TRETINOIN

Tretinoin Gel, 0.05% is a translucent to opaque, pale yellow gel containing 0.05% tretinoin, by weight for topical administration. Chemically, tretinoin is all- trans -retinoic acid, also known as (all- E )-3,7-dimethyl-9-(2,6,6-trimethyl-1- cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid. It is a member of the retinoid class of compounds, and a metabolite of Vitamin A. Tretinoin has a molecular weight of 300.44, a molecular formula of C 20 H 28 O 2 and the following structure: Each gram of Tretinoin Gel, 0.05% contains 0.5 mg of tretinoin. Other components of this formulation are benzyl alcohol, butylparaben, butylated hydroxytoluene, carbomer homopolymer Type C, ethylparaben, fish collagen hydrolyzates, glycerin, isobutylparaben, methylparaben, octoxynol 9, phenoxyethanol, propylparaben, purified water, sodium hyaluronate, and trolamine. The contribution to efficacy of individual components of the vehicle has not been evaluated. chemstructure

Tretinoin Gel is indicated for topical treatment of acne vulgaris. Tretinoin Gel is a retinoid indicated for topical treatment of acne vulgaris. ( 1 )

For topical use only. Not for ophthalmic, oral, or intravaginal use. Tretinoin Gel should be applied once daily, before bedtime, to the skin where acne lesions appear, using a thin layer to cover the entire affected area. Tretinoin Gel should be kept away from the eyes, the mouth, paranasal creases, and mucous membranes. Application of excessive amounts of gel will not provide incremental efficacy. Patients treated with Tretinoin Gel may use cosmetics, but the areas to be treated should be cleansed thoroughly before the medication is applied. When treating with Tretinoin Gel, caution should be exercised with the use of concomitant topical over-the-counter preparations, topical medications, medicated or abrasive soaps and cleansers, products that have strong drying effect, and products with high concentrations of alcohol, astringents, spices, or lime. Particular caution should be exercised with acne preparations containing benzoyl peroxide, sulfur, resorcinol, or salicylic acid. Allow the effects of such preparations to subside before use of Tretinoin Gel has begun. • Apply a thin layer of Tretinoin Gel once daily, before bedtime, to skin where lesions occur. Keep away from eyes, mouth, nasal creases, and mucous membranes. ( 2 ) • Tretinoin Gel is not for oral, ophthalmic, or intravaginal use. ( 2 )

None. None ( 4 )

The most common adverse reactions (incidence ≥5%) with Tretinoin Gel are dry skin, peeling/scaling/flaking skin, skin burning sensation, and erythema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Obagi Cosmeceuticals LLC at 1-800-636-7546 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under prescribing conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In two randomized, controlled trials, 674 subjects received treatment for up to 12 weeks with Tretinoin Gel [see Clinical Studies (14) ] .In these studies, 50% of the subjects who were treated with Tretinoin Gel reported one or more adverse reactions; 30% of the subjects reported treatment-related adverse reactions. In the vehicle group, 29% of the 487 randomized subjects reported at least one adverse reaction; 5% of the subjects reported events that were treatment-related. There were no serious, treatment-related adverse reactions reported by subjects in any of the treatment groups. Selected adverse reactions that occurred in at least 1% of subjects in the two trials combined are shown in Table 1 (below). Most skin-related adverse reactions first appear during the first two weeks of treatment with Tretinoin Gel, and the incidence rate for skin-related reactions peaks around the second and third week of treatment. In some subjects, the skin-related adverse reactions persist throughout the treatment period. Table 1: Number of Subjects with Selected Adverse Reactions (Occurring in at Least 1% of Subjects) Event Tretinoin Gel (n = 674) Vehicle Gel (n = 487) Dry Skin 109 (16%) 8 (2%) Peeling/Scaling/Flaking Skin 78 (12%) 7 (1%) Skin Burning Sensation 53 (8%) 8 (2%) Erythema 47 (7%) 1 (<1%) Pruritus 11 (2%) 3 (1%) Pain of Skin 7 (1%) 0 (0%) Sunburn 7 (1%) 3 (1%) 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Tretinoin Gel. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Temporary hyper- or hypopigmentation has been reported with repeated application of tretinoin.

Storage and Handling: Store at controlled room temperature 20° to 25°C (68° to 77°F) with excursions permitted between 15° to 30°C (59° to 86°F). Protect from freezing. Keep out of reach of children.