RENOVA

RENOVA ® (tretinoin cream) 0.02% contains the active ingredient tretinoin in a cream base. Tretinoin is a yellow to light-orange crystalline powder having a characteristic floral odor. Tretinoin is soluble in dimethylsulfoxide, slightly soluble in polyethylene glycol 400, octanol, and 100% ethanol. It is practically insoluble in water and mineral oil, and it is insoluble in glycerin. The chemical name for tretinoin is (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid. Tretinoin is also referred to as all-trans-retinoic acid and has a molecular weight of 300.44. The structural formula is represented below: Tretinoin is available as RENOVA at a concentration of 0.02% w/w in an oil-in-water emulsion formulation consisting of benzyl alcohol, butylated hydroxytoluene, caprylic/capric triglyceride, cetyl alcohol, edetate disodium, methylparaben, propylparaben, purified water, stearic acid, stearyl alcohol, steareth 2, steareth 20, and xanthan gum. chemstructure.jpg

(To understand fully the indication for this product, please read the entire INDICATIONS AND USAGE section of the labeling.) RENOVA (tretinoin cream) 0.02% is indicated as an adjunctive agent (see second bullet point below) for use in the mitigation (palliation) of fine facial wrinkles in patients who use comprehensive skin care and sunlight avoidance programs. RENOVA (tretinoin cream) 0.02% DOES NOT ELIMINATE WRINKLES, REPAIR SUN-DAMAGED SKIN, REVERSE PHOTOAGING, or RESTORE MORE YOUTHFUL or YOUNGER SKIN. In double-blind, vehicle-controlled clinical studies, many patients in the vehicle group achieved desired palliative effects on fine wrinkling of facial skin with the use of comprehensive skin care and sunlight avoidance programs including sunscreens, protective clothing, and non-prescription emollient creams. RENOVA (tretinoin cream) 0.02% has NOT DEMONSTRATED A MITIGATING EFFECT on significant signs of chronic sunlight exposure such as coarse or deep wrinkling, tactile roughness, mottled hyperpigmentation, lentigines, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia, or dermal elastosis. RENOVA (tretinoin cream) 0.02% should be used under medical supervision as an adjunct to a comprehensive skin care and sunlight avoidance program that includes the use of effective sunscreens (minimum SPF of 15) and protective clothing. Patients with visible actinic keratosis and patients with a history of skin cancer were excluded from clinical trials of RENOVA (tretinoin cream) 0.02%. Thus the effectiveness and safety of RENOVA (tretinoin cream) 0.02% in these populations are not known at this time. Neither the safety nor the effectiveness of RENOVA (tretinoin cream) 0.02% for the prevention or treatment of actinic keratoses or skin neoplasms has been established. Neither the safety nor the efficacy of using RENOVA (tretinoin cream) 0.02% daily for greater than 52 weeks has been established, and daily use beyond 52 weeks has not been systematically and histologically investigated in adequate and well-controlled trials (see WARNINGS ). Clinical Trials Four adequate and well-controlled multi-center trials and one single-center randomized, controlled trial were conducted involving a total of 324 evaluable patients treated with RENOVA (tretinoin cream) 0.02% and 332 evaluable patients treated with the vehicle cream on the face for 24 weeks with a comprehensive skin care and sun avoidance program, to assess the effects on fine and coarse wrinkling, mottled hyperpigmentation, tactile skin roughness, and laxity. Patients were evaluated at baseline on a 10-unit scale and changes from that baseline rating were categorized as follows: Worsening: Increase of 1 unit or more. No improvement: No change. Minimal improvement: Reduction of 1 unit. Mild improvement: Reduction of 2 units. Moderate improvement: Reduction of 3 units or more. In these trials, the fine and coarse wrinkling, mottled hyperpigmentation, tactile roughness, and laxity of the facial skin were thought to be caused by multiple factors which included intrinsic aging or environmental factors, such as chronic sunlight exposure. Two of the five trials provided adequate demonstration of efficacy for mitigation of fine facial wrinkling. No two of the five trials adequately demonstrated efficacy for mitigation of coarse wrinkling, mottled hyperpigmentation, tactile skin roughness, and laxity. Data for fine wrinkling (the indication for which RENOVA (tretinoin cream) 0.02% demonstrated efficacy) from all five trials (four studies in lightly pigmented subjects with Fitzpatrick Skin Types I-III and one study in darkly pigmented subjects with Fitzpatrick Skin Types IV-VI) is provided below: FINE WRINKLING IN LIGHTLY PIGMENTED SUBJECTS Subjects Using RENOVA (tretinoin cream) 0.02% + CSP * (N=279) Vehicle + CSP * (N=280) A single-center study (N=107) in darkly pigmented, mostly African-American, subjects with Fitzpatrick Skin Types IV-VI demonstrated minimal or mild improvement in fine facial wrinkling in 43% of patients using Vehicle + CSP compared to 29% of subjects using RENOVA (tretinoin cream) 0.02% + CSP * . Although fewer darkly pigmented subjects improved with RENOVA (tretinoin cream) 0.02% than with vehicle, these findings may reflect the small size of this study. * CSP – Comprehensive skin protection and sunlight avoidance programs including use of sunscreens, protective clothing, and non-prescription emollient creams. Worsened 1% 3% No Change 40% 58% Minimal Improvement 35% 27% Mild Improvement 15% 9% Moderate Improvement 10% 3% Self-assessment of fine wrinkles after 24 weeks of treatment with either RENOVA (tretinoin cream) 0.02% or Vehicle from the four studies in lightly pigmented patients showed the following: No studies have been conducted comparing the facial irritation or efficacy of RENOVA (tretinoin cream) 0.02% to RENOVA (tretinoin cream) 0.05% (older marketed formulation). Patients may lose some of the mitigating effects of RENOVA (tretinoin cream) 0.02% after 12 weeks of discontinuation of RENOVA (tretinoin cream) 0.02% from their comprehensive skin care and sunlight avoidance program. figure1.jpg

Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is pregnant or is attempting to become pregnant or is at high risk of pregnancy. Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is sunburned or if the patient has eczema or other chronic skin conditions of the face. Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is inherently sensitive to sunlight. Do NOT use RENOVA (tretinoin cream) 0.02% if the patient is also taking drug(s) known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the possibility of augmented phototoxicity. Patients require detailed instruction to obtain maximal benefits and to understand all the precautions necessary to use this product with greatest safety. The physician should review the Patient Package Insert. RENOVA (tretinoin cream) 0.02% should be applied to the face once a day in the evening, using only enough to cover the entire affected area lightly. Patients should gently wash their faces with a mild soap, pat the skin dry, and wait 20 to 30 minutes before applying RENOVA (tretinoin cream) 0.02%. The patient should apply a small pearl-sized (about ¼ inch or 5 mm diameter) amount of cream to cover the entire affected area lightly. Caution should be taken when applying the cream to avoid the eyes, ears, nostrils, and mouth. Application of RENOVA (tretinoin cream) 0.02% may cause a transitory feeling of warmth or slight stinging. Mitigation (palliation) of fine facial wrinkling may occur gradually over the course of therapy. Up to 6 months of therapy may be required before the effects are seen. With discontinuation of RENOVA (tretinoin cream) 0.02% therapy, some patients may lose the mitigating effects of RENOVA (tretinoin cream) 0.02% on fine facial wrinkles. The safety and effectiveness of using RENOVA (tretinoin cream) 0.02% daily for greater than 52 weeks have not been established. Application of larger amounts of medication than recommended may not lead to more rapid or better results, and marked redness, peeling, or discomfort may occur. Patients treated with RENOVA (tretinoin cream) 0.02% may use cosmetics but the areas to be treated should be cleansed before the medication is applied (see PRECAUTIONS ).

This drug is contraindicated in individuals with a history of sensitivity reactions to any of its components. It should be discontinued if hypersensitivity to any of its ingredients is noted.

(See WARNINGS and PRECAUTIONS .) In double-blind, vehicle-controlled studies involving 339 patients who applied RENOVA (tretinoin cream) 0.02% to their faces, adverse reactions associated with the use of RENOVA (tretinoin cream) 0.02% were limited primarily to the skin. Almost all patients reported one or more local reactions such as peeling, dry skin, burning, stinging, erythema, and pruritus. In 32% of all study patients, skin irritation was reported that was severe, led to temporary discontinuation of RENOVA (tretinoin cream) 0.02%, or led to use of a mild topical corticosteroid. About 7% of patients using RENOVA (tretinoin cream) 0.02%, compared to less than 1% of the control patients, had sufficiently severe local irritation to warrant short-term use of mild topical corticosteroids to alleviate local irritation. About 4% of patients had to discontinue use of RENOVA (tretinoin cream) 0.02% because of adverse reactions. Approximately 2% of spontaneous postmarketing adverse event reporting for RENOVA (tretinoin cream) 0.05% were for skin hypo- or hyperpigmentation. Other spontaneously reported adverse events for RENOVA (tretinoin cream) 0.05% predominantly appear to be local reactions similar to those seen in clinical trials. To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Concomitant topical medications, medicated or abrasive soaps, shampoos, cleansers, cosmetics with a strong drying effect, products with high concentrations of alcohol, astringents, spices or lime, permanent wave solutions, electrolysis, hair depilatories or waxes, and products that may irritate the skin should be used with caution in patients being treated with RENOVA (tretinoin cream) 0.02% because they may increase irritation with RENOVA (tretinoin cream) 0.02%. RENOVA (tretinoin cream) 0.02% should not be administered if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the possibility of augmented phototoxicity.

Storage: Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).