Rx Only

FOR EXTERNAL USE ONLY

I. DESCRIPTION

Hydroquinone is 1,4-benzenediol. 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. Chemically, hydroquinone is designated as p-dihydroxybenzene; the empirical formula is C ₆ H ₆ O ₂ ; molecular weight 110.1. The structural formula is:

CONTENTS

ACTIVE INGREDIENT

Hydroquinone USP 4%.

OTHER INGREDIENTS

Purified Water, Phenyl Trimethicone, Glycerin 99% USP, Glyceryl Stearate (and) PEG-100 Stearate, Alcohol, Cetyl Alcohol NF, Linoleic Acid, Cyclopentasiloxane (and) Polysilicone-11, Polyacrylamide (and) C 13-14 Isoparaffin (and) Laureth-7, Cetearyl Alcohol (and) Ceteareth-20, Hydrogenated Lecithin, Tocopheryl Acetate, Triethanolamine 99% NF, Phenoxyethanol, Soybean Oil USP, Carnauba Wax, Ceteareth-20, Magnesium 1-Ascorbyl Phosphate, Benzyl Alcohol NF, Tocopherol, Dimethiconol, Retinol, Sodium Metabisulfite, Sodium Citrate USP, Disodium EDTA, Butylated Hydroxytoluene, Carbomer NF, Fragrance.

II. CLINICAL PHARMACOLOGY

Topical application of hydroquinone produces a reversible depigmentation of the skin by inhibition of the enzymatic oxidation of tyrosine to 3-(3,4-dihydroxyphenyl) alanine (dopa) ¹ and suppression of other melanocyte metabolic processes. ²

III. INDICATIONS AND USAGE

ALUSTRA is indicated for the gradual treatment of ultraviolet induced dyschromia and discoloration resulting from the use of oral contraceptives, pregnancy, hormone replacement therapy, or skin trauma.

IV. DOSAGE AND ADMINISTRATION

ALUSTRA should be applied to the affected areas twice daily, morning and before bedtime, or as directed by a physician. During and after the use of ALUSTRA sun exposure should be limited, and a sunscreen agent or sun-protective clothing should be used to cover the treated areas, to prevent repigmentation. There is no recommended dosage for pediatric patients under 12 years of age except under the advice and supervision of a physician.

V. CONTRAINDICATIONS

ALUSTRA is contraindicated in any patient that has a prior history of hypersensitivity or allergic reaction to hydroquinone or any of the other ingredients. The safety of topical hydroqinone use during pregnancy or on children (12 years and under) has not been established.

VI. WARNINGS

1. CAUTION: Hydroquinone is a depigmenting agent which may produce unwanted cosmetic effects if not used as directed. The physician should be familiar with the contents of this insert before prescribing or dispensing this medication.
2. Test for skin sensitivity before using ALUSTRA by applying a small amount to an unbroken patch of skin and check within 24 hours. Minor redness is not a contraindication, but where there is itching, vesicle formation, or excessive inflammatory response further treatment is not advised. Close patient supervision is recommended. Contact with the eyes should be avoided. If no lightening effect is noted after two months of treatment, use of ALUSTRA should be discontinued.
3. Sunscreen use is an essential aspect of hydroquinone therapy, because even minimal sunlight sustains melanocytic activity. During treatment and maintenance therapy, sun exposure should be avoided on treated skin by application of a broad spectrum sunscreen (SPF 15 or greater) or by use of protective clothing to prevent repigmentation. Although ALUSTRA has an antioxidant system in its vehicle, there are no sunblocking or sunscreening agents in ALUSTRA.
4. Keep this and all medications out of the reach of children. In case of accidental ingestion, contact a physician or a poison control center immediately.
5. WARNING: Contains sodium metabisulfite, a sulfite which may cause serious allergic reactions (e.g., hives, itching, wheezing, anaphylaxis, severe asthma attack) in certain susceptible persons.
6. On rare occasions, a gradual blue-black darkening of the skin may occur. In which case, use of ALUSTRA should be discontinued and a physician contacted immediately.

VII. PRECAUTIONS

SEE WARNINGS

A. Pregnancy Category C:   Animal reproduction studies have not been conducted with topical hydroquinone. It is also not known whether hydroquinone can cause fetal harm when used topically on a pregnant woman or can affect reproductive capacity. It is not known to what degree, if any, topical hydroquinone is absorbed systemically. Topical hydroquinone should be used in pregnant women only where clearly indicated.

B. Nursing mothers:   It is not known whether topical hydroquinone is absorbed or excreted in human milk. Caution is advised when hydroquinone is used by a nursing mother.

C. Pediatric usage:   Safety and effectiveness in pediatric patients below the age of 12 years have not been established.

VIII. ADVERSE REACTIONS

No systemic reactions have been reported. Occasional cutaneous hypersensitivity (localized contact dermatitis) may occur, in which case the medication should be discontinued and the physician notified immediately.

IX. OVERDOSAGE

There have been no systemic reactions reported from the use of topical hydroquinone. However, treatment should be limited to relatively small areas of the body at one time, since some patients experience a transient skin reddening and a mild burning sensation which does not preclude treatment.

X. HOW SUPPLIED

ALUSTRA is available as follows:

SIZE                              NDC NUMBER
1 ounce jar (28.4 g)        99207-251-10

REFERENCES

1. Denton, C., A.B. Lerner, and T.B. Fitzpatrick. "Inhibition of Melanin Formation by Chemical Agents." Journal of Investigative Dermatology . 1952; 18:119-135.
2. Jimbow, K., H. Obata, M. Pathak, and T.B. Fitzpatrick. "Mechanism of Depigmentation by Hydroquinone." Journal of Investigative Dermatology . 1974; 62:436-449.

Store at 15°-25°C (59°-77°F).

Covered by US Patent 5,932,612.

Manufactured for: MEDICIS, The Dermatology Company®, Scottsdale, AZ 85258 by: Contract Pharmaceuticals Limited, Mississauga, Ontario L5N 6L6 CANADA

Prescribing information as of April 2001.

25110-08A