PEDIATRIC USE SECTION.

Pediatric Use. Safety and effectiveness for pediatric patients below the age of 12 years have not been established.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. The following adverse reactions have been reported: dryness and fissuring of paranasal and intraorbital areas, erythema, and stinging. Occasional hypersensitivity (localized contact dermatitis) may develop. If this occurs, the medication should be discontinued and the physician notified immediately.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. Studies of hydroquinone in animals have demonstrated some evidence of carcinogenicity. The carcinogenic potential of hydroquinone in humans is unknown. Published studies have demonstrated that hydroquinone is mutagen and clastogen. Treatment with hydroquinone has resulted in positive findings for genetic toxicity in the Ames assay in bacterial strains sensitive to oxidizing mutagens, in in vitro studies in mammalian cells, and in the in vivo mouse micronucleus assay.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Topical application of hydroquinone produces reversible depigmentation of the skin by inhibition of the enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylalanine (dopa) (Denton, C. et al., 1952)1 and suppression of other melanocyte metabolic processes (Jimbow, K. et al., 1974)2. Exposure to sunlight or ultraviolet light will cause repigmentation of bleached areas (Parrish, J.A. et al., 1978)3.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Prior history of sensitivity or allergic reaction to hydroquinone or to any of the ingredients of the product. The safety of topical hydroquinone use during pregnancy or for children (12 years and under) has not been established.

DESCRIPTION SECTION.

DESCRIPTION. Each gram of Hydroquinone USP, 4% Skin Bleaching Cream contains 40 mg hydroquinone USP, in vanishing cream base of aqua (water), ascorbic acid, BHT, cetyl alcohol, disodium EDTA, glycerin, glycolic acid, methylparaben, propylparaben, saponins, sodium lauryl sulfate, sodium metabisulfite, stearyl alcohol and tocopheryl acetate. Chemically, hydroquinone is C6H6O2 and has molecular weight of 110.11. The chemical name is 1,4 dihydroxybenzene, and the structural formula of hydroquinone is:. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. Hydroquinone USP, 4% Skin Bleaching Cream should be applied to affected areas and rubbed in well twice daily, in the morning and before bedtime, or as directed by physician. If no improvement is seen after months of treatment, use of this product should be discontinued. There is no recommended dosage for pediatric patients under 12 years of age except under the advice and supervision of physician.

DRUG INTERACTIONS SECTION.

Drug Interactions. Patients are cautioned on concomitant use of medications that are known to be photosensitizing.

GENERAL PRECAUTIONS SECTION.

General. Test for skin sensitivity before using by applying small amount to an unbroken patch of skin; check within 24 hours. Minor redness is not contraindication, but where there is itching or vesicle formation or excessive inflammatory response further treatment is not advised. Close patient supervision is recommended. Hydroquinone is skin bleaching 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.

HOW SUPPLIED SECTION.

HOW SUPPLIED. Hydroquinone USP, 4% Skin Bleaching Cream is available as follows:1 oz (28.35 g) tube (NDC 42582-700-01). Store at 20-25C (68-77F) [see USP Controlled Room Temperature].

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. Hydroquinone USP, 4% Skin Bleaching Cream is indicated for the gradual bleaching of hyperpigmented skin conditions such as chloasma, melasma, freckles, senile lentigines, and other unwanted areas of melanin hyperpigmentation.

INFORMATION FOR PATIENTS SECTION.

Information for Patients. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight sustains melanocytic activity. To prevent repigmentation, during treatment and maintenance therapy, sun exposure on treated skin should be avoided by application of broad spectrum sunscreen (SPF 15 or greater) or by use of protective clothing.Avoid contact with eyes and mucous membranes.Keep this and all medications out of reach of children. In case of accidental ingestion, call physician or poison control center immediately.

NURSING MOTHERS SECTION.

Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when topical hydroquinone is administered to nursing woman.

OVERDOSAGE SECTION.

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 transient skin reddening and mild burning sensation which does not preclude treatment.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 28.35 Tube Carton. Rx onlyBi-Coastal Pharma International LLCNDC 42582-700-01 Hydroquinone USP, 4% Skin Bleaching CreamNet Wt oz (28.35 g). PRINCIPAL DISPLAY PANEL 28.35 Tube Carton.

PRECAUTIONS SECTION.

PRECAUTIONS. (see WARNINGS). General. Test for skin sensitivity before using by applying small amount to an unbroken patch of skin; check within 24 hours. Minor redness is not contraindication, but where there is itching or vesicle formation or excessive inflammatory response further treatment is not advised. Close patient supervision is recommended. Hydroquinone is skin bleaching 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.. Information for Patients. Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight sustains melanocytic activity. To prevent repigmentation, during treatment and maintenance therapy, sun exposure on treated skin should be avoided by application of broad spectrum sunscreen (SPF 15 or greater) or by use of protective clothing.Avoid contact with eyes and mucous membranes.Keep this and all medications out of reach of children. In case of accidental ingestion, call physician or poison control center immediately.. Drug Interactions. Patients are cautioned on concomitant use of medications that are known to be photosensitizing.. Carcinogenesis, Mutagenesis, Impairment of Fertility. Studies of hydroquinone in animals have demonstrated some evidence of carcinogenicity. The carcinogenic potential of hydroquinone in humans is unknown. Published studies have demonstrated that hydroquinone is mutagen and clastogen. Treatment with hydroquinone has resulted in positive findings for genetic toxicity in the Ames assay in bacterial strains sensitive to oxidizing mutagens, in in vitro studies in mammalian cells, and in the in vivo mouse micronucleus assay.. Pregnancy. Teratogenic Effects. Pregnancy Category C. Animal reproduction studies have not been conducted with topical hydroquinone. It is also not known whether topical hydroquinone can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. Topical hydroquinone should be given to pregnant woman only if clearly needed.. Nursing Mothers. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when topical hydroquinone is administered to nursing woman.. Pediatric Use. Safety and effectiveness for pediatric patients below the age of 12 years have not been established.

PREGNANCY SECTION.

Pregnancy. Teratogenic Effects. Pregnancy Category C. Animal reproduction studies have not been conducted with topical hydroquinone. It is also not known whether topical hydroquinone can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. Topical hydroquinone should be given to pregnant woman only if clearly needed.

REFERENCES SECTION.

REFERENCES. DENTON C., LERNER A.B., FITZPATRICK T.B.Inhibition of Melanin Formation by Chemical Agents Journal of Investigative Dermatology 1952, 18:119-135.2 JIMBOW K., OBATA H., PATHAK M., FITZPATRICK T.B.Mechanism of Depigmentation by Hydroquinone Journal of Investigative Dermatology 1974, 62:436-449.3 PARRISH J.A., ANDERSON R.R., URBACH F., PITTS D. UVA, Biological Effects of Ultraviolet Radiation with Emphasis on Human Responses to Longwave Ultraviolet Plenum Press, New York and London, 1978, p. 151.

SPL UNCLASSIFIED SECTION.

Skin Bleaching Cream Rx only FOR EXTERNAL USE ONLYNOT FOR OPHTHALMIC USE.

STORAGE AND HANDLING SECTION.

Store at 20-25C (68-77F) [see USP Controlled Room Temperature].

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects. Pregnancy Category C. Animal reproduction studies have not been conducted with topical hydroquinone. It is also not known whether topical hydroquinone can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. Topical hydroquinone should be given to pregnant woman only if clearly needed.

WARNINGS SECTION.

WARNINGS. Contains sodium metabisulfite, sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people. Since this product contains no sunscreen, an effective broad spectrum sun blocking agent should be used and unnecessary solar exposure avoided, or protective clothing should be worn to cover bleached skin in order to prevent repigmentation from occurring. Hydroquinone may produce exogenous ochronosis, gradual blue-black darkening of the skin. If this condition occurs, discontinue treatment and consult your physician. The majority of patients developing this condition are Black, but it may also occur in Caucasians and Hispanics.