Retin-A (Tretinoin)

RETIN-A®

Janssen-Ortho

Tretinoin

Comedolytic Agent

Action And Clinical Pharmacology: Studies in animals have shown that tretinoin supplies all the physiologic requirements of vitamin A except those needed for vision and reproduction. When animals were fed a diet in which vitamin A was replaced by vitamin A acid, there was no storage in the liver. This suggests that the acid may be the tissue-active form which is important for epithelial growth and general health, while the alcohol or ester form is necessary for vision and reproduction.

Repeated skin applications of vitamin A acid over a period of days have produced detectable changes in the skin. Initially, the change is mild erythema, followed by flaking or peeling of the stratum corneum, which in itself is associated with a marked thinning of the stratum corneum and increased cellular turnover in the skin.

Local application of vitamin A has been reported to have reduced abnormal cornification in follicular orifices, and vitamin A acid was reported to be more potent than vitamin A alcohol or its esters when applied locally in ointments to human skin.

Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells, causing extrusion of the comedones.

Indications And Clinical Uses: For topical application in the treatment of acne vulgaris.

Contra-Indications: Patients who have demonstrated a hypersensitivity to the drug. tag_WarningWarnings

Manufacturers’ Warnings In Clinical States: General: Excessive use of tretinoin should be avoided. In order to minimize the potential for additional skin irritation, care should be taken to avoid contact with the eyes, eyelids, angles of the nose, mouth, mucous membranes or other areas where treatment is not intended. Tretinoin may cause irritation of circumoral and other sensitive skin areas. Tretinoin should not be applied to severely inflamed skin or to open lesions.

Simultaneous use of harsh abrasives and other skin treatments, including sun lamp, should be avoided if possible.

In some patients temporary skin irritation may occur, especially in early weeks of treatment. Should these reactions occur to an excessive degree, and the skin becomes extremely red, swollen and crusted, use of tretinoin should be discontinued immediately.

An apparent exacerbation may develop due to the drug effect on previously seen deep lesions. This is an anticipated part of the therapeutic effect. Therapy should be continued.

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 not clear. However, a well-conducted 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 in 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. Since many drugs are excreted in human milk, caution should be exercised when tretinoin is administered to a nursing mother.

Precautions: General: For external use only.

Cosmetics may be used, but the areas to be treated should be cleansed thoroughly before the medication is applied. Astringent toiletries should be avoided.

Patients will be able to remove hair as usual (e.g., plucking, electrolysis, depilatories) but should avoid these procedures at night before applying tretinoin as they might result in skin irritation.

Permanent wave solutions, waxing preparations, medicated soaps and shampoos can sometimes irritate even normal skin. Caution should be used so that these products do not come into contact with skin treated with tretinoin.

Exposure to sunlight, including ultraviolet sunlamps, may provoke additional irritation. Therefore, exposure should be avoided or minimized during the use of tretinoin. A patient experiencing considerable sun exposure due to occupational duties, and/or any patient 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.

Hyper- or hypopigmentation has occasionally been reported when the product is used to the point of producing severe irritation. This is reversible when the medication is stopped.

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

Gels are flammable. Note: Keep away from heat and flame. Keep tube tightly closed.

Local Irritation: It is not recommended to initiate treatment with tretinoin or continue its use in the presence of skin irritation (e.g., erythema, peeling, pruritus, sunburn, etc.) until these symptoms subside.

In certain sensitive individuals, tretinoin may induce severe local erythema, swelling, pruritus, warmth, burning or stinging, blistering, crusting and/or peeling at the site of application. If the degree of local irritation warrants, the patient should be instructed to either apply the medication less frequently or discontinue its use temporarily.

Tretinoin has been reported to cause severe irritation on eczematous skin and should be used with utmost caution in patients with this condition. If a patient experiences severe or persistent irritation, the patient should be advised to discontinue application of tretinoin completely, and if necessary, consult a physician.

Weather extremes, such as wind, cold and low humidity may be irritating to skin treated with tretinoin and may increase its dryness.

Drug Interactions: Concomitant topical medication, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices or lime should be used with caution because of possible interaction with tretinoin. Particular caution should be exercised in using preparations containing sulfur, resorcinol, or salicylic acid with tretinoin. It is also advisable to “rest” a patient’s skin until the effects of such preparations subside before use of tretinoin is begun.

Adverse Reactions: Some degree of local irritation is expected. The most commonly reported undesirable effects are dry skin, burning, stinging, warmth, erythema, pruritus, rash, peeling and temporary hypo- and hyperpigmentation. Rarely reported undesirable effects are blistering and crusting of the skin, eye irritation and edema. These reactions were usually mild to moderate in severity, generally well-tolerated and self-limiting, occurred early during the course of therapy and generally decreased over time with the exception of dry skin, which tended to persist.

True contact allergy to topical tretinoin is rarely encountered.

Changes in the skin may be anticipated, indicating an active effect of the medication. Expected changes include mild erythema and flaking or peeling of the stratum corneum. In certain very sensitive patients, the skin may become very erythematous, edematous, blistered or crusted. In such cases, application of tretinoin should be discontinued until the skin has fully recovered. Further applications should be at a level that the individual can tolerate. All adverse reactions observed are reversible when treatment is discontinued.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: If medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. Tretinoin is intended for topical use only. In the event of accidental ingestion, if the ingestion is recent, the stomach should be emptied immediately by gastric lavage or by induction of emesis. All other treatment should be appropriately supportive. Oral ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of vitamin A including teratogenesis in women of childbearing years. Therefore, in such cases pregnancy testing should be carried out in women of childbearing years. Reduce amount or frequency of application if undesirable reactions occur.

Dosage And Administration: Excessive use should be avoided.

Adults: Apply daily to the affected areas, preferably at bedtime, after cleansing with a mild, nonmedicated soap and water. The treated area should be washed no more than twice per day. After washing, the skin should be dried gently and completely without rubbing it. Allow at least 20 to 30 minutes to dry before applying medication. Only a sufficient quantity of medication should be applied to cover the affected areas lightly, using a gauze swab, cotton wool or the tips of clean fingers. Over-saturation should be avoided since excess medication could run into the eyes, angles of the nose or other areas where treatment is not intended.

Discontinue treatment if a severe local inflammatory response is experienced. Reinstitute therapy when the reaction has subsided and apply preparation every other day or less frequently. Should discomfort still be experienced, stop treatment completely.

Maintenance dose should be the least number of applications that will prevent recurrence of the condition. Maintenance therapy should be administered daily for best results.

Application of tretinoin may cause a transitory feeling of warmth or slight stinging. When administered according to recommended guidelines, tretinoin may produce a slight erythema similar to that of mild sunburn. In cases where it is necessary to temporarily discontinue therapy or reduce the frequency of application, therapy should be resumed or the frequency of application increased when the patient becomes able to tolerate the treatment.

Excess application of tretinoin does not provide more rapid or better results. In fact, marked redness, peeling or discomfort can occur. If excess application occurs accidentally or through over-enthusiastic use, tretinoin should be discontinued for several days before resuming therapy.

Therapeutic effects may be noticed after 2 to 3 weeks of use but more than 6 weeks of therapy may be required before definite beneficial effects are seen. During the early weeks of treatment, an apparent exacerbation of inflammatory lesions may occur. This is due to the action of the medication on deep, previously unseen lesions and should not be considered a reason to discontinue therapy. Once a satisfactory response has been obtained, it may be possible to maintain this improvement with less frequent applications.

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

Availability And Storage: Cream: Each g of smooth, yellow, oil-in-water cream, contains: tretinoin 0.01%, 0.025%, 0.05% or 0.1% in a bland, hydrophilic base. Nonmedicinal ingredients: butylated hydroxytoluene, isopropyl myristate, polyoxyl (40) stearate, purified water, sorbic acid, stearic acid, stearyl alcohol and xanthan gum (Keltrol). Tubes of 30 g.

Gel: Each g of smooth, clear, viscous yellow gel, contains: tretinoin 0.01% or 0.025%. Nonmedicinal ingredients: butylated hydroxytoluene, ethanol undenatured and hydroxypropyl cellulose. Tubes of 30 g.

Keep container closed when not in use. Store between 15 and 25°C.

RETIN-A® Janssen-Ortho Tretinoin Comedolytic Agent

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Acne

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