COMPOSITION Each gram of cream contains 0,5 mg tretinoin in a water-in-oil emulsion.
Methyl parahydroxybenzoate 0,2% (w/w)
Quaternium-15 0,1% (w/w)
Antioxidant: Butylhydroxytoluene 0,1% (w/w).
PHARMACOLOGICAL CLASSIFICATION A.13.5 Emollients and protectives.
Pharmacodynamics The mechanism of action of topical tretinoin as a treatment for photodamage is not completely understood. It is, however known that tretinoin activates gene transcription for many important proteins by binding to specific retinoid receptors in the cell nucleus. Ultrastructural studies show an increased number of anchoring fibrils in the papillary dermis of tretinoin-treated photodamaged skin. These molecular events, coupled with the characteristic histologic effects of tretinoin i.e. increased epidermal and granular layer thickness with changes in stratum corneum morphology, indicate a specific effect rather than one induced by irritation, as has been previously suggested. Pharmacokinetics Upon topical application of RENOVA, tretinoin penetrates both the epidermis and dermis. The mean percutaneous absorption following single and repeated applications is less than 2% and physiologic concentrations of tretinoin and its major metabolites are unaltered.
INDICATIONS RENOVA is indicated as adjunctive therapy for the topical treatment of mottled hyperpigmentation, roughness and fine wrinkling of photodamaged skin due to chronic sun exposure in patients who do not achieve improvement with comprehensive skin care programs and sun avoidance measures.
There is no convincing evidence that RENOVA cream eliminates wrinkles, repairs sun damaged skin, reverses photoageing, or restores a more youthful or younger dermatalogical pattern.
CONTRA-INDICATIONS History of sensitivity/hypersensitivity reactions to any of the components.
WARNINGS: The effectiveness of RENOVA has not been established in persons greater than 50 years of age or in people with moderate to heavily pigmented skin.
The safety and efficacy of using RENOVA daily for greater than 48 weeks (12 months) have not been demonstrated in adequate and well-controlled trials.
DOSAGE AND DIRECTIONS FOR USE RENOVA should be applied once daily in the evening in only a sufficient quantity to lightly cover the entire affected areas (face or arms).
Areas to be treated should be cleansed thoroughly. Use of a mild, non-medicated soap is recommended. Pat the skin dry without rubbing. Allow area to dry for at least 20-30 minutes before application of RENOVA to the skin. Twice daily washing of the treated area is more than sufficient.
Application of RENOVA may cause transitory stinging and a feeling of warmth. When RENOVA is administered, it normally produces a slight, transient erythema similar to that of mild sunburn. More frequent application or use of larger quantities of RENOVA will not improve the outcome of treatment, and may induce marked skin irritation, e.g. erythema, peeling, pruritus etc (see SPECIAL PRECAUTIONS).
Cosmetics and moisturizers may be used concurrently throughout the duration of RENOVA therapy. Duration of Treatment: Improvements in signs of photodamage with RENOVA are not immediate but occur gradually over the course of therapy. The onset of visible improvements is variable, however, in general, effects emerge within 3-4 months of initiating treatment. Six months of treatment may be required before definite beneficial effects are seen.
Once the maximum beneficial effects have been achieved, they can be maintained with application of RENOVA one to three times weekly. If maintenance therapy is not used, the beneficial effect achieved will diminish over time.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects Symptoms of local irritation frequently reported during therapy include: dry or peeling skin, burning, stinging, warmth, erythema, pruritus, and temporary hypo- and hyperpigmentation. They usually occur early in therapy and, except for dry or peeling skin which may persist during therapy, generally decrease over the course of treatment.
Heightened susceptibility to either sunlight or other sources of UVB has been reported. Special precautions Localirritation: The presence of skin irritation (e.g. erythema, peeling, pruritus, sunburn etc.) should prohibit initiation or recommencement of treatment with RENOVA until the symptoms subside. If the degree of local irritation warrants, a patient should be directed to apply the medication less frequently or discontinue its use temporarily.
Use of RENOVA in certain sensitive individuals (e.g. patients with eczema, sunburn etc) may induce severe local erythema, swelling' pruritus, warmth, burning or stinging, blistering, crusting and/or peeling at the site of application. Tretinoin has been reported to cause severe irritation of eczematous skin and should be used with utmost caution in patients having this condition. If a patient experiences severe or persistent irritation, the patient should be advised to discontinue application of RENOVA completely and, if necessary, consult a doctor.
Weather extremes, such as wind, cold and low humidity may also be irritating to skin treated with RENOVA and may increase its dryness. Exposure to sunlight: Exposure to sunlight, including ultraviolet (UVB) sunlamps, should be avoided or minimized during the use of tretinoin. Patients with sunburn should be advised not to use the product until fully recovered because of potential severe irritation to sensitive skin. A person who experiences considerable sun exposure due to occupational duties and/or anyone inherently sensitive to the sun should exercise particular caution. When exposure to sunlight cannot be avoided, use of sunscreen products and protective clothing over treated areas is recommended. Precautions for use: RENOVA should be used under medical supervision as part of a comprehensive skin care program, including patient education regarding sun avoidance and general skin care, use of sunscreens and moisturizing products, and protective clothing.
Care should be taken to avoid contact with the eyes, eyelids, angles of the nose, mouth, mucous membranes or other areas were treatment is not intended, in order to minimize the potential for additional skin irritation. Carcinogenesis: The weight of evidence indicates that topical tretinoin is not carcinogenic. Studies in hairless albino mice suggest that tretinoin may accelerate the tumorigenic potential of UVB 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 photocarcinogenic effects of tretinoin were not observed. Due to significantly different experimental conditions, no strict comparison of these disparate data is possible. Although the significance of these studies in man is not clear, patients should avoid or minimize exposure to sunlight.
The weight of evidence suggests that topical tretinoin is not mutagenic. Pregnancy and Lactation In clinical trials with RENOVA, the topical human dose used in a 50 kg adult applying a maximum volume of 500 mg of 0,05% cream was 0,005 mg/kg. In animal reproductive studies, oral tretinoin is known to be teratogenic and has been shown to be fetotoxic in rats when given in doses 500 times the topical human dose. In reproduction studies in rats and rabbits, topical tretinoin, when used at doses 1000 times the topical human dose, induced minor skeletal abnormalities, eg. irregularly contoured or partially ossified skull bones. These changes may be considered variants of normal development and are usually corrected after weaning.
There are no adequate and well-controlled studies in pregnant women. Therefore, RENOVA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether tretinoin is excreted in human milk. Therefore, caution should be exercised when RENOVA is administered to a nursing mother. Interactions Use RENOVA with caution in the presence of:
- concomitant topical medications
- toiletry preparations having an abrasive, drying or desquamative effect, including soaps, shampoos, cosmetics, perfumes and astringents (especially those containing alcohol, lime or spices).
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF IT TREATMENT Excessive application of RENOVA does not improve the results of treatment and may induce marked irritation, e.g. erythema, peeling, pruritus etc. Oral ingestion of RENOVA may lead to similar side effects as those associated with excessive oral intake of Vitamin A (e.g. pruritus, dry skin, arthralgia, anorexia, vomiting).
IDENTIFICATION Yellow cream with a characteristic floral odour.
PRESENTATION RENOVA (tretinoin) cream is packed in aluminium tubes containing 20 g cream.
STORAGE INSTRUCTIONS Store below 25°C. DO NOT FREEZE.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER 30/13.5/0020
NAME AND BUSINESS ADDRESS OF APPLICANT JANSSEN PHARMACEUTICA (PTY) LTD
(Reg. No. 80/11122/07)