STIEVAMYCIN® Preparations Stiefel Erythromycin–Tretinoin Topical Acne Therapy
Action and Clinical
Tretinoin: 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 two 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.
Erythromycin: Erythromycin exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible bacteria and suppressing protein synthesis. Erythromycin is usually bacteriostatic but may be bactericidal in high concentrations or against highly susceptible organisms.
The precise mechanism of action of erythromycin in the treatment of acne has not been established.
Indications And Clinical Uses:
In the treatment of acne vulgaris, primarily where comedones, papules and pustules predominate. Not effective in most cases of severe pustular and deep cystic nodular varieties (acne conglobata). Not indicated in Stage IV acne.
In patients with known hypersensitivity to retinoids and/or erythromycin or any of the components of the preparations.
Warnings in Clinical States:
Topical gels are 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 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 be 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.
The safety of erythromycin during pregnancy has not been established. Erythromycin crosses the placental barrier.
Lactation: It is unknown whether tretinoin is excreted in human milk but erythromycin is so excreted. 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.
The use of preparations containing antibiotics may be associated with overgrowth of antibiotic resistant organisms, including those initially sensitive to the drug. Cross-resistance between erythromycin and macrolide antibiotics can occur. If this should occur, therapy should be discontinued and appropriate measures taken. A cross-resistance between erythromycin and clindamycin has rarely been reported.:
Excessive exposure to sunlight or ultraviolet rays (sun lamps) should be avoided during treatment with Stievamycin topical gels 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.
Concomitant topical medications should be used with caution during therapy with Stievamycin topical gels 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 Stievamycin. It may be advisable to “rest” a patient’s skin until the effects of previously used peeling agents subside before initiating Stievamycin therapy. Concurrent use of abrasive or medicated soaps, or cosmetic products containing alcohol, such as astringents and after-shave lotions, may also result in a cumulative drying or irritant effect in patients using Stievamycin topical gels.
The skin of certain sensitive individuals, particularly those with fair complexion, may become excessively red, edematous, blistered or crusted when exposed to Stievamycin topical gels. 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.
Topical erythromycin may cause desquamation and excessive dryness. Mild to moderate irritation has been observed in many patients, but severe irritation is generally less frequent. Urticaria, oiliness, coriaceousness and fissuring around the mouth may occur.
Symptoms And Treatment Of Overdose:
Topical: If medication is applied excessively, marked redness, peeling or discomfort may occur.
Accidental Ingestion: In oral doses of over 2Â g erythromycin per day, abdominal discomfort, nausea or diarrhea may occur. There is no specific treatment. Gastric lavage should be considered, otherwise, the treatment should be symptomatic.
Dosage And Administration:
Stievamycin topical gels should be applied to the affected area once a day, preferably before retiring. The area under treatment (not just clinical lesions) should be thoroughly cleansed with a mild soap, and dried, followed by application of the gel in a gentle rubbing motion, using fingertips to apply medication. 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 may be necessary to discontinue therapy or 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 Stievamycin topical gels may continue to use cosmetics; however, astringents may produce exacerbation when used concurrently with Stievamycin topical gels. The area of skin to be treated should be thoroughly cleansed and dried before Stievamycin topical gels are applied.
Availability And Storage:
Forte: Each g of gel contains: tretinoin USP 0.05% and erythromycin USP 4.0% in an alcohol gel base. Nonmedicinal ingredients: BHT, ethyl alcohol and hydroxypropyl cellulose. Tubes of 25 g.
Mild: Each g of gel contains: tretinoin USP 0.01% and erythromycin USP 4.0% in an alcohol gel base. Nonmedicinal ingredients: BHT, ethyl alcohol and hydroxypropyl cellulose. Tubes of 25 g.
Regular: Each g of gel contains: tretinoin USP 0.025% and erythromycin USP 4.0% in an alcohol gel base. Nonmedicinal ingredients: BHT, ethyl alcohol and hydroxypropyl cellulose. Tubes of 25 g.
Store between 15 and 30°C.
STIEVAMYCIN® Preparations Stiefel Erythromycin–Tretinoin Topical Acne Therapy