Renova Information
Renova (Tretinoin)
Renova (Tretinoin) Description:
Renova (Tretinoin) (tretinoin emollient cream) 0.05% contains the active ingredient tretinoin (a retinoid) in an emollient 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-cyclonexen-1-yl)-2,4,6,8-nonatetraenoic acid. Tretinoin is also referred to as all--retinoic acid and has a molecular weight of 300.44. The structural formula is represented below.
Tretinoin is available as Renova (Tretinoin) at a concentration of 0.05% w/w in a water in oil emulsion formulation consisting of light mineral oil, NF; sorbitol solution, USP; hydroxyoctacosanyl hydroxystearate; methoxy PEG-22/dodecyl glycol copolymer; PEG-45/dodecyl glycol copolymer; stearoxytrimethylsilane and stearyl alcohol; dimethicone 50 cs; methylparaben, NF; edetate disodium, USP; quaternium-15; butylated hydroxytoluene, NF; citric acid monohydrate, USP; fragrance; and purified water, USP.
Renova (Tretinoin) Clinical Pharmacology:
The exact mechanism of action of tretinoin is unknown although retinoids are believed to exert an effect on the growth and differentiation of various epithelial cells. When applied topically, however, there was no noted increase in desmosine, hydroxyproline, or elastin mRNA in human skin. In addition, the role of the irritative nature of this product in effecting the positive effects attributed to this product for its indication has not yet been fully determined.
The transdermal absorption of tretinoin from various topical formulations ranged from 1% to 31% of applied dose, depending on whether it was applied to healthy skin or dermatitic skin. When percutaneous absorption of Renova (Tretinoin) was assessed in healthy male subjects (n=14) after a single application, as well as after repeated daily applications for 28 days, the absorption of tretinoin was less than 2% and endogenous concentrations of tretinoin and its major metabolites were unaltered.
Renova (Tretinoin) Indications And Usage:
Renova (Tretinoin) (tretinoin emollient cream) 0.05% is indicated as an adjunctive agent (see second bullet point below) for use in the mitigation (palliation) of wrinkles, mottled hyperpigmentation, and tactile roughness of facial skin in patients who do not achieve such palliation using comprehensive skin care and sun avoidance programs alone (see bullet point 3 for populations in which effectiveness has not been established). Many patients achieve desired palliative effects on fine wrinkling, mottled hyperpigmentation, and tactile roughness of facial skin with the use of comprehensive skin care and sun avoidance programs including sunscreens, protective clothing, and emollient creams containing tretinoin.
Renova (Tretinoin) Contraindications:
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.
Renova (Tretinoin) Warnings:
Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided or minimized during use of Renova (Tretinoin) . Patients must be warned to use sunscreens (minimum SPF of 15) and protective clothing when using Renova (Tretinoin) . Patients with sunburn should be advised not to use Renova (Tretinoin) until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using Renova (Tretinoin) and assure that the precautions outlined in the are observed.
Renova (Tretinoin) should be kept out of the eyes, mouth, angles of the nose, and mucous membranes. Topical use may cause severe local erythema, pruritus, burning, stinging, and peeling at the site of application. If the degree of local irritation warrants, patients should be directed to use less medication, decrease the frequency of application, discontinue use temporarily, or discontinue use altogether.
Tretinoin has been reported to cause severe irritation on eczematous skin and should be used only with utmost caution in patients with this condition.
Application of larger amounts of medication than recommended will not lead to more rapid or better results, and marked redness, peeling, or discomfort may occur.
Renova (Tretinoin) Precautions:
If a drug sensitivity, chemical irritation, or a systemic adverse reaction develops, use of Renova (Tretinoin) should be discontinued.
Weather extremes, such as wind or cold, may be more irritating to patients using Renova (Tretinoin) .
Information for Patients:
Patient Package Insert
Drug Interactions:
Renova (Tretinoin) 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
In a chronic, two-year bioassay of Vitamin A acid in mice performed by Tsubura and Yamamoto, generalized amyloid deposition was reported in all groups in the basal layer of the Vitamin A treated skin. In CD-1 mice, a similar study reported hyalinization at the treated skin sites and the incidence of this finding was 0/50, 3/50, 3/50, and 2/50 in male mice and 1/50, 0/50, 4/50, and 2/50 in female mice from the vehicle control, 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg groups, respectively.
Studies in hairless albino mice suggest that tretinoin may enhance the tumorigenic potential of carcinogenic doses of UVB and UVA light from a solar simulator. In other studies, when lightly pigmented hairless mice treated with tretinoin were exposed to carcinogenic doses of UVB light, the incidence and rate of development of skin tumors were either reduced or no effect was seen. Due to significantly different experimental conditions, no strict comparison of these disparate data is possible at this time. Although the significance of these studies to humans is not clear, patients should minimize exposure to sun.
The mutagenic potential of tretinoin was evaluated in the Ames assay and in the mouse micronucleus assay, both of which were negative.
Dermal Segment I and Ill studies with Renova (Tretinoin) have not been performed in any species. In oral Segment I and Segment Ill studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (>400 times the average recommended human topical clinical dose).
Renova (Tretinoin) Adverse Reactions:
(See and sections.)
In double-blind, vehicle-controlled studies involving 179 patients who applied Renova (Tretinoin) to their face, adverse reactions associated with the use of Renova (Tretinoin) were limited primarily to the skin. During these trials, 4% of patients had to discontinue use of Renova (Tretinoin) because of adverse reactions. These discontinuations were due to skin irritation or related cutaneous adverse reactions.
Local reactions such as peeling, dry skin, burning, stinging, erythema, and pruritus were reported by almost all subjects during therapy with Renova (Tretinoin) . These signs and symptoms were usually of mild to moderate severity and generally occurred early in therapy. In most patients the dryness, peeling, and redness recurred after an initial (24 week) decline.
Renova (Tretinoin) Overdosage:
Application of larger amounts of medication than recommended will not lead to more rapid or better results, and marked redness, peeling, or discomfort may occur. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.
Renova (Tretinoin) Dosage And Administration:
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 .
Renova (Tretinoin) should be applied to the face once a day before retiring using only enough to cover the entire affected area lightly. Patients should gently wash their face with a mild soap, pat the skin dry, and wait 20 to 30 minutes before applying Renova (Tretinoin) . The patient should apply a pea-sized amount of cream to cover the entire face lightly. Special caution should be taken when applying the cream to avoid the eyes, ears, nostrils, and mouth.
Application of Renova (Tretinoin) may cause a transitory feeling of warmth or slight stinging.
Mitigation (palliation) of facial fine wrinkling, mottled hyperpigmentation and tactile roughness may occur gradually over the course of therapy. Up to six months of therapy may be required before the effects are seen. Most of the improvement noted with Renova (Tretinoin) is seen during the first 24 weeks of therapy. Thereafter, therapy primarily maintains the improvement realized during the first 24 weeks.
With discontinuation of Renova (Tretinoin) therapy, a majority of patients will lose most mitigating effects of Renova (Tretinoin) on fine wrinkles, mottled hyperpigmentation, and tactile roughness of facial skin;
Application of larger amounts of medication than recommended will not lead to more rapid or better results, and marked redness, peeling, or discomfort may occur.
Patients treated with Renova (Tretinoin) may use cosmetics but the areas to be treated should be cleansed thoroughly before the medication is applied. (See section.)
Renova (Tretinoin) How Supplied
Renova (Tretinoin) is available in these sizes:
Storage:
QUESTIONS:
Rx only.
DERMATOLOGICAL DIVISIONORTHO PHARMACEUTICAL CORPORATIONRaritan, New Jersey 08869
© OPC 1991;Printed in USA
U.S. Patents 4,603,146, 4,423,041 and 4,877,805 653-10-870-7
