Hydroquinone

Class: Depigmenting Agents
ATC Class: D11AX11
VA Class: DE900
Chemical Name: 1,4 p-dihydroxybenzene
Molecular Formula: C6H6O2
CAS Number: 123-31-9
Brands: Aclaro PD, Alphaquin HP, Claripel, Eldopaque Forte, Eldoquin Forte, EpiQuin Micro, Esoterica, Esoterica Regular, Glyquin XM, Lustra, Lustra-Ultra, Melpaque HP, Melquin, Nuquin HP, Solaquin, Tri-Luma

Introduction

Depigmenting agent; structurally related to monobenzone.a h s

Uses for Hydroquinone

Hyperpigmentation

Used to reduce hyperpigmentation in conditions such as freckling (ephelides), inactive chloasma, melasma, generalized and senile lentigo, and other unwanted areas of melanin hyperpigmentation.a b m

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Used for gradual treatment of ultraviolet-induced dyschromia and skin discoloration resulting from the use of oral contraceptives, pregnancy, hormone replacement therapy, or skin trauma.p s

Most clinicians consider hydroquinone to be useful in some patients with hyperpigmentation in which a large excess of melanin is not being produced.a

Has been used to reduce hyperpigmentation caused by photosensitization associated with inflammation or with the use of certain perfumes.a

Used in combination with fluocinolone and tretinoin for short-term and intermittent long-term treatment of moderate to severe melasma.q

Hydroquinone Dosage and Administration

General

  • Depigmentation varies among patients in completeness, time of onset, and duration; rarely completely reduces hyperpigmentation and some patients exhibit no response to the drug.a

  • May require 1–4 months for depigmentation effects to occur.a Following discontinuance of hydroquinone, depigmentation effects usually persist for 2–6 months.a

  • Avoid unnecessary exposure to sunlight during and after therapy.a b h p s

  • Prior to initiating therapy, assess the risk of irritation or allergic reactions by applying a small amount of hydroquinone preparation to an area of unbroken skin.a b h m p s After 24 hours, examine test site; discontinue treatment if itching, vesicle formation, or excessive inflammation occurs; however, minor redness is not a contraindication for further treatment.a b h p s

Administration

Topical Administration

Apply topically to the skin as a cream, gel, emulsion, or solution.a b m p q s (See Sensitivity Reactions under Cautions.)

Limit application to an area equal to that of the face and neck or hands and arms.a s

For dermatologic use only; avoid contact with eyes.a b q s If such contact occurs, flush the affected eye(s) with copious amounts of water and contact a clinician.b

Not for oral administration.a

Apply hydroquinone cream, gel, emulsion, or solution (with or without sunscreens) uniformly to pigmented area and rub into skin.a b p s Do not rub cream containing opaque sunblocking agents (e.g., talc) into the skin.b h

If hydroquinone preparations without sunscreen agents are applied during the daytime, use sunscreen agents and/or protective clothing to minimize exposure and prevent repigmentation of treated areas; alternatively, apply these preparations only at night.a b h p q

Gently wash face and neck with mild soap, rinse, and pat dry before applying fixed-combination hydroquinone, fluocinolone, and tretinoin cream to affected area(s).q

Apply a small amount of fixed-combination hydroquinone, fluocinolone, and tretinoin cream to affected area(s), including about ½ inch of normal skin surrounding each lesion.q Rub lightly and uniformly into the skin.q Do not use occlusive dressing.q

Dosage

When the desired degree of depigmentation is obtained, apply only as often as needed to maintain depigmentation.a

Pediatric Patients

Hyperpigmentation
Topical

Adolescents >12 years of age: Apply hydroquinone cream, emulsion, gel, or solution (with or without sunscreens) uniformly to pigmented area(s) and rub in well twice daily, in the morning and evening.a b p s

If improvement does not occur after 2 months of treatment, discontinue the drug.b p s

Adults

Hyperpigmentation
Topical

Hydroquinone cream, emulsion, gel, or solution (with or without sunscreens): Apply uniformly to pigmented area(s) and rub in well twice daily, in the morning and evening or as directed by a clinician.a b h p s

Hydroquinone cream with opaque sunblock: Apply uniformly to the pigmented area(s) twice daily, in the morning and evening; do not rub into affected area(s).b h

If improvement does not occur after 2 months of treatment, discontinue the drug.b p

Melasma
Topical

Fixed-combination hydroquinone, fluocinolone, and tretinoin cream: Apply a thin layer uniformly to the affected area(s) once daily, in the evening, at least 30 minutes before bedtime.q Continue daily for as long as the melasma lesions persist.q Discontinue treatment when melasma resolves.q

If melasma reoccurs, repeat treatment until condition resolves.q

Prescribing Limits

Pediatric Patients

Hyperpigmentation
Topical

Adolescents >12 years of age: Maximum 2 months of therapy if no improvement is seen.b

Adults

Hyperpigmentation
Topical

Maximum 2 months of therapy if no improvement is seen.b p s

Melasma
Topical

Fixed-combination hydroquinone, fluocinolone, and tretinoin cream has been safely administered for cumulative ≥180 days.q

Special Populations

Geriatric Patients

Clinical studies of 4% hydroquinone cream did not include sufficient number of patients ≥65 years of age to determine whether they respond differently from younger patients. In general, dosage selection for geriatric patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.

Cautions for Hydroquinone

Contraindications

  • History of sensitivity or allergic reaction to hydroquinone or any ingredient in the formulation.a b p q s

Warnings/Precautions

Warnings

Cosmetic Effects

May produce undesired cosmetic effects (e.g., excessive skin bleaching)q if not used as directed.a b p s Clinician should be familiar with the use, adverse effects, precautions, and contraindications before prescribing or dispensing the drug.a p s

Exposure to Sunlight or Ultraviolet Light

Exposure to sunlight or ultraviolet light may cause repigmentation of bleached areas.a b h p q Avoid unnecessary exposure to sunlight during and after therapy.a b h p s

Sunscreen agents and/or protective clothing recommended if preparations which do not contain sunscreen are applied during the daytime.a b h p q s Preparations containing sunscreen may provide sufficient protection from sunlight.a b h

After reduction of hyperpigmentation and during maintenance therapy, continue the use of sunscreen agents and/or protective clothing.a b h

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.y z aa bb cc dd ee ff

Other Sensitivity Reactions

Contact dermatitis reported.b h p q s If contact dermatitis occurs, discontinue immediately and contact a clinician.p q s

Major Toxicities

Rarely, ochronosis (gradual blue-black darkening of the skin) and colloid milium reported with chronic use (up to 8 years) of 5% hydroquinone cream. a o p q If affected skin changes to a blue-black color, discontinue immediately and contact a clinician.p q

General Precautions

Topical Use

For external use only.b Notfor topical application in the eyes, ears, or mouth;a b p to cut, abraded,m or sunburned skin; after shaving or using a depilatory agent; or over miliaria rubra (prickly heat).a

Dermatologic Effects

Possible local skin irritation (e.g., burning, stinging, mild erythema).a h Dryness and fissuring of paranasal and infraorbital areas reported.a b

Use of Fixed Combinations

When hydroquinone is used in fixed combination with topical sunscreens (e.g., dioxybenzone, oxybenzone, and padimate), fluocinolone, or retinoids (e.g., tretinoin), consider the cautions, precautions, and contraindications associated with these agents.b h p q

Specific Populations

Pregnancy

Category C.b

Lactation

Not known if topical hydroquinone is distributed into milk.a b Caution advised if topical hydroquinone is used.a b

Pediatric Use

Safety and efficacy of hydroquinone preparations not established in children <12 years of age.a b

Safety and efficacy of the fixed-combination hydroquinone, fluocinolone, and tretinoin cream not established in pediatric patients of any age.q

Common Adverse Effects

Mild skin irritation and sensitization (e.g., burning, erythema, stinging).a h

Hydroquinone Pharmacokinetics

Absorption

Duration

Depigmentation effects usually persist for 2–6 months following discontinuance of therapy.a

Stability

Storage

Topical

Manufacturer states that a slight darkening of hydroquinone preparation(s) is normal and will not affect potency.b

Cream, Gel, Emulsion, or Solution

Tight, light-resistant containersa b at 25°C (may be exposed to 15–30°C).h p s

Combination (Hydroquinone 4%, Fluocinolone acetonide 0.01%, and Tretinoin 0.05%) Cream

Tight, light-resistant containers at 20–25°C.q Do not freeze.q

Actions

  • May produce a reversible skin depigmentation by inhibiting the enzymatic oxidation of tyrosine to 3, 4-dihydroxyphenylalanine (DOPA) and suppressing other melanocyte metabolic processes.b p q s

  • Increases the excretion of new melanin while existing melanin is lost during the normal sloughing of the stratum corneum.a

  • May prevent melanin production; however, does not cause destruction of melanocytes or permanent depigmentation.a

Advice to Patients

  • Importance of advising patients that topical hydroquinone is a bleaching agent and should not be used for the prevention of sunburn.a

  • Importance of avoiding contact with eyes.a b s If ocular contact occurs, rinse eye(s) promptly and thoroughly with water.b

  • Importance of advising patients that a bitter taste and an antiseptic effect may occur if hydroquinone is applied to lips.b

  • Importance of keeping hydroquinone preparations out of the reach of children.b h p

  • Importance of using sunscreen products (SPF ≥15)p and wearing protective clothing over treated areas.a b h q s Avoid exposure to sunlight, sunlamp, or ultraviolet light during and after treatment.p q

  • Importance of discontinuing drug and informing clinician if an allergic or hypersensitivity (e.g., contact dermatitis) reaction occurs.b h m q

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.b q s

  • Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.m q

  • Importance of informing patients of other important precautionary information.q (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Hydroquinone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Topical

Cream

2%

Esoterica Regular (with parabens, propylene glycol, and sodium bisulfite)

Medicis

4%

Aclaro PD (with benzyl alcohol and propylene glycol)

Johnson & Johnson

Eldopaque Forte (with propylene glycol and sodium metabisulfite in an opaque base)

Valeant

Eldoquin Forte (with propylene glycol, propylparaben, and sodium metabisulfite)

Valeant

EpiQuin Micro (with benzyl alcohol, methylparaben, retinol 0.15%, and sodium metabisulfite in a polymeric system)

SkinMedica

Hydroquinone Cream (with parabens, propylene glycol, and sodium metabisulfite)

Ethex

Lustra (with benzyl alcohol and sodium metabisulfite)

Taro

Lustra-Ultra (with parabens, propylene glycol, retinol 0.3%, and sodium metabisulfite)

Taro

Melpaque HP (with parabens, propylene glycol, and sodium metabisulfite in an opaque talc base)

Stratus

Melquin HP (with propylene glycol and sodium metabisulfite)

Stratus

Solution

3%

Melquin-3 (with SD alcohol 45%, isopropyl alcohol 4%, and propylene glycol)

Stratus

Hydroquinone Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

2% with Benzophenone-3 2.5% and Octyl Dimethyl 3.3%

Esoterica Daytime with Moisturizer (with parabens, propylene glycol, and sodium bisulfite)

Medicis

Esoterica Daytime Sunscreen (with parabens, propylene glycol, and sodium bisulfite)

Medicis

Esoterica Nighttime with Moisturizer (with parabens, propylene glycol, and sodium bisulfite)

Medicis

4% with Avobenzone 3% and Octinoxate 7.5%

Claripel Cream with Sunscreens (with parabens, propylene glycol, and sodium metabisulfite)

Stiefel

4% with Avobenzone 3%, Oxybenzone 4%, and Octocrylene 8%

Glyquin XM (with methylparaben and propylene glycol)

Valeant

4% with Benzophenone-3 5% and Octyl Methoxycinnamate 7.5%

Alphaquin HP (with propylene glycol and sodium metabisulfite)

Stratus

4% with Dioxybenzone 3%, Oxybenzone 2%, and Padimate O 8%

Hydroquinone Cream with Sunscreens (with parabens, propylene glycol, and sodium metabisulfite)

Ethex

Hydroquinone Cream with Sunscreens (with propylene glycol and sodium metabisulfite)

Perrigo

Nuquin HP (with propylene glycol and sodium metabisulfite)

Stratus

Solaquin Forte (with propylene glycol and sodium metabisulfite)

Valeant

4% with Fluocinolone Acetonide 0.01% and Tretinoin 0.05%

Tri-Luma (with sodium metabisulfite)

Galderma

Gel

4% with Dioxybenzone 3% and Padimate O 5%

Hydroquinone Forte Gel (with propylene glycol and sodium metabisulfite)

Perrigo

Nuquin HP (with alcohol, propylene glycol, and sodium metabisulfite)

Stratus

Solaquin Forte (with propylene glycol and sodium metabisulfite)

Valeant

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS Drug Information 2007. McEvoy GK, ed. Hydroquinone. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 3551-2.

b. Stratus Pharmaceuticals. Alphaquin HP (hydroquinone 4%) cream product information. Miami, FL. 2007

h. ICN Pharmaceuticals. Eldoquin Forte (hydroquinone 4%) cream, Eldopaque Forte(hydroquinone 4% with sun block) cream, Solaquin Forte (hydroquinone 4% with sunscreens, SPF 17) cream and Solaquin Forte (hydroquinone 4% with sunscreens) gel product information. Costa Mesa, CA;1998 Sept.

m. Medicis. Esoterica (hydroquinone USP, 2%) cream product information. Phoenix, AZ.

o. Food and Drug Administration. Skin Bleaching Drug Products For Over-the-Counter Human Use. Proposed Rule. [21 CFR Part 310] Fed Regist. 2006. 71:167: 51146-54.

p. SkinMedica. EpiQuin Micro (hydroquinone 4% and retinol) skin bleaching moisturizing topical cream prescribing information. 2003 Sept.

q. Galderma Laboratories. TRI-LUMA(fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) cream prescribing information. Fort Worth, TX; 2003 Dec.

s. JSJ Pharmaceuticals. Aclaro PD (hydroquinone 4%) bioadhesive emulsion product information. Charleston, SC; 2007 Jan.

t. JSJ Pharmaceuticals. Charleston, SC: Personal communication.

y. Food and Drug Administration. Sulfites in foods and drugs. FDA Drug Bull. 1983; 13:12. [PubMed 6604672]

z. Sogn D. The ubiquitous sulfites. JAMA. 1984; 251:2986 7. Editorial. [IDIS 185969] [PubMed 6716628]

aa. Koepke JW, Christopher KL, Chai H et al. Dose dependent bronchospasm from sulfites in isoetharine. JAMA. 1984; 251:2982 3. [IDIS 185966] [PubMed 6716626]

bb. Twarog FJ, Leung DYM. Anaphylaxis to a component of isoetharine (sodium bisulfite). JAMA. 1982; 248:2030 1. [IDIS 158261] [PubMed 7120631]

cc. Baker GJ, Collett P, Allen DH. Bronchospasm induced by metabisulphite containing foods and drugs. Med J Aust. 1981; 2:614 7. [IDIS 146240] [PubMed 7334982]

dd. Koepke JW, Selner JC, Dunhill AL. Presence of sulfur dioxide in commonly used bronchodilator solutions. J Allergy Clin Immunol. 1983; 72:504 8. [IDIS 178793] [PubMed 6630799]

ee. Food and Drug Administration. Sulfiting agents; labeling in drugs for human use: warning statement. [Docket No. 84N 0113] Fed Regist. 1985; 50:47558 63.

ff. Food and Drug Administration Center for Food Safety and Applied Nutrition. The reexamination of the GRAS status of sulfiting agents, January 1985. (Doc. No. 223-83-2020.) Bethesda, MD: FASEB Life Sciences Research Office.

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