Hydroquinone is a topical depigmenting agent. It is structurally related to monobenzone, a potent depigmenting agent. Unlike monobenzone, depigmentation caused by hydroquinone is reversible. Hydroquinone is used for temporary bleaching of hyperpigmented skin conditions such as chloasma (melasma), freckles, and lentigines. Sunscreens must be used concomitantly with topical hydroquinone; several commercial preparations do contain a sunscreen agent. Hydroquinone is also used as an antioxidant for ether and in photographic development. Hydroquinone has been available since before 1938.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: A proper skin care and sun avoidance program including protective clothing should accompany the use of hydroquinone. The concurrent use of daily sunscreen is recommended both during and after discontinuation of treatment to prevent rehyperpigmentation. Some products (e.g., Eldopaque Forte cream and Solaquin Forte cream or gel) contain sunscreen agents which provide adequate sun protection during therapy. Products (e.g., Eldoquin Forte cream) that do not contain a sunscreen agent should be reserved for night-time use.
Route-Specific Administration
Topical Administration
Cream/Ointment/Lotion Formulations:
-Wash hands before and after application.
-Apply a thin layer of the cream, lotion or solution topically with the fingers. Refer to the product labeling to determine if the medication should be rubbed in; some formulations should not be rubbed into the skin.
-Do not apply the cream to the eye area; avoid contact with the mouth, eyes, and other mucous membranes. If contact with the eye(s) occur, the eye(s) should be washed with large amounts of water; contact prescriber if ocular irritation persists. Do not use on irritated, denuded, or damaged skin.
-Non-medicated cosmetics, sunscreens, and moisturizing lotions may be worn over the hydroquinone preparation. However, wait several minutes after application of hydroquinone before applying them.
The most common adverse reactions to topical hydroquinone therapy include skin irritation (burning, erythema, stinging), sensitization and contact dermatitis. Application of high concentrations or prolonged use can produce skin hyperpigmentation, especially on areas exposed to sunlight. Exogenous ochronosis (blue-black skin hyperpigmentation or skin discoloration) has been reported and is considered to be an adverse reaction to hydroquinone rather than an idiosyncratic reaction. Ochronosis may develop after 6 months of use and may be irreversible once established. Application to the paranasal and infraorbital areas increases the risk of skin irritation; xerosis and fissuring has occurred in these areas. If applied to the eye, corneal staining and corneal opacification may occur. If applied to the lips, a bitter taste and anesthetic effect may occur. Reversible brown nail discoloration of the hand may occur when applying hydroquinone. Systemic adverse reactions to topical hydroquinone have not been reported.
Some hydroquinone products contain parabens and/or sodium metabisulfite. Do not use hydroquinone in any patient that has a prior history of hydroquinone hypersensitivity, paraben hypersensitivity, sulfite hypersensitivity, or hypersensitivity to any of the ingredients contained in a product. Avoid ocular exposure as well as contact with the mouth and other mucous membranes. Do not use on skin which is irritated, denuded, or damaged or has a skin abrasion or sunburn. If hypersensitivity or contact dermatitis occur during hydroquinone therapy, immediately discontinue the drug and contact a physician. High concentrations or prolonged use of hydroquinone can produce skin hyperpigmentation, especially on areas exposed to sunlight. If sunlight (UV) exposure can not be avoided, use a product containing a sunscreen agent.
Safe and effective use of hydroquinone during pregnancy has not been established. Animal reproduction studies have not been conducted with topical hydroquinone. It is also not known whether it can cause fetal harm when used topically on a pregnant woman or affect reproductive capacity. The degree of systemic absorption, if any, is not known. Use during pregnancy only when clearly needed.
According to the manufacturer, it is not known whether topical hydroquinone is absorbed or excreted in human milk and caution is advised when it is used in breast-feeding mothers. The molecular weight is low enough for passage into breast-milk, but systemic absorption of the drug has not been studied. However, because it is a strong base, if it is absorbed, most of the compound would be in the ionized state and thus not available for excretion into 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 ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Safe and effective use of hydroquinone in neonates, infants, and children under 12 years has not been established.
For the treatment of lentigines (freckles) and/or other minor hyperpigmented skin conditions:
Topical dosage (OTC and Rx-only products):
Adults, Adolescents, and Children >= 12 years: Apply 2-4% topical preparation to the affected area twice daily. If no lightening effect is noted after 2 months of treatment, discontinue therapy.
Children < 12 years: Safety and efficacy have not been established.
For the gradual treatment of ultraviolet-induced dyschromia (photoaging) and discoloration resulting from pregnancy (chloasma or melasma), hormone replacement therapy, skin trauma, or the use of oral contraceptives:
Topical dosage (Rx-only products):
Adults, Adolescents, and Children >= 12 years: Apply 4% topical preparation to the affected area twice daily, morning and before bedtime, or as directed by a physician. If no lightening effect is noted after 2 months of treatment, discontinue therapy.
Children < 12 years: Safety and efficacy have not been established.
Maximum Dosage Limits:
-Adults
2 applications/day topically.
-Elderly
2 applications/day topically.
-Adolescents
2 applications/day topically.
-Children
>= 12 years: 2 applications/day topically.
< 12 years: 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: (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.
Benzoyl Peroxide: (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.
Benzoyl Peroxide; Clindamycin: (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.
Benzoyl Peroxide; Erythromycin: (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.
Benzoyl Peroxide; Sulfur: (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.
Clindamycin; Adapalene; Benzoyl Peroxide: (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.
Estradiol: (Moderate) Application of sunscreen 10 minutes prior to the application of topical estradiol increases the exposure to estradiol by approximately 35 percent. Application of sunscreen 25 minutes after the application of topical estradiol increases the exposure to estradiol by approximately 15 percent. Patients should be advised to separate the application of topical estradiol and sunscreens as long as possible in order to avoid increased estradiol absorption.
Estradiol; Levonorgestrel: (Moderate) Application of sunscreen 10 minutes prior to the application of topical estradiol increases the exposure to estradiol by approximately 35 percent. Application of sunscreen 25 minutes after the application of topical estradiol increases the exposure to estradiol by approximately 15 percent. Patients should be advised to separate the application of topical estradiol and sunscreens as long as possible in order to avoid increased estradiol absorption.
Estradiol; Norethindrone: (Moderate) Application of sunscreen 10 minutes prior to the application of topical estradiol increases the exposure to estradiol by approximately 35 percent. Application of sunscreen 25 minutes after the application of topical estradiol increases the exposure to estradiol by approximately 15 percent. Patients should be advised to separate the application of topical estradiol and sunscreens as long as possible in order to avoid increased estradiol absorption.
Oxybutynin: (Moderate) The effect on the pharmacokinetics of oxybutynin topical gel when sunscreens were applied 30 minutes before or after oxybutynin gel was evaluated in a single-dose randomized crossover study (n=16). The study revealed no difference in the absorption of oxybutynin gel when applied in this manner. However, the effects of sunscreen on oxybutynin absorption when used within 30 minutes of gel application have not been studied. Therefore, the manufacturer recommends that patients use sunscreen either 30 minutes before or after gel application.
Tretinoin; Benzoyl Peroxide: (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.
Hydroquinone inhibits melanin formation by blocking the enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) in melanocytes. Other melanocyte metabolic processes are also inhibited. Exposure to sunlight or ultraviolet light will cause repigmentation of bleached areas.
Pharmacokinetics:
Hydroquinone is applied topically to the skin.
-Route-Specific Pharmacokinetics
Topical Route
It is not known whether percutaneous absorption of hydroquinone occurs. Absorption of a topically applied drug may be affected by the conditions of the epidermis including overall pH, disease state, and genetically driven factors such as oiliness or dryness of the skin. The rate of absorption can affect the efficacy and tolerability of hydroquinone.
The sustained release formulation of hydroquinone (EpiQuin Micro) is a multi-phasic formulation containing 4 distinct phases including an oil phase, a water phase, and 2 microparticulate phases resulting from the incorporation of two different Microsponge delivery systems. The Microsponge delivery system extends the release of hydroquinone. The multi-phasic formulation allows for both immediate and gradual release of the hydroquinone.