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Tretinoin topical

Class: Cell Stimulants and Proliferants
VA Class: DE752
CAS Number: 302-79-4
Brands: Avita, Renova Emollient, Retin-A, Retin-A Micro

Medically reviewed by Last updated on May 22, 2020.


All trans-retinoic acid; a retinoid.128

Uses for Tretinoin


Treatment of acne vulgaris,134 135 137 c principally grades I–III, in which comedones, papules, and pustules predominate.b

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.b


Palliative therapy to improve dermatologic changes (e.g., fine wrinkling, mottled hyperpigmentation, roughness) associated with photodamage.104 105 112 113 114 115 116 117 120 122 126 128 129 136

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).128

Safety and efficacy not established in individuals with moderately or highly pigmented skin or patients with actinic keratoses or a history of skin cancer.128 136

Tretinoin Dosage and Administration


  • Excessive use does not increase therapeutic effects and may produce marked inflammatory reactions (e.g., erythema, peeling, discomfort).128 135 136 b c (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.104 124 125 126


Topical Administration

Apply topically to the skin as a cream, gel, or solution.128 134 135 136 137 c

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.115 117 121 123 124 126 128 129 136 c

A transient feeling of warmth or minor stinging may occur immediately after application.128 134 135 136 137 c

If therapy is not well tolerated, temporarily discontinue or decrease frequency of applications;105 113 122 123 124 125 126 c reinitiate therapy when patient is able to tolerate the drug.115 122 123 124 125 136 c Closely monitor patient response and tolerance to changes in dosage form, drug concentration, or application frequency.125 135


Apply a sufficient amount of cream, gel, or solution to cover affected area lightly.134 135 137 c

Apply cream or gel using clean fingertips.134 c

Apply solution using clean fingertips, gauze pad, or cotton swab;137 avoid oversaturation of gauze or cotton so solution will not run onto unaffected areas.137

Excessive application of gel results in “pilling” or “caking,” which minimizes overapplication.135 137


Apply 0.02 or 0.05% cream topically to face using a clean fingertip;115 117 121 123 124 126 128 129 136 apply a sufficient amount to cover entire face lightly.128 136

Gently wash treated skin with fingertips to peel away loose outer layers of the skin that may form during therapy.b Erosion may occur if patients are not careful with scale removal.129


Pediatric Patients


Adolescents ≥12 years of age: Apply once daily at bedtime.135 137 c d e

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.b

Initial response (redness, scaling, and possibly more pronounced comedones) occurs within 7–10 days.135 137 b c Therapeutic effects usually are apparent after 2–3 weeks; optimal effects may require >6 weeks of therapy.137 c

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



Apply once daily at bedtime.135 137 c

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.b

Initial response (redness, scaling, and possibly more pronounced comedones) occurs within 7–10 days.135 137 b c Therapeutic effects usually are apparent after 2–3 weeks; optimal effects may require >6 weeks of therapy.137 c

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


Apply a pea-sized amount of the 0.02 or 0.05% cream104 113 114 122 126 128 136 once daily at bedtime.128 136

Individualize dosage according to patient response and tolerance, depending on skin type, degree of photoaging present, race, and/or age of the patient.115 121 124 125 Mild scaling can be used as a guide in determining tolerance level.115 124

If therapy is not well tolerated, may reduce frequency to every other night or every third night.105 113 122 123 124 125 126

Maintenance regimen of 2–4 applications weekly suggested for some patients once maximum response has been achieved.115 123 124 125 126

Therapeutic response occurs gradually over 6 months; clinically important decreases in fine wrinkles may not be apparent for 8 weeks.105 121 123 129 136

Therapeutic effects may be lost when therapy and accompanying comprehensive skin care and sun avoidance are discontinued.136

Prescribing Limits



Safety and efficacy of therapy with 0.02% cream for >52 weeks128 or with 0.05% cream for >48 weeks not established.136

Cautions for Tretinoin


  • Known hypersensitivity to tretinoin or any ingredient in the formulation.128 135 c



Gel Formulations

Gels are flammable;137 c avoid heat, flames, or smoking during use of gel formulations (Retin-A, Avita).a

Dermatologic Effects

Possible severe erythema, edema, blistering, or crusting of the skin.128 135 137 c If severe reaction occurs, use less frequently, discontinue until skin integrity is restored, or permanently discontinue, depending on the severity of the reaction.128 135 137 c

Avoid contact of drug with the eyes, mouth, angles of the nose, mucous membranes, or open wounds.128 135 137 c

Atypical changes in melanocytes and keratinocytes and increased dermal elastosis reported with use of 0.05% cream for >48 weeks; clinical importance is unknown.136

Exposure to Utraviolet (UV) Light

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

Tretinoin, especially at high concentrations, may increase the tumorigenic potential of UV radiation.128 b


Possible severe irritation of eczematous skin.128 135 137 c Use with extreme caution in patients with eczema.128 135 137 c

Sensitivity Reactions


Increased risk for sunburn.104 105 115 123 124 125 126 128 129 c

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)128 135 136 137 c and protective clothing over treated areas recommended when exposure cannot be avoided.128 134 135 136 137 c

Avoid concomitant use of photosensitizing agents .128 136 (see Specific Drugs under Interactions)

Use not recommended for patients with sunburn until full recovery occurs.128 135 137 c

Minimize exposure to sunlight and avoid use of sunlamps.128 134 135 137 c

Other Sensitivity Reactions

Contact allergy occurs rarely.137 c

Discontinue therapy if sensitivity reaction, chemical irritation, or systemic adverse reaction occurs.128 134 135 136 137 c

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).104 105 115 123 124 125 126 128 129 137 c

Dry Skin

Possible excessive dry skin in patients receiving gel formulation for acne; an appropriate emollient may be used during the day.135

Moisturizers (used at least every morning) are recommended as part of a comprehensive skin care plan for individuals with photoaging.128 136

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.128 135 136 c

Cosmetic Agents or Processes

Avoid use of irritating cosmetics and other preparations or processes (e.g., electrolysis) that might dry or irritate the skin.128 135 136 137 c (See Other Topical Preparations under Interactions.) Medicated cosmetics are not recommended.b

Specific Populations


Category C.128 135 c


Not known whether topical tretinoin is distributed into milk.134 135 136 137 Caution advised if topical tretinoin is used.134 135 136 137

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).128 135 136

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.128 136

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.135 a

Common Adverse Effects

Transitory feeling of warmth or slight stinging, redness and scaling of the skin, peeling, dry skin, burning, pruritus.128 135 136 b

Interactions for Tretinoin

Specific Drugs




Keratolytic agents (e.g., sulfur, resorcinol, benzoyl peroxide, salicylic acid)

Possible additive effects135 137 c

Allow sufficient time for the effects of the keratolytic agent to subside before initiating tretinoin therapy135 137 c

Photosensitizing agents (e.g., fluoroquinolone anti-infectives, thiazide diuretics, sulfonamides, tetracyclines, phenothiazines)

Possible increased phototoxicity128 136

Avoid concomitant use128 136

Other Topical Preparations

Potential pharmacodynamic interaction (increased skin irritation).115 124 125 126 127 128 135 136 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.115 124 125 126 127 128 135 136

Tretinoin Pharmacokinetics



Minimally absorbed following topical application.128 134 135 b c




Cream, Gel, or Solution

Tight, light-resistant containers at 15–30°C;b do not freeze.134 136 c

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


  • Precise mechanism of action for treatment of acne not determined.b May inhibit keratinization,b irritate the follicular epithelium (preventing horny cells from sticking together),135 b c or incite inflammatory reactions (resulting in acanthosis and parakeratosis).b

  • Increases horny cell production in existing comedones and causes formation of an intrafollicular abscess, resulting in suppurative discharge of comedones.135 b c Inhibits formation of additional comedones by expelling horny cells from the follicular orifice.135 b c

  • 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.135

  • Partially reverses photodamaged skin histologically and clinically.104 105 112 113 115 116 121 122 123 124 125 126 129 Use associated with restoration of epidermis to a normal morphologic appearance and increased epidermal thickness;104 105 113 114 117 123 124 125 126 129 reduction or eradication of microscopic actinic keratoses;104 105 124 dispersion of melanin granules and decreased melanin content;104 113 114 123 124 125 126 129 stratum corneum compaction;104 105 113 117 126 new collagen formation in the papillary dermis;104 116 123 124 125 129 increased epidermal-dermal anchoring fibrils;112 114 116 126 129 angiogenesis;104 123 124 125 exfoliation of retained follicular horn;104 126 reduction of fine wrinkling and, to a lesser degree, coarse wrinkling and tactile roughness of the skin; and increased skin pinkness.104 105 112 113 115 116 121 122 123 124 125 126 129

  • May reduce collagen degradation by inducing tissue inhibitors of collagenase.112 116 118 119

Advice to Patients

  • Importance of advising patients that topical tretinoin is not a cosmetic preparation.128

  • Importance of clinicians instructing patients about proper use of the drug, including associated precautions.128 Provide copy of the manufacturer’s patient instructions.128

  • 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.115 124 125 126 127 128 136 135

  • Importance of avoiding excessive use of topical tretinoin.128 135 136 b c Importance of temporarily discontinuing therapy or decreasing frequency of application if therapy is not well tolerated.105 113 122 123 124 125 126

  • Risk of photosensitivity reaction; importance of using sunscreen products and wearing protective clothing over treated areas.104 105 115 123 124 125 126 128 129

  • Importance of using moisturizers, if required (e.g., in patients with photoaging, to relieve dryness associated with tretinoin preparation), only during the day.104 124 125 126

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.128 135 c

  • Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.128 135 c

  • Importance of avoiding heat, flames, or smoking during use of gel formulations (Retin-A, Avita).135 a

  • Importance of informing patients of other important precautionary information.128 135 c (See Cautions.)


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



Dosage Forms


Brand Names





Renova Emollient (with methylparaben)




Mylan Bertek




Renova Emollient (with methylparaben)









Retin-A (with denatured alcohol 90% and butylated hydroxytoluene)




Mylan Bertek

Retin-A (with denatured alcohol 90% and butylated hydroxytoluene)


Gel (containing microspheres)


Retin-A Micro (with benzyl alcohol and propylene glycol)



Retin-A Micro (with benzyl alcohol and propylene glycol)




Retin-A (with denatured alcohol 55%, butylated hydroxytoluene, and polyethylene glycol 400)


AHFS DI Essentials™. © Copyright 2020, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


Only references cited for selected revisions after 1984 are available electronically.

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102. Kligman LH. Effects of all-trans-retinoic acid on the dermis of hairless mice. J Am Acad Dermatol. 1986; 15(4 Part 2):779-85,884-7.

103. Anon. Ortho testing antiaging use of acne remedy. Med Advert News. 1986; 5(Oct 1):1.

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