RxMed: Pharmaceutical Information – RENOVA

RENOVA®

Janssen-Ortho

Tretinoin

Agent for the Treatment of Photodamaged Skin

Action And Clinical Pharmacology: Tretinoin significantly reduces clinical signs of photodamaged skin such as fine wrinkles, mottled hyperpigmentation and roughness.

While the exact mechanism of action of tretinoin is unknown, the clinical improvements are accompanied by the following histologic changes: increased epidermal and granular layer thickness, reduced melanin content and stratum corneum alterations.

Indications And Clinical Uses: For the treatment of fine wrinkling, mottled hyperpigmentation and roughness of the skin. These signs are usually associated with photodamaged (sun-damaged) skin and intrinsic aging but may be associated with other conditions.

The safety and efficacy of tretinoin for the prevention or treatment of actinic or solar keratoses have not been established.

Contra-Indications: 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. tag_WarningWarnings

Manufacturers’ Warnings In Clinical States: Tretinoin should be used under medical supervision as part of a comprehensive skin protection program, including use of sunscreen products and protective clothing.

Excessive use of tretinoin should be avoided. Tretinoin should be kept away from the eyes, mouth, angles of the nose or mucous membranes. Topical use may induce severe local erythema, pruritus, burning or stinging and peeling at the site of application. If the degree of local irritation warrants, patients should be directed to use the medication less frequently, discontinue use temporarily, or discontinue use altogether.

Tretinoin has been reported to cause severe irritation on eczematous skin and should be used with utmost caution in patients with this condition.

Pregnancy : Topical tretinoin should be used by women of childbearing years only after contraceptive counselling. It is recommended that topical tretinoin should not be used by pregnant women.

There have been a few reports of birth defects among babies born to women exposed to topical tretinoin during pregnancy. To date, there have been no adequate and well-controlled prospective studies performed in pregnant women, and the teratogenic blood level of tretinoin is unclear. However, a retrospective cohort study of babies born to women exposed to topical tretinoin during the first trimester of pregnancy found no excess birth defects among these babies when compared with babies born to women in the same cohort who were not similarly exposed.

Oral tretinoin has been shown to be teratogenic and fetotoxic in rats when given in doses 1 000 and 500 times the topical human dose, respectively.

In 9 out of 10 topical teratology studies of tretinoin conducted in rats and rabbits using several formulations, there has been no evidence of teratogenicity. In 1 out of 10 studies, there was an increase in fetal malformations; however, a clear causal relationship of topical tretinoin and these findings could not be established. In a repeat of this study, there were no fetal malformations. Topical tretinoin can produce treatment-related fetal effects (delayed ossification of bones and an increase in supernumerary ribs). The fetal no effect dose is 1 mg/kg/day (200 times the recommended clinical dose).

Lactation : It is not known whether tretinoin is excreted in human milk. Nevertheless, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Children: Safety and effectiveness in children have not been established.

Precautions: General: If a reaction suggesting sensitivity, chemical irritation, or a systemic adverse effect should occur, use of tretinoin should be discontinued.

Exposure to sunlight, including sunlamps, should be avoided or minimized during the use of tretinoin, and patients with sunburn should be advised not to use the product until fully recovered because of heightened susceptibility to sunlight as a result of the use of tretinoin. Patients who may be required to have considerable sun exposure due to occupation and those inherently sensitive to the sun should exercise particular caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with tretinoin.

Carcinogenesis: The mutagenic potential of tretinoin was evaluated in the Ames assay and the in vivo mouse micronucleus assay, both of which were negative. In a lifetime study of topical tretinoin in CD-1 mice, there was no evidence of carcinogenic potential. Studies in hairless albino mice suggest that tretinoin may accelerate the tumorigenic potential of weakly carcinogenic light from a solar simulator. Although the significance of these studies to man is not clear, patients should avoid or minimize exposure to sun.

Information for the Patient: A patient information leaflet has been prepared and is included with each package of Renova emollient cream (see Blue Section – Information for the Patient “Renova”). The skin of certain sensitive individuals may become excessively red, swollen, blistered, or crusted. Tretinoin should be discontinued if patients experience severe or persistent irritation, and they should be advised to consult their physician.

Drug Interactions: Concomitant topical medication, medicated or abrasive soaps, shampoos and cleansers, cosmetics that have a strong drying effect, and products with high concentrations of alcohol, as well as astringents and products that may irritate the skin, should be used with caution because they may increase irritation with tretinoin.

Adverse Reactions: In double-blind, vehicle-controlled studies involving 199 patients who received tretinoin for facial photodamage, adverse reactions associated with the use of tretinoin emollient cream were limited primarily to the skin. Local reactions such as peeling or dry skin, burning or stinging, erythema, and pruritus were reported by most subjects during therapy with tretinoin emollient cream. These signs and symptoms were usually of mild to moderate severity and were generally well tolerated. These skin reactions occurred early in therapy and, except for dryness and peeling which tended to persist during therapy, generally decreased over the course of therapy.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Tretinoin emollient cream is indicated for topical use only. If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Oral ingestion of this drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A. tag_DosageDosage

Dosage And Administration: The emollient cream should be applied once daily at bedtime, to lightly cover the entire face. In some cases it has been necessary to temporarily discontinue therapy or to reduce the frequency of application. When the patient is able to tolerate the treatment, therapy can be resumed or the frequency of application can be increased.

Improvement in facial photodamage with tretinoin treatment occurs gradually over the course of therapy. Six months of therapy may be required before definite beneficial effects are seen.

Patients treated with tretinoin should use an effective sunscreen with a minimum SPF of 15 as well as protective clothing when exposure to the sun cannot be avoided.

Availability And Storage: Each g of yellow cream with a characteristic floral odor contains: tretinoin 0.5 mg w/w. Nonmedicinal ingredients: citric acid (monohydrate), butylated hydroxytoluene, dimethicone 50cs, edetate disodium, fragrance, hydroxyoctacosanyl hydroxystearate, light mineral oil, methoxy PEG-22/dodecyl glycol copolymer, methylparaben, PEG-45/dodecyl glycol copolymer, purified water, quaternium-15, sorbitol solution, stearoxytrimethyl-silane and stearyl alcohol. Tubes of 20 g. Store between 15 and 25°C. Do not freeze.

RENOVA® Janssen-Ortho Tretinoin Agent for the Treatment of Photodamaged Skin