All-(E)-Retinoic Acid

Uses

• For the treatment of acne vulgaris in which comedones, papules and pustules predominate.
• For the treatment of hyperpigmentation, roughness and fine wrinkling of photodamaged skin due to chronic sun exposure.
• For the treatment of Acute promyelocytic leukaemia

All-(E)-Retinoic Acid is also used to associated treatment for these conditions: Acne Vulgaris, Alopecia, Cornification and dystrophic skin disorders, FAB classification M3 Acute promyelocytic leukemia, Skin hyperpigmentation, Solar Lentigines, Facial fine wrinkling, Keratinization disorders of the feet, Keratinization disorders of the hand, Moderate Melasma, Mottled hyperpigmentation, Severe Melasma, Severe, recalcitrant Cystic acne, Tactile roughness of facial skin

How All-(E)-Retinoic Acid works

All-(E)-Retinoic Acid binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone. Although the exact mechanism of action of tretinoin is unknown, current evidence suggests that the effectiveness of tretinoin in acne is due primarily to its ability to modify abnormal follicular keratinization. Comedones form in follicles with an excess of keratinized epithelial cells. All-(E)-Retinoic Acid promotes detachment of cornified cells and the enhanced shedding of corneocytes from the follicle. By increasing the mitotic activity of follicular epithelia, tretinoin also increases the turnover rate of thin, loosely-adherent corneocytes. Through these actions, the comedo contents are extruded and the formation of the microcomedo, the precursor lesion of acne vulgaris, is reduced. All-(E)-Retinoic Acid is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. When All-(E)-Retinoic Acid is given systemically to APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.

Dosage

All-(E)-Retinoic Acid dosage

All-(E)-Retinoic Acid cream: All-(E)-Retinoic Acid cream should be applied sparingly to the whole affected area once or twice daily. The skin should be thoroughly cleaned and dried before application. Patient should be advised that 6 to 8 weeks of treatment may be required before a therapeutic effect is observed. Moisturisers and cosmetics may be used during treatment with Cosmotrin cream but should not be applied to the skin at the same time. Astringent toiletries should be avoided.

All-(E)-Retinoic Acid gel: All-(E)-Retinoic Acid gel should be applied once or twice a day, before retiring, to the skin where lesions appear, using enough to cover the entire affected area lightly. The frequency of application can be adjusted to obtain maximum clinical efficacy with minimal erythema and scaling.

If All-(E)-Retinoic Acid gel is applied excessively, no more rapid or better results will be obtained and marked redness, peeling or discomfort may occur. Should this occur accidentally or through over-enthusiastic use, application should be discontinued for few days.

Patience is needed in this treatment, since the therapeutic effects will not usually be observed until after 6-8 weeks of treatment. 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 comedones and papules. Once the acne lesions have responded satisfactorily, it should be possible to maintain the improvement with less frequent applications.

Moisturizers and cosmetics may be used during treatment with All-(E)-Retinoic Acid gel but should not be applied to the skin at the same time. The skin should be thoroughly washed before application of All-(E)-Retinoic Acid gel. Astringent toiletries should be avoided.

Capsule: The recommended dose is 45 mg/m2/day administered as two evenly divided doses until complete remission is documented. Therapy should be discontinued 30 days after achievement of complete remission or after 90 days of treatment, whichever occurs first.

If after initiation of treatment of All-(E)-Retinoic Acid the presence of the translocation is not confirmed by cytogenetics and/or by polymerase chain reaction studies and the patient has not responded to All-(E)-Retinoic Acid, alternative therapy appropriate for acute myelogenous leukemia should be considered.

Side Effects

True allergic contact dermatitis is rare but a primary irritant dermatitis, manifesting itself as irritation, erythema, peeling and sensation of warmth, is common. Slight stinging is common as a mild reaction in many people but usually settles with continuous use and/or reduction in the frequency of application of the drug.

Interaction

Particular caution should be exercised in using preparations containing peeling agents (i.e. sulfur, resorcinol, benzoyl peroxide or salicylic acid). Use of topical preparations with high concentrations of alcohol, menthol, spices or lime- such as shaving lotions, astringents and perfume- should be avoided, especially during initial therapy.

Food Interaction

• Take with food. All-(E)-Retinoic Acid absorption may be increased by co-administration with food.

All-(E)-Retinoic Acid Cholesterol interaction

[Moderate] A reversible elevation of cholesterol and

Venous thrombosis and myocardial infarction have occurred in patients at low risk for such complications.

Therapy with tretinoin should be administered cautiously in patients with or predisposed to hypercholesterolemia and

Clinical monitoring of lipid profile is recommended.

All-(E)-Retinoic Acid Drug Interaction

Unknown: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, zolpidem, loratadine, sulfamethoxazole / trimethoprim, ubiquinone, duloxetine, meperidine, venlafaxine, omega-3 polyunsaturated fatty acids, cyclobenzaprine, escitalopram, bifidobacterium infantis / lactobacillus acidophilus, tiotropium, levothyroxine, cyanocobalamin, ascorbic acid, cholecalciferol, lisdexamfetamine

All-(E)-Retinoic Acid Disease Interaction

Major: hepatic dysfunctionModerate: hyperlipidemia

Elimination Route

1-31% (topical)

Half Life

0.5-2 hours

Pregnancy & Breastfeeding use

All-(E)-Retinoic Acid is contraindicated in pregnancy or suspected pregnancy. The drug should be avoided by breast feeding mothers.

Contraindication

All-(E)-Retinoic Acid is contraindicated in patients who are allergic to this drug. It is contraindicated in pregnancy or suspected pregnancy. It is also contraindicated in personal or familial history of cutaneous epithelioma.

Local irritation: The presence of cutaneous irritative signs (e.g. erythema, peeling, pruritus, sunburn, etc.) should prohibit initiation or recommencement of treatment with All-(E)-Retinoic Acid until the symptoms resolve. All-(E)-Retinoic Acid has been reported to cause severe irritation on eczematous skin and should be used with caution in patients with this condition.

Exposure to sunlight: Exposure to sunlight, including ultraviolet sun-lamps, should be avoided or minimised during the use of All-(E)-Retinoic Acid.

General precaution: Before application of All-(E)-Retinoic Acid, areas to be treated should be cleansed thoroughly. Abstain from washing the treated area frequently; twice daily is sufficient. Use of mild soap is recommended. Dry the skin without rubbing.

Avoid contact with eyes, eyelids, nostrils, mouth and mucous membranes. If contact in these areas occurs, careful washing with water is recommended.

Storage Condition

Store in a cool and dry place, away from light. Keep out of reach of children.

Innovators Monograph

You find simplified version here All-(E)-Retinoic Acid