VA Class:DE900

ATC Class:D11AX11

AHFS Class:

• Depigmenting Agents 84:50.04

Generic Name(s):

• Hydroquinone

Hydroquinone, which is structurally related to monobenzone, is a depigmenting agent.

Hyperpigmentation

Hydroquinone is applied topically to gradually reduce hyperpigmentation in conditions such as freckling (ephelides), inactive chloasma, generalized and senile lentigo, and other unwanted areas of melanin hyperpigmentation. The drug also has been used to reduce hyperpigmentation caused by photosensitization associated with inflammation or with the use of certain perfumes. Depigmentation produced by hydroquinone varies among patients in completeness, time of onset, and duration. Although hydroquinone rarely completely reduces hyperpigmentation and some patients exhibit no response to the drug, most clinicians consider hydroquinone to be useful in some patients with hyperpigmentation in which a large excess of melanin is not being produced. The results of one study indicate that a topical hydrophilic ointment containing 5% hydroquinone, 0.1% dexamethasone, and 0.1% tretinoin is more effective and depigments chloasma more rapidly than does topical hydroquinone alone; however, further studies are needed to fully assess the safety and efficacy of this combination.

Other Uses

Hydroquinone, in concentrations of less than 1%, is used as an antioxidant in topical preparations.

Administration

Preparations containing 2-4% hydroquinone are applied topically. Hydroquinone should not be administered orally.

Dosage

To depigment hyperpigmented skin, a thin layer of hydroquinone cream or solution should be applied uniformly and rubbed into the pigmented area twice daily, in the morning and evening. Application of the drug should be limited to an area equal to that of the face and neck or hands and arms. Exposure to sunlight should be minimized during treatment (See Cautions: Precautions and Contraindications); the opaque base in some hydroquinone preparations (Eldopaque^®, Eldopaque Forte^®) may provide sufficient protection from sunlight. If no depigmentation is evident after 2 months of hydroquinone treatment, the drug should be discontinued. When the desired degree of depigmentation is obtained, hydroquinone should be applied only as often as needed to maintain depigmentation.

Adverse Effects

Mild skin irritation and sensitization, including burning, stinging, and allergic dermatitis, have occurred following topical application of hydroquinone and reportedly occur more frequently with 4% than with 2% concentrations of the drug. Topical corticosteroids may be used to reduce irritation and sensitization. Dryness and fissuring of paranasal and infraorbital areas has also been reported. Chronic use (up to 8 years) of 5% hydroquinone creams has been reported to produce ochronosis and colloid milium.

Precautions and Contraindications

Hydroquinone is a skin bleaching agent that may produce unwanted cosmetic effects if not used as directed. The physician should be thoroughly familiar with the use, adverse effects, and precautions and contraindications of hydroquinone before prescribing or dispensing the drug. Hydroquinone should not be used for the prevention of sunburn.

Hydroquinone should not be applied near the eyes; to cut, abraded, or sunburned skin; after shaving or using a depilatory agent; or over miliaria rubra (prickly heat). One manufacturer recommends that small amounts of the commercially available 2 or 4% hydroquinone preparations be applied to an area of unbroken skin about 25 mm in diameter prior to depigmentation therapy with the drug to assess the risk of irritation or allergic reactions. The test site is examined after 24 hours; minor redness is not a contraindication, but if itching, vesicle formation, or excessive inflammation occurs, treatment with the drug is not advised. Alternatively, some clinicians recommend use of an extemporaneously prepared 1% hydroquinone in petrolatum ointment to test for allergy. If rash or irritation develops during hydroquinone therapy, treatment should be discontinued, the drug washed off, and a physician consulted.

Since minimal exposure to sunlight may reverse the bleaching effect of hydroquinone, unnecessary exposure to sunlight should be avoided during and after therapy. If hydroquinone preparations which do not contain sunscreen agents are used during the daytime, sunscreen agents and/or protective clothing should be used to minimize exposure and prevent repigmentation of treated areas; alternatively, these preparations should be used only at night (and the usual preventive measures employed during the daytime), or daytime use of preparations containing sunscreen agents may be considered. After reduction of hyperpigmentation and during maintenance therapy, use of sunscreen agents and/or protective clothing should continue.

Some commercially available topical formulations of hydroquinone contain sulfites that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

Hydroquinone is contraindicated in patients with a history of sensitivity or allergic reaction to the drug or any ingredients in the commercially available preparations.

Pediatric Precautions

Safety and efficacy of hydroquinone in children younger than 12 years of age have not been established.

Pregnancy, Fertility, and Lactation

Pregnancy

Reproductive studies in animals have not been performed with topical hydroquinone. It is not known whether hydroquinone can cause fetal harm when used topically by pregnant women. Topical hydroquinone should be used during pregnancy only when clearly needed.

Fertility

The effect of hydroquinone on fertility is not known.

Lactation

Since it is not known if topical hydroquinone is absorbed or distributed into human milk, the drug should be used with caution in nursing women.

Acute Toxicity

Adults ingesting 300-500 mg of hydroquinone daily for 3-5 months have reported no toxic adverse effects. However, single oral doses of 5-12 g of hydroquinone have produced symptoms similar to those following phenol overdosage, including tremors, seizures, and, occasionally, severe hemolytic anemia.

Systemic overdosage of hydroquinone, like phenol, should be treated with measures intended to reduce absorption of the drug, including administration of activated charcoal and gastric lavage, and supportive therapy.

Pharmacology

Following topical application in animals, hydroquinone increases the excretion of melanin from melanocytes; the same action is thought to be responsible for the depigmenting effect of the drug in humans. Some pharmacologists believe that hydroquinone may also prevent melanin production. Unlike monobenzone, hydroquinone reportedly does not cause destruction of melanocytes or permanent depigmentation. Depigmentation may take 1-4 months to occur while existing melanin is lost with the normal sloughing of the stratum corneum and excretion of new melanin is increased by hydroquinone. Hyperpigmented skin appears to fade more rapidly and completely than does normal skin and exposure to sunlight reduces the depigmenting effect of the drug. Depigmentation usually persists for 2-6 months following discontinuance of hydroquinone treatment.

Pharmacokinetics

Information on the absorption, distribution, and elimination of hydroquinone is not available.

Chemistry and Stability

Chemistry

Hydroquinone is structurally related to monobenzone. Hydroquinone occurs as fine, white needles. The drug is freely soluble in water and in alcohol and has a pK_a of 9.96.

Stability

Commercially available hydroquinone preparations should be stored in light-resistant containers. Hydroquinone darkens upon exposure to light and air and is incompatible with alkalis, ferric salts, and oxidizing agents.