Tretinoin; benzoyl peroxide is a topical combination product indicated for the treatment of acne vulgaris in adults and pediatric patients 9 years of age and older. Tretinoin is a naturally occurring retinoid and metabolite of vitamin A. Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects. The drug is administered topically to affected area(s) once daily; ensure precautions are taken to avoid contact with eyes, lips, paranasal creases, and mucous membranes. Skin irritation can occur with treatment. Depending on skin irritation severity, the irritation may be alleviated with the use of moisturizers, by decreasing the dosing frequency, or by discontinuing use of the product. Inform patients that tretinoin; benzoyl peroxide may increase sensitivity to ultraviolet light. Instruct patients to minimize or avoid exposure to both natural and artificial sunlight (e.g., tanning beds, UVA/B treatments).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-Tretinoin is classified as a hazardous drug.
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Topical Administration
-For external use only.
Cream/Ointment/Lotion Formulations
-Clean and dry the skin before applying.
-Apply a thin layer to the affected area(s).
-Avoid contact with the eyes, lips, paranasal creases, and mucous membranes.
-May stain or bleach hair or colored fabric. Wash hands after the application.
Recipients of tretinoin; benzoyl peroxide can experience application site reactions. These reactions may be alleviated through the use of moisturizers, by reducing the dosing frequency, or by discontinuing treatment. In clinical trials involving 555 patients who received tretinoin; benzoyl peroxide for facial acne vulgaris, the following application site reactions were observed: stinging, burning, or pain (10.6%), xerosis (4.9%), skin exfoliation (4.1%), erythema (4%), dermatitis (1.3%), pruritus (1.3%), and skin irritation (1.1%). In a majority of these cases, the adverse reaction was categorized as mild in severity. Local tolerability scores for erythema, scaling, dryness, itching, burning, and stinging increased during the first 2 weeks of treatment and decreased thereafter.
Hypersensitivity reactions, including anaphylaxis or anaphylactoid reactions, angioedema, and urticaria, have been reported with use of benzoyl peroxide containing products. If a serious hypersensitivity reaction occurs during treatment with tretinoin; benzoyl peroxide, immediately discontinue use of the drug and start appropriate therapy.
Use of tretinoin-containing products is associated with increased photosensitivity. Patients should avoid both natural and artificial sunlight while receiving tretinoin; benzoyl peroxide. If sun exposure cannot be avoided, patients should implement protective measures (e.g., sunscreen, loose-fitting clothing). Patients with a sunburn should not use topical tretinoin products until fully recovered.
Tretinoin; benzoyl peroxide topical cream is for external use only. Ensure steps are taken to avoid accidental ocular exposure or exposure to mucosal membranes, including handwashing after application of the cream.
Treatment with tretinoin; benzoyl peroxide may increase sensitivity to ultraviolet (UV) light. Minimize or avoid sunlight (UV) exposure, including both natural or artificial sunlight (i.e., tanning beds, UVA/B treatment), while using tretinoin; benzoyl peroxide. When sun exposure cannot be avoided, instruct patients with implement sun protection measures (e.g., sunscreen, loose-fitting clothes). Immediately discontinue treatment in patients who develop a sunburn while receiving tretinoin; benzoyl peroxide.
There are no data regarding the use of tretinoin; benzoyl peroxide during human pregnancy. Studies conducted with topical benzoyl peroxide have not demonstrated systemic absorption; thus, maternal use of the drug is not expected to result in fetal exposure to benzoyl peroxide. For topical tretinoin alone, available data from published observational studies in pregnant women have not established a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. However, there are reports of major birth defects with maternal use of topical tretinoin during the first trimester that are similar to those observed in infants exposed to oral retinoids, but these case reports do not establish a pattern or association with tretinoin-related embryopathy. In animal studies, tretinoin has been found to be both teratogenic and fetotoxic when administered either orally or topically in doses that exceed the maximum recommended human dose (MRHD) based on body surface area (BSA) and assuming 100% absorption; doses were 5 times the MRHD in rats and 100 times the MRHD in cynomolgus monkeys.
There are no data regarding the presence of tretinoin, benzoyl peroxide, or their metabolites in human milk. Further, it is unknown if these drugs adversely effect the breast-fed infant or milk production. Very little benzoic acid is absorbed systemically with topical use of benzoyl peroxide; therefore, minimal risk to the infant would be expected. It is not known if topically administered tretinoin could result in sufficient systemic absorption to produce detectable concentrations in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Avoid applying tretinoin; benzoyl peroxide topical cream to skin abrasion or cuts, sunburnt skin, or areas of eczema. Treatment may result in application site dryness, pain, exfoliation, erythema, dermatitis, pruritus, and irritation. Depending on the severity of these dermatologic reactions, instruct patients to use moisturizers, reduce frequency of the applications, or discontinue use of the drug.
For the treatment of acne vulgaris:
Topical dosage:
Adults: Apply a thin layer of cream topically to the affected area(s) once daily.
Children and Adolescents 9 years and older: Apply a thin layer of cream topically to the affected area(s) once daily.
Maximum Dosage Limits:
-Adults
1 application per day topically.
-Geriatric
1 application per day topically.
-Adolescents
1 application per day topically.
-Children
9 years and older: 1 application per day topically.
1 to 8 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
Adapalene; 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.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Atenolol; Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Azilsartan; Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
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.
Benzoyl Peroxide; Clindamycin: (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.
Benzoyl Peroxide; Erythromycin: (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.
Benzoyl Peroxide; Sulfur: (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.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Chlorothiazide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Chlorpromazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Chlorthalidone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Ciprofloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as ciprofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Clindamycin; Adapalene; 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.
Codeine; Phenylephrine; Promethazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Codeine; Promethazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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: (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.
Fluphenazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Gemifloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as gemifloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Glimepiride: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glipizide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glipizide; Metformin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glyburide: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Glyburide; Metformin: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Levofloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as levofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
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.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Metolazone: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Moxifloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as moxifloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Ofloxacin: (Major) Avoid the concomitant use of tretinoin with other drugs known to cause photosensitivity, such as ofloxacin. Concomitant use with other photosensitizing agents may increase the risk of a photosensitivity reaction.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Perphenazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Perphenazine; Amitriptyline: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Phenothiazines: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Pioglitazone; Glimepiride: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Porfimer: (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.
Prochlorperazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Promethazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Promethazine; Dextromethorphan: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Promethazine; Phenylephrine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Salicylic Acid: (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.
Sodium Thiosulfate; Salicylic Acid: (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.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Sulfonylureas: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as sulfonylureas, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Thiazide diuretics: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Thioridazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
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.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Trifarotene: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Trifluoperazine: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as phenothiazines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) A manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as thiazide diuretics, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Verteporfin: (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.
Tretinoin; benzoyl peroxide is administered topically to treat acne vulgaris.
-Tretinoin: Tretinoin is a metabolite of vitamin A that binds with high affinity to specific retinoic acid receptors (RAR) located in both the cytosol and nucleus. This binding activates 3 retinoic acid nuclear receptors (RAR-alfa, RAR-beta, and RAR-gamma) which modify gene expression, subsequent protein synthesis, and epithelial cell growth and differentiation. The exact mechanism by which tretinoin treats acne is unknown; however, evidence suggests that topical application of tretinoin decreases the cohesiveness of follicular epithelial cells with decreased microcomedo formation. Tretinoin also stimulates mitotic activity and increases turnover of follicular epithelial cells causing extrusion of the comedones.
-Benzoyl Peroxide: The exact mechanism of action of benzoyl peroxide in the treatment of acne is unknown; however, the drug is an oxidizing agent with bacteriocidal and keratolytic effects. The antibacterial effects of benzoyl peroxide are due to the release of free-radical oxygen species capable of oxidizing bacterial proteins. The drug also has a desquamative effect which may contribute to its efficacy.
Tretinoin; benzoyl peroxide is administered topically.
-Tretinoin: Following absorption, tretinoin is converted to 13-cis retinoic acid, 4-keto 13-cis retinoic acid, all-trans 4-keto retinoic acid, and 9-cis retinoic acid.
-Benzoyl peroxide: After absorption, benzoyl peroxide is converted to benzoic acid and excreted in the urine.
-Route-Specific Pharmacokinetics
Topical Route
-Tretinoin: Plasma concentrations of tretinoin and its major metabolites were assessed in an open-label study involving 35 patients (ages 9 years and older) who applied a mean daily dose of 1.9 grams of tretinoin; benzoyl peroxide to the face, shoulders, upper back, and upper chest once daily for 14 days. Steady-state pharmacokinetics were evaluated on Day 14. The mean maximum plasma concentrations (Cmax) and systemic exposures (AUC) of tretinoin were 0.15 +/- 0.17 ng/mL and 0.63 +/- 0.95 ng x hour/mL for adults (18 years and older), 0.19 +/- 0.18 ng/mL and 1.56 +/- 1.97 ng x hour/mL for adolescents (12 to 17 years), and 0.18 +/- 0.22 ng/mL and 2.06 +/- 3.96 ng x hour/mL for children (9 to 11 years), respectively. The mean Cmax for the 2 major metabolite (4-keto 13-cis RA and 13-cis RA) were 0.27 +/- 0.29 ng/mL and 0.21 +/- 0.19 ng/mL for adults, 0.32 +/- 0.28 ng/mL and 0.28 +/- 0.35 ng/mL for adolescents, and 0.34 +/- 0.36 ng/mL and 0.13 +/- 0.09 ng/mL for children, respectively. The mean AUC for 4-keto 13-cis RA and 13-cis RA were 2.88 +/- 3.61 ng x hour/mL and 1.99 +/- 2.9 ng x hour/mL for adults, 2.39 +/- 3.05 ng x hour/mL and 1.79 +/- 2.79 ng x hour/mL for adolescents, and 2.89 +/- 3.17 ng x hour/mL and 0.96 +/- 1.36 ng x hour/mL for children, respectively. No detectable concentrations of the metabolites all-trans 4-keto RA or 9-cis RA were observed.
-Benzoyl peroxide: The systemic exposure of benzoyl peroxide following application of tretinoin; benzoyl peroxide has not been assessed.