Brand names: Avita, Renova Emollient, Retin-A, Retin-A Micro
Drug class: Cell Stimulants and Proliferants
VA class: DE752
CAS number: 302-79-4

Introduction

All trans-retinoic acid; a retinoid.

Uses for Tretinoin (Topical)

Acne

Treatment of acne vulgaris, principally grades I–III, in which comedones, papules, and pustules predominate.

Generally not effective for treatment of severe pustular and deep nodulocystic acne; however, may be used as adjunctive therapy in the management of associated comedones.

Photoaging

Palliative therapy to improve dermatologic changes (e.g., fine wrinkling, mottled hyperpigmentation, roughness) associated with photodamage.

Use as an adjunct to a comprehensive skin care plan and sun avoidance program; reserve use for patients who do not achieve the desired effects with such programs alone (i.e., without tretinoin).

Safety and efficacy not established in individuals with moderately or highly pigmented skin or patients with actinic keratoses or a history of skin cancer.

Tretinoin (Topical) Dosage and Administration

General

• Excessive use does not increase therapeutic effects and may produce marked inflammatory reactions (e.g., erythema, peeling, discomfort). (See Dermatologic Effects under Cautions.)

• Use of moisturizers concomitantly at night may dilute the therapeutic effect of the drug; if required, moisturizers should be used during the day.

Administration

Topical Administration

Apply topically to the skin as a cream, gel, or solution.

Gently wash skin with mild soap, pat dry, and wait 20–30 minutes before applying tretinoin to affected areas; avoid the eyes, ears, nostrils, mucous membranes, and mouth.

A transient feeling of warmth or minor stinging may occur immediately after application.

If therapy is not well tolerated, temporarily discontinue or decrease frequency of applications; reinitiate therapy when patient is able to tolerate the drug. Closely monitor patient response and tolerance to changes in dosage form, drug concentration, or application frequency.

Acne

Apply a sufficient amount of cream, gel, or solution to cover affected area lightly.

Apply cream or gel using clean fingertips.

Apply solution using clean fingertips, gauze pad, or cotton swab; avoid oversaturation of gauze or cotton so solution will not run onto unaffected areas.

Excessive application of gel results in “pilling” or “caking,” which minimizes overapplication.

Photoaging

Apply 0.02 or 0.05% cream topically to face using a clean fingertip; apply a sufficient amount to cover entire face lightly.

Gently wash treated skin with fingertips to peel away loose outer layers of the skin that may form during therapy. Erosion may occur if patients are not careful with scale removal.

Dosage

Pediatric Patients

Acne

Topical

Adolescents ≥12 years of age: Apply once daily at bedtime.

Because of potential to cause severe irritation and peeling, therapy can be initiated using a lower concentration cream or gel applied every 2 or 3 days at bedtime; if tolerated, solution or higher concentration cream or gel can be used.

Initial response (redness, scaling, and possibly more pronounced comedones) occurs within 7–10 days. Therapeutic effects usually are apparent after 2–3 weeks; optimal effects may require >6 weeks of therapy.

Relapses generally occur within 3–6 weeks after therapy is discontinued.

Adults

Acne

Topical

Apply once daily at bedtime.

Because of potential to cause severe irritation and peeling, therapy can be initiated using a lower concentration cream or gel applied every 2 or 3 days at bedtime; if tolerated, solution or higher concentration cream or gel can be used.

Initial response (redness, scaling, and possibly more pronounced comedones) occurs within 7–10 days. Therapeutic effects usually are apparent after 2–3 weeks; optimal effects may require >6 weeks of therapy.

Relapses generally occur within 3–6 weeks after therapy is discontinued.

Photoaging

Topical

Apply a pea-sized amount of the 0.02 or 0.05% cream once daily at bedtime.

Individualize dosage according to patient response and tolerance, depending on skin type, degree of photoaging present, race, and/or age of the patient. Mild scaling can be used as a guide in determining tolerance level.

If therapy is not well tolerated, may reduce frequency to every other night or every third night.

Maintenance regimen of 2–4 applications weekly suggested for some patients once maximum response has been achieved.

Therapeutic response occurs gradually over 6 months; clinically important decreases in fine wrinkles may not be apparent for 8 weeks.

Therapeutic effects may be lost when therapy and accompanying comprehensive skin care and sun avoidance are discontinued.

Prescribing Limits

Adults

Photoaging

Topical

Safety and efficacy of therapy with 0.02% cream for >52 weeks or with 0.05% cream for >48 weeks not established.

Cautions for Tretinoin (Topical)

Contraindications

• Known hypersensitivity to tretinoin or any ingredient in the formulation.

Warnings/Precautions

Warnings

Gel Formulations

Gels are flammable; avoid heat, flames, or smoking during use of gel formulations (Retin-A, Avita).

Dermatologic Effects

Possible severe erythema, edema, blistering, or crusting of the skin. If severe reaction occurs, use less frequently, discontinue until skin integrity is restored, or permanently discontinue, depending on the severity of the reaction.

Avoid contact of drug with the eyes, mouth, angles of the nose, mucous membranes, or open wounds.

Atypical changes in melanocytes and keratinocytes and increased dermal elastosis reported with use of 0.05% cream for >48 weeks; clinical importance is unknown.

Exposure to Utraviolet (UV) Light

Exposure to UV light increases the intensity of the inflammatory reaction to tretinoin therapy. (See Photosensitivity under Cautions.)

Tretinoin, especially at high concentrations, may increase the tumorigenic potential of UV radiation.

Eczema

Possible severe irritation of eczematous skin. Use with extreme caution in patients with eczema.

Sensitivity Reactions

Photosensitivity

Increased risk for sunburn.

Cautious use recommended in patients subjected to considerable occupational sun exposure and those with inherent sensitivity to the sun; use of sunscreen products (SPF 15 or greater) and protective clothing over treated areas recommended when exposure cannot be avoided.

Avoid concomitant use of photosensitizing agents . (see Specific Drugs under Interactions)

Use not recommended for patients with sunburn until full recovery occurs.

Minimize exposure to sunlight and avoid use of sunlamps.

Other Sensitivity Reactions

Contact allergy occurs rarely.

Discontinue therapy if sensitivity reaction, chemical irritation, or systemic adverse reaction occurs.

General Precautions

Environmental Stimuli

Possible increased skin irritation in patients exposed to environmental extremes (e.g., wind, cold) and other stimuli (e.g., excessive heat, diaphoresis, increased skin contact with jewelry, concomitant use of irritating cosmetics or facial saunas).

Dry Skin

Possible excessive dry skin in patients receiving gel formulation for acne; an appropriate emollient may be used during the day.

Moisturizers (used at least every morning) are recommended as part of a comprehensive skin care plan for individuals with photoaging.

Facial Cleansing

Use of mild, bland soap not more than 2 or 3 times daily is recommended; use of medicated or drying soaps and abrasive soaps and cleansers generally should be avoided.

Cosmetic Agents or Processes

Avoid use of irritating cosmetics and other preparations or processes (e.g., electrolysis) that might dry or irritate the skin. (See Other Topical Preparations under Interactions.) Medicated cosmetics are not recommended.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether topical tretinoin is distributed into milk. Caution advised if topical tretinoin is used.

Pediatric Use

Safety and efficacy not established for treatment of acne in children <12 years of age (Retin-A Micro) or for treatment of photoaging in children <18 years of age (Renova).

Geriatric Use

Safety and efficacy of emollient cream formulation (Renova 0.05%) or cream formulation (Renova 0.02%) for treatment of photoaging not etablished in adults ≥51 or ≥72 years of age, respectively.

Insufficient experience in patients ≥65 years of age to determine whether safety and efficacy of gel formulation (Retin-A, Retin-A Micro) for treatment of acne in geriatric patients differ from safety and efficacy in younger adults.

Common Adverse Effects

Transitory feeling of warmth or slight stinging, redness and scaling of the skin, peeling, dry skin, burning, pruritus.

Drug Interactions

Specific Drugs

Other Topical Preparations

Potential pharmacodynamic interaction (increased skin irritation). To the extent possible, avoid concurrent use of topical preparations with high concentrations of alcohol, menthol, spices, or lime (e.g., lotions, astringents, perfume); irritating cosmetics (e.g., toners, peeling [desquamating] agents); permanent wave solutions; electrolysis; or hair depilatories or waxes.

Tretinoin (Topical) Pharmacokinetics

Absorption

Bioavailability

Minimally absorbed following topical application.

Stability

Storage

Topical

Cream, Gel, or Solution

Tight, light-resistant containers at 15–30°C; do not freeze.

Do not expose gel formulations (Retin-A, Avita) to heat or flame.

Actions

• Precise mechanism of action for treatment of acne not determined. May inhibit keratinization, irritate the follicular epithelium (preventing horny cells from sticking together), or incite inflammatory reactions (resulting in acanthosis and parakeratosis).

• Increases horny cell production in existing comedones and causes formation of an intrafollicular abscess, resulting in suppurative discharge of comedones. Inhibits formation of additional comedones by expelling horny cells from the follicular orifice.

• Modulates proliferation and differentiation of epidermal cells via activation of nuclear retinoic acid receptors, which causes change in gene expression; relationship to regulation of skin function not understood.

• Partially reverses photodamaged skin histologically and clinically. Use associated with restoration of epidermis to a normal morphologic appearance and increased epidermal thickness; reduction or eradication of microscopic actinic keratoses; dispersion of melanin granules and decreased melanin content; stratum corneum compaction; new collagen formation in the papillary dermis; increased epidermal-dermal anchoring fibrils; angiogenesis; exfoliation of retained follicular horn; reduction of fine wrinkling and, to a lesser degree, coarse wrinkling and tactile roughness of the skin; and increased skin pinkness.

• May reduce collagen degradation by inducing tissue inhibitors of collagenase.

• Importance of advising patients that topical tretinoin is not a cosmetic preparation.

• Importance of clinicians instructing patients about proper use of the drug, including associated precautions. Provide copy of the manufacturer’s patient instructions.

• Importance of avoiding use of shaving lotions, astringents, perfumes, toners, peeling [desquamating] agents, permanent wave solutions, electrolysis, hair depilatories or waxes, medicated cosmetics, or other products that may irritate the skin.

• Importance of avoiding excessive use of topical tretinoin. Importance of temporarily discontinuing therapy or decreasing frequency of application if therapy is not well tolerated.

• Risk of photosensitivity reaction; importance of using sunscreen products and wearing protective clothing over treated areas.

• Importance of using moisturizers, if required (e.g., in patients with photoaging, to relieve dryness associated with tretinoin preparation), only during the day.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of avoiding heat, flames, or smoking during use of gel formulations (Retin-A, Avita).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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