparation, a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis.
Warnings
Clindamycin, when administered orally and parenterally, has been associated with ulcerative colitis, which may result in patient death. Use of the topical formulation of clindamycin results in the absorption of the antibiotic from the skin surface. Topical and systemic clindamycin have been reported to cause diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis).
Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.
Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.
Special Precautions
Cutaneous signs and symptoms such as erythema, dryness, scaling, burning or pruritus may be experienced during treatment.
Avoid contact with the eyes, lips, angles of the nose and mucous membranes.
Avoid excessive exposure to sunlight, including sunlamps.
Concomitant use of topical products that may dry or irritate the skin, such as medicated or abrasive soaps or cleansers, soaps, and cosmetics with a strong drying effect and products with concentrations of alcohol, astringents, spices or lime; local irritation may occur.
In case of hypersensitivity to any of the ingredients, discontinue the therapy.
Do not apply to cuts.
Avoid exposure to cuts, eczematous, sun-burnt or abraded skin.
Avoid exposure to UV light.
Exercise caution in atopic individuals.
Use in Children: The safety and efficacy of adapalene and clindamycin in pediatric patients under the age of 12 years has not been established. Hence, the use of Adapalene Microspheres + Clindamycin Phosphate Gel in patients under the age of 12 years is not recommended.
Avoid contact with the eyes, lips, angles of the nose and mucous membranes.
Avoid excessive exposure to sunlight, including sunlamps.
Concomitant use of topical products that may dry or irritate the skin, such as medicated or abrasive soaps or cleansers, soaps, and cosmetics with a strong drying effect and products with concentrations of alcohol, astringents, spices or lime; local irritation may occur.
In case of hypersensitivity to any of the ingredients, discontinue the therapy.
Do not apply to cuts.
Avoid exposure to cuts, eczematous, sun-burnt or abraded skin.
Avoid exposure to UV light.
Exercise caution in atopic individuals.
Use in Children: The safety and efficacy of adapalene and clindamycin in pediatric patients under the age of 12 years has not been established. Hence, the use of Adapalene Microspheres + Clindamycin Phosphate Gel in patients under the age of 12 years is not recommended.
Use In Pregnancy & Lactation
Pregnancy: Adapalene: Category C: No teratogenic effects were seen in animal studies. There are no adequate and well controlled studies in pregnant women with adapalene. Hence use of adapalene is not recommended during pregnancy. Adapalene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clindamycin: Category B: Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of Clindamycin. These studies revealed no evidence of fetal harm.
Lactation: It is not known whether Adapalene or Clindamycin is excreted in human milk following use of topical gel. However, orally and parenterally administered Clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue the use of Adapalene Microspheres + Clindamycin Phosphate Gel, taking into account the importance of the drug to the mother.
Clindamycin: Category B: Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of Clindamycin. These studies revealed no evidence of fetal harm.
Lactation: It is not known whether Adapalene or Clindamycin is excreted in human milk following use of topical gel. However, orally and parenterally administered Clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue the use of Adapalene Microspheres + Clindamycin Phosphate Gel, taking into account the importance of the drug to the mother.
Adverse Reactions
Some adverse effects such as erythema, scaling, dryness, pruritus and burning occur in 10-40% of patients. Pruritus or burning immediately after application also occurs frequently. In approximately 1% or less of patients, skin irritation, burning/stinging, erythema. sunburn and acne flares have also been reported. These are most commonly seen during the first month of therapy and decrease in frequency and severity thereafter. All adverse effects with the use of Adapalene and Clindamycin during clinical trials were reversible after discontinuation of therapy.
Drug Interactions
As Adapalene has the potential to produce local irritation in some patients, concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentration of alcohol, astringents, spices or lime) should be used with caution. Particular caution should be exercised in using preparations containing sulfur, resorcinol or salicylic acid in combination with Adapalene Microspheres + Clindamycin Phosphate Gel.
If these preparations have been used, it is advisable not to start therapy with Adapalene Microspheres + Clindamycin Phosphate Gel, until the effects of such preparations in the skin have subsided.
Clindamycin has neuromuscular blocking properties. Therefore, it should be used with caution in patients receiving neuromuscular agents as that may enhance the action of these neuromuscular blocking agents.
If these preparations have been used, it is advisable not to start therapy with Adapalene Microspheres + Clindamycin Phosphate Gel, until the effects of such preparations in the skin have subsided.
Clindamycin has neuromuscular blocking properties. Therefore, it should be used with caution in patients receiving neuromuscular agents as that may enhance the action of these neuromuscular blocking agents.
Storage
Store at temperatures not exceeding 30°C.
Action
Pharmacology: Pharmacodynamics: Adapalene: Adapalene is a retinoid-like compound for the treatment of acne vulgaris. It is a naphthoic derivative with a methoxyphenyl adamantyl side chain. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization, and inflammatory processes all of which represent important features in the pathology of acne vulgaris.
Adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cystolic receptor protein. It has been suggested that topical adapalene may normalize the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.
Clindamycin: Clindamycin acts by inhibiting the bacterial protein synthesis by binding to the 50S ribosomal subunit and inhibiting the process of peptide chain initiation. Clindamycin inhibited all tested Propionibacterium acnes cultures at a minimum inhibitory concentration (MIC) of 0.4 μg/mL, in vitro. Cross-resistance between clindamycin and erythromycin has been demonstrated.
Microsphere technology is believed to contribute towards reduced side effects, improved stability, increased elegance, and enhanced formulation flexibility without reducing the efficacy. Microspheres averaging 12 μg in diameter act like microscopic sponges, storing the active drug until its release is triggered by application to the skin surface. Absorption takes place in a time controlled manner that reduced the incidence and severity of skin irritation, it also protects from photo degradation, therefore contributes to the long term stability of active ingredients.
Pharmacokinetics: Adapalene: The pharmacokinetics of topical adapalene has not been extensively studied. Therapeutic effects of the drug usually appear within 8 to 12 weeks of initiation of treatment. The transdermal absorption of adapalene is low. Only trace amounts of the parent substance (<0.25 ng/mL) have been found in the plasma of acne patients following chronic topical application of adapalene gel in controlled clinical trials. Excretion appears to be primarily by the biliary route.
Absorption of Clindamycin when applied topically is 4% to 5%. Less than 0.04% of the total dose was excreted in the urine, following multiple doses of clindamycin.
Toxicology: Carcinogenesis, Mutagenesis and Impairment of Fertility: Carcinogenicity studies with adapalene have been conducted in mice (topical) and in rats (oral doses) at approximately 4 to 75 times the maximum human topical dose. In the oral study, positive linear trends were observed in the incidence of follicular cell adenomas and carcinomas in the thyroid glands of the female rats and in the incidence of benign and malignant phaeochromocytomas in the adrenal medullas of male rats.
No photocarcinogenicity studies have been performed with adapalene. Animal studies have shown an increased tumorigenic risk with the use of pharmacologically similar drugs (e.g. retinoids) when exposed to ultraviolet radiation or sunlight. Patients should therefore be advised to avoid or minimize exposure to either sunlight or artificial ultraviolet radiation sources.
In a series of in vitro and in vivo studies, adapalene did not exhibit mutagenic or genotoxic activity.
The carcinogenicity of a 1% clindamycin was evaluated by daily application for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin used, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.
Clindamycin (1%) caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight.
Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative. Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.
Adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cystolic receptor protein. It has been suggested that topical adapalene may normalize the differentiation of follicular epithelial cells resulting in decreased microcomedone formation.
Clindamycin: Clindamycin acts by inhibiting the bacterial protein synthesis by binding to the 50S ribosomal subunit and inhibiting the process of peptide chain initiation. Clindamycin inhibited all tested Propionibacterium acnes cultures at a minimum inhibitory concentration (MIC) of 0.4 μg/mL, in vitro. Cross-resistance between clindamycin and erythromycin has been demonstrated.
Microsphere technology is believed to contribute towards reduced side effects, improved stability, increased elegance, and enhanced formulation flexibility without reducing the efficacy. Microspheres averaging 12 μg in diameter act like microscopic sponges, storing the active drug until its release is triggered by application to the skin surface. Absorption takes place in a time controlled manner that reduced the incidence and severity of skin irritation, it also protects from photo degradation, therefore contributes to the long term stability of active ingredients.
Pharmacokinetics: Adapalene: The pharmacokinetics of topical adapalene has not been extensively studied. Therapeutic effects of the drug usually appear within 8 to 12 weeks of initiation of treatment. The transdermal absorption of adapalene is low. Only trace amounts of the parent substance (<0.25 ng/mL) have been found in the plasma of acne patients following chronic topical application of adapalene gel in controlled clinical trials. Excretion appears to be primarily by the biliary route.
Absorption of Clindamycin when applied topically is 4% to 5%. Less than 0.04% of the total dose was excreted in the urine, following multiple doses of clindamycin.
Toxicology: Carcinogenesis, Mutagenesis and Impairment of Fertility: Carcinogenicity studies with adapalene have been conducted in mice (topical) and in rats (oral doses) at approximately 4 to 75 times the maximum human topical dose. In the oral study, positive linear trends were observed in the incidence of follicular cell adenomas and carcinomas in the thyroid glands of the female rats and in the incidence of benign and malignant phaeochromocytomas in the adrenal medullas of male rats.
No photocarcinogenicity studies have been performed with adapalene. Animal studies have shown an increased tumorigenic risk with the use of pharmacologically similar drugs (e.g. retinoids) when exposed to ultraviolet radiation or sunlight. Patients should therefore be advised to avoid or minimize exposure to either sunlight or artificial ultraviolet radiation sources.
In a series of in vitro and in vivo studies, adapalene did not exhibit mutagenic or genotoxic activity.
The carcinogenicity of a 1% clindamycin was evaluated by daily application for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin used, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.
Clindamycin (1%) caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight.
Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative. Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.
MedsGo Class
Acne Treatment Preparations
Features
Brand
Klenzit - Cms
Full Details
Dosage Strength
1 mg / 10 mg per g (0.1% w/w / 1.0 w/w)
Drug Ingredients
- Adapalene
- Clindamycin
Drug Packaging
Topical Gel 15g
Generic Name
Adapalene / Clindamycin Phosphate
Dosage Form
Topical Gel
Registration Number
DR-XY41165
Drug Classification
Prescription Drug (RX)
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