Action And Clinical Pharmacology: The precise mechanism of action of tretinoin on the skin is not fully understood. It is known that tretinoin is both pharmacologically and structurally related to vitamin A which regulates epithelial cell growth and differentiation. Tretinoin itself is known to have an irritant and keratolytic effect on the skin. These 2 actions which occur simultaneously have been shown histologically in both animal and man to be associated with an increased growth rate and with a decrease in the cohesiveness of the epidermal cells. The result is a slightly thickened epidermis with an accelerated turnover rate and shedding of keratinized cells as very fine barely perceptible scales.
In acne vulgaris the induced fine scaling of the skin surface is accompanied by an increased production of less cohesive epidermal sebaceous cells which consequently flow out of the follicle at a more rapid rate. The thickened mass of sebaceous cellular debris, the comedones, appear to be initially extruded and then prevented from recurring by these actions. Histopathologically, acne is the impaction plus distention of the sebaceous follicles by tightly packed horny cells and disruption of the follicular epithelium. It has been postulated that tretinoin inhibits the synthesis or quality of the substance which binds the horny cells within the sebaceous follicle.
Indications And Clinical Uses: The treatment of acne vulgaris, primarily where comedones, papules and pustules predominate. Tretinoin is not effective in most cases of severe pustular and deep cystic nodular varieties (acne conglobata).
Contra-Indications: Patients with known hypersensitivity to retinoids or to any ingredient contained in the preparation. tag_WarningWarnings
Manufacturers’ Warnings In Clinical States: Tretinoin is intended for external use only and should be kept away from eyes, nose, mouth, and other mucous membranes because of its irritant effect.
Do not apply to eyelids or to the skin at the corners of the eyes and mouth. Avoid the angles of the nose and nasolabial fold (if treatment in these areas is necessary, apply very sparingly). Topical use may induce severe local erythema 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 of eczematous skin and tretinoin should only 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 by used by pregnant women.
There have been rare reports of birth defects among babies born to women exposed to topical tretinoin during pregnancy. However, there are no well controlled prospective studies of the use of topical tretinoin in pregnant women. A retrospective study of mothers exposed to topical tretinoin during the first trimester of pregnancy found no increase in the incidence of birth defects.
Topical retinoid teratology studies in rats and rabbits have been inconclusive. As with all retinoids, tretinoin administered orally at high doses is teratogenic.
Lactation: It is 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.
Precautions: Concomitant topical medications should be used with caution during therapy with tretinoin because of possible intensified reactions. Particular caution should be exercised when using preparations containing a peeling agent concomitantly (such as sulfur, resorcinol, benzoyl peroxide or salicylic acid) with tretinoin. It may be advisable to “rest” a patient’s skin until the effects of previously used peeling agents subside before initiating tretinoin therapy.
Excessive exposure to sunlight or ultraviolet rays (sunlamps) should be avoided during tretinoin treatment, because the additional irradiation may lead to a more intense action.
If a sunburn occurs, it is advisable to interrupt therapy until the severe erythema and peeling subside. Patients whose occupations require considerable exposure to the sun should exercise particular caution.
Adverse Reactions: The skin of certain sensitive individuals, particularly those with fair complexion, may become excessively red, edematous, blistered or crusted when exposed to tretinoin. Pain, burning sensation, tenderness, irritation or pruritus have also been occasionally reported. If any of these effects occur, the medication should be discontinued until the integrity of the skin has been restored or the treatment schedule adjusted to the level the patient can tolerate. Temporary hyper- or hypopigmentation has been reported with repeated application of tretinoin. To date, all adverse clinical effects of tretinoin encountered have been reversible upon discontinuance of therapy. In many instances, reinstitution of therapy with tretinoin failed to produce the adverse effect previously experienced.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Topical: If medication is applied excessively, marked redness, peeling or discomfort may occur.
Dosage And Administration: Tretinoin should be applied to the affected area once a day. The area under treatment (not just clinical lesions) should be thoroughly cleansed with a mild soap, such as Acne-Aid Soap, and dried, followed by application of tretinoin with a gentle rubbing motion. Application may be accompanied by a transitory feeling of warmth or a stinging sensation. Treatment should be discontinued if a severe local inflammatory response is experienced.
In cases where it has been necessary to discontinue therapy or to reduce the frequency of applications, therapy may be resumed, when the adverse effects have ceased. In some patients, during the early weeks of therapy, an apparent exacerbation of the acne lesions may occur.
Therapeutic results may be noticed after 2 to 3 weeks of therapy; however, results may not be optimal until after 8 to 10 weeks of treatment. Once the acne lesions have responded satisfactorily, it may be possible to maintain the improved state with less frequent applications.
Patients being treated with tretinoin may continue to use water-based cosmetics; however, the area of skin to be treated should be thoroughly cleansed and dried before tretinoin application.
Availability And Storage: Each g of cream contains: tretinoin 0.01%, 0.025%, 0.05% or 0.1% in a moisturizing cream base with 7.5% Parsol MCX and 2% Parsol 1789 (SPF 15). Nonmedicinal ingredients: 2-ethyl-hexyl-p-methoxycinnamate, butyl methoxyl dibenzoyl M, butylated hydroxytoluene, carbomer 934 NF, cyclomethicone NF, diisopropyl adipate NF, glycerin USP, imidurea/parabens, isoarachidyl neopentanoate, light mineral oil USP, phenyl timethicone, polysorbate 60 NF, purified water USP, sodium hydroxide 10%, sorbitan monostearate NF and stearyl alcohol NF. Tubes of 25 g. Store between 15 and 30°C.
RETISOL-A® Stiefel Tretinoin Acne Therapy