HYDROQUINONE
 0.0 OVERVIEW
 A. Hydroquinone is a depigmenting agent.
 B. DOSING INFORMATION: The usual dose of topical hydroquinone 2% to 4% is one
application twice daily.
 C. PHARMACOKINETICS: The onset and duration of depigmentation produced by
hydroquinone varies among individuals.
 D. CAUTIONS: The application of hydroquinone should be limited to relatively small areas of the
body at any one time. This agent should not be used in the eyes or on open wounds, and if skin
irritation develops, hydroquinone should be discontinued immediately.
 E. CLINICAL APPLICATIONS: Hydroquinone is used for reversible depigmentation of
hyperpigmented skin due to conditions such as freckles, senile lentigines, melasma, and
chloasma.
 1.0 DOSING INFORMATION
 1.1 DOSAGE FORMS
 A. Information on specific products and dosage forms can be obtained by referring to
the Product Index.
 1.3 ADULT DOSAGE
 1.3.1 NORMAL DOSE
 A. TOPICAL
 1. The usual dose of hydroquinone 4% topical preparations in the
treatment of HYPERPIGMENTATION is one application twice daily to
the affected area(s). If no response is noted after 2 months of therapy,
hydroquinone should be discontinued (Prod Info Solaquin Forte(R),
1994; Prod Info Eldopaque Forte(R), 1994; Prod Info Eldoquin
Forte(R), 1994).
 2.0 PHARMACOKINETICS
 2.3 ADME
 2.3.1 ABSORPTION
 A. TOPICAL, 35% (Bucks et al, 1988).
 3.0 CAUTIONS
 3.2 PRECAUTIONS
 A. Limit to relatively small areas of the body at any one time.
 B. Do not use in eyes or on open wounds.
 C. If irritation develops, discontinue immediately.
 3.3 ADVERSE REACTIONS
 3.3.6 KIDNEY/GENITOURINARY
 A. URINE DISCOLORATION
 See Drug Consult reference: "URINE DISCOLORATION - DRUG AND
DISEASE INDUCED"
 3.3.8 OCULAR
 A. OCULAR EFFECTS
 1. CONJUNCTIVAL CHANGES have been associated with
hydroquinone exposure (Reynolds, 1990).
 3.3.10 SKIN
 A. DERMATOLOGIC EFFECTS
 1. In a randomized, double-blind, comparative study of azelaic acid
20% and hydroquinone 2% cream for the treatment of melasma in 155
patients, side effects from both preparations consisted of transient
mild to moderate irritant reactions. Symptoms of BURNING, ITCHING
and/or STINGING occurred in 9 of 78 patients receiving hydroquinone
(Verallo-Rowell et al, 1989).
 2. Transient ERYTHEMA, mild burning, stinging, DRYNESS and
fissuring of paranasal and infraobital areas have been reported with
hydroquinone use (Reynolds, 1990; Fisher, 1983).
 B. VITILIGO
 1. Isolated cases of widespread contact LEUKODERMA and contact
vitiligo have been reported with topical hydroquinone use (Fisher,
1983; Boyle & Kennedy, 1985; Romaguera & Grimalt, 1985; George,
1989).
 2. Confetti-like DEPIGMENTATION occurred in a 63-year-old male
diabetic following the daily application to the beard area of a
hydroquinone-containing cream for a 3-month period (Ambi Extra for
Men(R)) (Markey et al, 1989). Gradual repigmentation of the affected
area began 4 months after discontinuation of the Ambi cream.
 C. DERMATITIS
 1. Localized CONTACT DERMATITIS has been reported with topical
hydroquinone use (Prod Info Solaquin Forte(R), 1994).
 2. Contact dermatitis developed in a 34-year-old female following the
use a cream containing hydroquinone (strength not reported) and
PABA (para-aminobenzoic acid) for treatment of chloasma. Patch test
revealed a positive reaction to hydroquinone 1% (Romaguera &
Grimalt, 1985).
 D. OCHRONOSIS
 1. SUMMARY: Ochronosis secondary to the application of
hydroquinone-containing creams has been reported by several
investigators. This paradoxical hyperpigmentation of the skin is
usually associated with long-term use of hydroquinone bleaching
creams. The hyperpigmentation usually fades following
discontinuation of the cream; however, in severe cases, it may be
irreversible (Anon, 1987; Brauer, 1985; Weiss et al, 1990).
 2. Ochronosis-like PIGMENTATION described as pitch-black
pigmentation and colloid millium formation was noted following the
use of 2% hydroquinone-containing creams in 2 black American
patients. These skin changes were accentuated in areas of sun
exposure (Hoshaw et al, 1985).
 3. Exogenous ochronosis occurred in a 36-year-old MexicanAmerican female following the application of hydroquinone 2% cream
for less than 6 months (Howard & Furner, 1990).
 4. SARCOID-LIKE OCHRONOSIS developed following treatment with
hydroquinone 4% cream for dark spots (possibly a form of melasma).
A discrete, nonpruritic papular eruption was noted on both cheeks of
the patient, which was successfully treated with tetracycline with
resolution of the lesions in 3 months (Fisher, 1988).
 E. NAIL DISCOLORATION
 1. FINGERNAIL STAINING due to hydroquinone-containing cream
was reported in 2 older females (Mann & Harman, 1983). Both
patients had applied hydroquinone 2%-containing cream twice daily
to the back of their hands for actinic lentigines. The staining was
described as a brown discoloration.
 F. HAIR CHANGES
 See Drug Consult reference: "DRUG-INDUCED HAIR CHANGES"
 3.3.12 OTHER
 A. OVERDOSE See POISINDEX(R) Management "HYDROQUINONEQUINONE"
 B. HYPERSENSITIVITY
 1. Occasional hypersensitivity reactions have occurred following
hydroquinone use, and skin sensitivity testing is recommended by
applying a small amount of hydroquinone on an unbroken patch of
skin for 24 hours (Prod Info Solaquin Forte(R), 1994; Fisher, 1983;
Ketel, 1984).
 3.4 TERATOGENICITY/EFFECTS IN PREGNANCY
 A. TERATOGENICITY
 1. U.S. Food and Drug Administration's Pregnancy Category C (Prod Info
Eldoquin Forte(R), 1997).
 See Drug Consult reference: "PREGNANCY RISK CATEGORIES"
 4.0 CLINICAL APPLICATIONS
 4.2 PATIENT INSTRUCTIONS
HYDROQUINONE (HYE-droe-kwin-one) (FOR THE SKIN):
- Lightens freckles and brown patches on the skin (liver
spots).
BRAND NAME(S): Eldopaque Forte(R), Eldoquin Forte(R),
Solaquin Forte(R), Melanex(R)
WHEN YOU SHOULD NOT TAKE THIS MEDICINE:
- Do not use this medicine if you have had an allergic
reaction to hydroquinone.
HOW TO TAKE AND STORE THIS MEDICINE
CREAM/LOTION/GEL/SOLUTION:
- Your doctor will tell you how much to use and how
often.
- Use only on the skin.
- Put a small amount of medicine on the skin spots.
- Keep the medicine away from your eyes and mouth.
- If you do get medicine in your eyes, rinse your eyes
with water and call your doctor.
- Wash your hands with soap and water after using this
medicine.
- Store the medicine at room temperature away from heat
and moisture. Do not freeze.
- Keep all medicine out of the reach of children.
IF YOU MISS A DOSE:
- Use the missed dose as soon as possible.
- If it is almost time for your next regular dose, wait
until then to use the medicine and skip the missed
dose.
- Do not put on two doses at the same time.
DRUGS AND FOODS TO AVOID:
Ask your doctor or pharmacist before taking any other
medicine, including over-the counter products.
WARNINGS:
- If you are pregnant or breastfeeding, talk to your
doctor before using this medicine.
- Make sure your doctor knows if you have other medical
problems.
- Protect your skin from the sun with clothing or
sunscreen while using this medicine.
SIDE EFFECTS
Call your doctor right away if you have any of these side
effects:
- Skin rash, redness, swelling, or intense itching
If you have problems with these less serious side effects,
talk with your doctor:
- Itching or mild stinging
IF YOU HAVE OTHER SIDE EFFECTS THAT YOU THINK ARE CAUSED BY
THIS MEDICINE, TELL YOUR DOCTOR
 4.3 PLACE IN THERAPY
 A. Hydroquinone can be used to lighten hyperpigmented areas of the skin associated
with chloasma, melasma, freckles, senile lentigines, and other forms of
hyperpigmentation caused by melanin.
 B. Theoretically, hydroquinone has the potential to be an effective agent for the
treatment of hypermelanosis. Additionally, several clinical studies comfirm its efficacy
as a bleaching agent. However, adverse effects (ie, unpredictable skin sensitization in
some patients, reversal of depigmentary effects from subsequent exposure to
ultraviolet light) and incomplete disappearance of pathologic hypermelanosis following
treatment may restrict its use.
 4.4 MECHANISM OF ACTION/PHARMACOLOGY
 A. MECHANISM OF ACTION
 1. Hydroquinone produces reversible depigmentation of the skin by
suppression of melanocyte metabolic processes, in particular the inhibition of
the enzymatic oxidation of tyrosine to DOPA (3,4-dihydroxyphenylalanine)
(Prod Info Solaquin Forte(R), 1994). Sun exposure reverses this effect, and will
cause repigmentation (Reynolds, 1990).
 B. REVIEW ARTICLES
 1. Efficacy of hydroquinone as a bleaching cream is discussed (Hart & Yi,
1993).
 4.5 THERAPEUTIC USES
 A. HYPERPIGMENTATION
FDA Labeled Indication
 1. OVERVIEW:
FDA APPROVAL: Adult, yes;
pediatric, yes (over 12 years)
EFFICACY: Adult, effective; pediatric,
effective
DOCUMENTATION: Adult, good; pediatric, good
 2. SUMMARY:
- Used to lighten hyperpigmented areas of
the skin
associated with CHLOASMA, MELASMA,
FRECKLES,
SENILE LENTIGINES, and other forms of
hyperpigmentation caused by melanin (Prod
Info
Solaquin Forte(R), 1994; Fisher, 1983)
 3. ADULT:
 a. Addition of kojic acid to hydroquinone and glycolic acid
combination may improve efficacy in the treatment of MELASMA.
Forty Chinese women received twice a day 2% hydroquinone and
10% glycolic acid combination gel in one half of the face, and
received 2% kojic acid, 2% hydroquinone, and 10% glycolic acid
combination gel on the other half of the face in a double-blind
randomized manner. After 12 weeks, patients with greater than 50%
improvement in melasma were found in 60% of the side with kojic
acid and 48% of the side without kojic acid. Both formula improved
melasma, but the difference between the 2 was not statistically
significant (p=0.9). Three patients developed redness and irritation
and withdrew from the study. All patients experienced redness,
stinging, and mild exfoliation on both sides of the face. The adverse
effects were settled by the third week. Kojic acid did not worsen side
effects and could be added to the treatment regimen if patients did
not respond to the hydroquinone and glycolic acid combination (Lim,
1999).
 4. PEDIATRIC:
 a. Resolution of hyperpigmentation secondary to a JELLYFISH STING
was described in a 17-year-old patient following treatment with topical
hydroquinone 1.8% twice daily for 40 days (Kokelj & Burnett, 1990).
 4.6 COMPARATIVE EFFICACY AND EVALUATION WITH OTHER SIMILAR THERAPEUTIC
AGENTS
 A. AZELAIC ACID
 1. MELASMA:
 a. Relatively large double-blind studies have reported that topical
azelaic acid 20% cream is superior to topical hydroquinone 2%
cream (Verallo-Rowell et al, 1989) and comparable in efficacy to
hydroquinone 4% cream (Fitton & Goa, 1991; Balina & Graupe, 1991)
in the treatment of melasma. The incidence of local adverse effects
with 20% azelaic acid cream and 2% to 4% hydroquinone were
comparable (Fitton & Goa, 1991).