Clindamycin, adapalene, and benzoyl peroxide are used together in a fixed-dose combination product for topical treatment of acne vulgaris in adults and pediatric patients 12 years and older. Clindamycin is a lincosamide antibacterial, adapalene is a retinoid-like drug, and benzoyl peroxide is an oxidizing agent. Clindamycin and benzoyl peroxide have each been shown to have in vitro activity against C. acnes, an organism which has been associated with acne vulgaris. Benzoyl peroxide also has keratolytic effects. Adapalene modulates cell differentiation, keratinization, and inflammatory processes. Administration site reactions and skin irritation are the most common adverse effects. Photosensitivity may also occur; therefore sun exposure should be minimized during use.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-For topical use only. Not for oral, ophthalmic, or intravaginal use. Avoid the eyes, mouth, paranasal creases, mucous membranes, and areas of broke, eczematous, or sunburned skin.
-Cleanse the affected area gently prior to use with a cleanser. Rinse with warm water and pat skin dry.
-After the skin is dry, apply a thin layer to the affected area. One pea-sized amount should be enough to cover the entire face.
-Gently rub the gel into the affected area. It is important to spread the gel over the entire face.
-Wash hands after use as product may bleach hair or colored fabrics.
Hypersensitivity reactions, including anaphylaxis (anaphylactoid reactions or anaphylactic shock), angioedema, urticaria, blepharedema (eyelid edema), throat tightness, swelling of the face, and eczema have been associated with use of clindamycin; adapalene; benzoyl peroxide in postmarketing reports. If a serious hypersensitivity reaction occurs, discontinue treatment immediately and initiate appropriate therapy.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with clindamycin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Gram-negative folliculitis has also been noted in postmarketing reports with clindamycin; adapalene; benzoyl peroxide.
Photosensitivity may occur as clindamycin; adapalene; benzoyl peroxide may increase sensitivity to ultraviolet light. Application site stinging (13.6%), burning (13.6%), pain (13.6%), erythema (4.5%), dryness (xerosis) (4.1%), skin irritation (2.1%), exfoliation (1.7%), and dermatitis (1.2%) have also been reported. An application site reaction is most likely to occur during the first four weeks of treatment. Local tolerability increased during the first two weeks of treatment and decreased thereafter. Irritant and allergic contact dermatitis have been noted. Depending on the severity of skin irritation, instruct patients to use a moisturizer, reduce the frequency of application, or discontinue use of clindamycin; adapalene; benzoyl peroxide. Sunburn, blister, pruritus, skin hyperpigmentation, and skin hypopigmentation have been noted in postmarketing reports.
Abdominal pain and gastrointestinal disturbances have been noted in postmarketing reports with clindamycin; adapalene; benzoyl peroxide.
Clindamycin; adapalene; benzoyl peroxide is contraindicated in patients with a history of regional enteritis (Crohn's disease), antibiotic-associated colitis/pseudomembranous colitis, or ulcerative colitis. Diarrhea, bloody diarrhea, and colitis have been reported with the use of topical and systemic clindamycin. Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including clindamycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Apply clindamycin; adapalene; benzoyl peroxide only to affected areas; accidental exposure to unaffected skin may cause irritation. Avoid ocular exposure or contact with the mouth, paranasal creases, mucous membranes, and areas of broken (skin abrasion), eczema, or sunburn. Do not use waxing as a depilatory method on skin treated with clindamycin; adapalene; benzoyl peroxide. Avoid concomitant use of other potentially irritating topical products such as peeling, desquamating, or abrasive agents and products with high concentrations of alcohol, astringents, spices, or limes. Weather extremes, such as wind or cold, may be irritating to patients using clindamycin; adapalene; benzoyl peroxide.
Avoid sunlight (UV) exposure, including sunlamps and tanning beds, during treatment with clindamycin; adapalene; benzoyl peroxide. If sun exposure cannot be avoided, broad spectrum sunscreen products and physical sun blocks (protective clothing, hats) are recommended for protection of treated areas.
Available data with clindamycin; adapalene; benzoyl peroxide use in pregnancy are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted. In limited published clinical trials with pregnant persons, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproductive studies using systemic doses of clindamycin up to 192 times the maximum recommended human dose (MRHD) based on body surface area (BSA) comparisons revealed no evidence of fetal harm or teratogenicity. Available data from clinical trials with adapalene topical gel use in pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of adapalene during organogenesis at doses 64 and 128 times, respectively based on BSA, the MRHD resulted in fetal skeletal and visceral malformations. Dermal adapalene embryofetal development studies in animals at doses up to 6.0 mg/kg/day adapalene (up to 15 and 30 times the MRHD, respectively, based on a BSA comparison) exhibited no fetotoxicity and only minimal increases in skeletal variations. The systemic exposure of topical benzoyl peroxide is unknown. Based on published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Hence, maternal use is not expected to result in fetal exposure of the drug.
Due to the adapalene component, clindamycin; adapalene; benzoyl peroxide products should be used on the smallest area of skin and for the shortest duration possible while breast-feeding to minimize potential exposure to the breastfed infant. To avoid direct infant exposure, advise patients who are breast-feeding not to apply clindamycin; adapalene; benzoyl peroxide directly to the nipple and areola. If applied to the patient's chest, care should be taken to avoid infant exposure via direct contact with the infant skin. There are no data on the presence of clindamycin, adapalene or its metabolite, or benzoyl peroxide in human milk, the effects on the breastfed child, or the effects on milk production following topical administration. However, clindamycin has been reported to be present in human milk in small amounts following oral and parenteral administration. In animal studies, adapalene is present in rat milk following oral administration; it is possible that topical administration of large amounts of topical adapalene could result in sufficient systemic absorption to produce detectable quantities in human milk. Based on the published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Any amount of benzoyl peroxide excreted into human milk by a nursing mother would be expected to be rapidly metabolized by tissue and stomach esterases.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Cutibacterium acnes
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of acne vulgaris:
Topical dosage:
Adults: Apply a thin layer to the affected area once daily.
Children and Adolescents 12 to 17 years: Apply a thin layer to the affected area once daily.
Maximum Dosage Limits:
-Adults
1 application per day topically.
-Geriatric
1 application per day topically.
-Adolescents
1 application per day topically.
-Children
12 years: 1 application per day topically.
1 to 11 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Aminolevulinic Acid: (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
Benzalkonium Chloride; Benzocaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzocaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Benzocaine; Butamben; Tetracaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Calamine; Pramoxine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Ceftriaxone: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Clindamycin; Tretinoin: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Dapsone: (Minor) Coadministration of topical benzoyl peroxide-containing products with topical sulfone products, such as dapsone, may cause skin and facial hair to temporarily change color to a yellow/orange color.
Dibucaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Ethyl Chloride: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Fluocinolone; Hydroquinone; Tretinoin: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided. (Minor) Keratolytic agents or products that contain keratolytic agents, such as benzoyl peroxide, can potentiate the skin irritation caused by hydroquinone and hydroquinone-containing products. Also, concurrent use of topical hydroquinone and topical peroxide (e.g., benzoyl peroxide) on the same area of skin can result in transient dark staining of the skin due to oxidation of hydroquinone. Removal of staining can be accomplished by discontinuing concurrent use and by normal soap cleansing. Concurrent application of such agents should generally be avoided.
Halobetasol; Tazarotene: (Moderate) Concomitant use of tazarotene and dermatologic products containing benzoyl peroxide should be avoided. The manufacturer suggests that a patient's skin rest until the effects of such preparations subside before using tazarotene. When used together as part of acne therapy, these medications should be used separately at different times of the day to minimize skin irritation, unless directed otherwise by the prescriber. If skin irritation occurs, a decrease in dose or frequency of one or both agents may be necessary.
Hydrocortisone; Pramoxine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Hydroquinone: (Minor) Keratolytic agents or products that contain keratolytic agents, such as benzoyl peroxide, can potentiate the skin irritation caused by hydroquinone and hydroquinone-containing products. Also, concurrent use of topical hydroquinone and topical peroxide (e.g., benzoyl peroxide) on the same area of skin can result in transient dark staining of the skin due to oxidation of hydroquinone. Removal of staining can be accomplished by discontinuing concurrent use and by normal soap cleansing. Concurrent application of such agents should generally be avoided.
Isotretinoin: (Moderate) Benzoyl peroxide will cause additive irritant and drying effects with concomitant oral isotretinoin use. Reduction in the dose or temporary discontinuation of the benzoyl peroxide product may be needed until skin irritation resolves.
Lidocaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Lidocaine; Epinephrine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Lidocaine; Hydrocortisone: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Lidocaine; Menthol: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Lidocaine; Prilocaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Lidocaine; Tetracaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Menthol; Pramoxine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Methoxsalen: (Moderate) Use methoxsalen and adapalene together with caution; the risk of severe burns or phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Photosensitizing agents (topical): (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
Porfimer: (Major) Avoid coadministration of porfimer with adapalene due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like adapalene may increase the risk of a photosensitivity reaction. (Major) Avoid coadministration of porfimer with benzoyl peroxide due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like benzoyl peroxide may increase the risk of a photosensitivity reaction.
Pramoxine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Pramoxine; Zinc Acetate: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Salicylic Acid: (Moderate) Concomitant use of other potentially irritating topical products with adapalene should be done cautiously because of additive local irritation. Particular caution should be exercised in using adapalene in combination with preparations containing salicylic acid. If these preparations have been used, it is advisable not to start therapy with adapalene until the effects of such preparations in the skin have subsided. (Moderate) Concurrent use of benzoyl peroxide and topical products containing salicylic acid on the same area of skin will cause additive irritant and drying effects. Reduction in the dose or temporary discontinuation of the benzoyl peroxide product may be needed until skin irritation resolves. (Moderate) When concomitantly prescribed for acne therapy, apply salicylic acid and clindamycin topical solutions separately, at different times of the day to minimize skin irritation, unless directed otherwise by the prescriber. If skin irritation occurs, a decrease in dose or frequency of one or both agents may be necessary.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Concomitant use of other potentially irritating topical products with adapalene should be done cautiously because of additive local irritation. Particular caution should be exercised in using adapalene in combination with preparations containing salicylic acid. If these preparations have been used, it is advisable not to start therapy with adapalene until the effects of such preparations in the skin have subsided. (Moderate) Concurrent use of benzoyl peroxide and topical products containing salicylic acid on the same area of skin will cause additive irritant and drying effects. Reduction in the dose or temporary discontinuation of the benzoyl peroxide product may be needed until skin irritation resolves. (Moderate) When concomitantly prescribed for acne therapy, apply salicylic acid and clindamycin topical solutions separately, at different times of the day to minimize skin irritation, unless directed otherwise by the prescriber. If skin irritation occurs, a decrease in dose or frequency of one or both agents may be necessary.
Tazarotene: (Moderate) Concomitant use of tazarotene and dermatologic products containing benzoyl peroxide should be avoided. The manufacturer suggests that a patient's skin rest until the effects of such preparations subside before using tazarotene. When used together as part of acne therapy, these medications should be used separately at different times of the day to minimize skin irritation, unless directed otherwise by the prescriber. If skin irritation occurs, a decrease in dose or frequency of one or both agents may be necessary.
Tetracaine: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Topical Local Anesthetics: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
Tretinoin, ATRA: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Tretinoin; Benzoyl Peroxide: (Moderate) Benzoyl peroxide can potentiate the skin irritation caused by topical tretinoin. Concurrent application of these agents on areas treated with tretinoin should be avoided.
Trifarotene: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with adapalene is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like adapalene may increase the risk of a photosensitivity reaction. (Moderate) Use caution if coadministration of verteporfin with benzoyl peroxide is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like benzoyl peroxide may increase the risk of a photosensitivity reaction.
Mechanism of Action:-Clindamycin: Clindamycin, a lincosamide antibacterial, binds to the 23S RNA of the 50S ribosomal subunit of the bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, which inhibits protein synthesis. Clindamycin is bacteriostatic. The mechanism of action of clindamycin in treating acne vulgaris is unknown.
-Adapalene: Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.
-Benzoyl peroxide: Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects; however, the precise mechanism of action is unknown.
Clindamycin; adapalene; benzoyl peroxide is administered topically.
-Clindamycin: Clindamycin is metabolized to 2 bioactive metabolites, clindamycin sulfoxide and N-desmethylclindamycin, and various inactive metabolites. After oral dosage, only about 10% is excreted in the urine as active drug and metabolites, and about 3.6% in the feces. The remainder is excreted as inactive metabolites. The plasma half-life in adults with normal renal function is 2 to 3 hours.
-Adapalene: Excretion of adapalene appears to be primarily by the biliary route.
-Benzoyl peroxide: Benzoyl peroxide is converted to benzoic acid and eliminated in the urine.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP3A5
Clindamycin is metabolized primarily by CYP3A4, and to a lesser extent by CYP3A5. Drugs that are inhibitors or inducers of these enzymes may interact with clindamycin. In vitro studies have shown that clindamycin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1, or CYP2D6, and only moderately inhibits CYP3A4.
-Route-Specific Pharmacokinetics
Topical Route
Clindamycin; adapalene; benzoyl peroxide was evaluated in an open-label pharmacokinetic study in which patients applied 2.2 +/- 0.4 (mean +/- SD) grams of clindamycin; adapalene; benzoyl peroxide to the entire face (excluding eyes and lips), neck, upper chest, upper back and shoulders once daily for 28 days.
-Clindamycin: Clindamycin concentrations were measurable in the majority of samples after single and repeated topical administration. The mean Cmax was 2.44 ng/mL and the mean AUC was 30.7 ng x hr/mL on days 28 to 29, respectively. Clindamycin accumulated up to approximately 3-fold between days 1 to 2 and days 28 to 29 after once daily application.
-Adapalene: Adapalene concentrations were measurable in the majority of samples after single and repeated topical administration. The mean Cmax was 0.1 ng/mL and the mean AUC was 2.4 ng x hr/mL on days 28 to 29, respectively. Adapalene accumulated up to approximately 3-fold between days 1 to 2 and days 28 to 29 after once daily application.
-Benzoyl peroxide: Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid.