Labels, trials and reviews report skin irritation with topical tretinoin products. The Renova (tretinoin cream) 0.02% label says almost all patients reported one or more local reactions such as peeling, dry skin, burning, stinging, erythema, and pruritus. The percentages below come from labels and studies of other products. They are not rates for compounded creams.
What labels warn about
- The Retin-A cream and gel label says topical use may induce severe local erythema and peeling at the site of application. It says patients should be directed to use the medication less frequently, discontinue use temporarily, or discontinue use altogether if the degree of local irritation warrants.
- The same label says the skin of certain sensitive individuals may become excessively red, edematous, blistered, or crusted, and that temporary hyper- or hypopigmentation has been reported with repeated application. Its patient instructions say that if you are experiencing severe or persistent irritation, discontinue the use of Retin-A and consult your physician.
- The Renova 0.02% label calls it a dermal irritant and says the results of continued irritation of the skin for greater than 52 weeks in chronic use are not known. It says there is evidence of atypical changes in melanocytes and keratinocytes and of increased dermal elastosis in some patients treated with Renova 0.05% for longer than 48 weeks. The passage does not say what those changes mean for health.
- A generic tretinoin cream 0.05% label for acne says to keep it away from the eyes, the mouth, angles of the nose, and mucous membranes, and to use caution with preparations containing sulfur, resorcinol, or salicylic acid, with medicated or abrasive soaps and cleansers, and with soaps and cosmetics that have a strong drying effect.
- The Twyneo label, for a cream that combines tretinoin and benzoyl peroxide, says in its patient information to stop using Twyneo and get medical help right away if you have hives, rash or severe itching, or swelling of your face, eyes, lips, tongue, or throat.
Rates reported on labels of other products
| Question | What the source says |
|---|---|
| Renova (tretinoin cream) 0.02%: double-blind, vehicle-controlled studies in 339 patients who applied it to their faces (study length not given in the passage): what was reported? | In 32% of all study patients, skin irritation was reported that was severe, led to temporary discontinuation, or led to use of a mild topical corticosteroid. About 7% of patients using it, compared to less than 1% of control patients, had local irritation severe enough to warrant short-term use of mild topical corticosteroids. |
| Retin-A Micro (tretinoin) 0.1% gel microsphere, 12-week treatment period: what was reported? | No more than 3% of treated subjects had cutaneous irritation scores indicative of severe cutaneous irritation, and 6% (14/224) discontinued treatment due to cutaneous irritation. |
| Atralin (tretinoin) gel 0.05%: Atralin Gel (N = 674) versus vehicle (N = 487), study length not given in the passage: what was reported? | Selected adverse reactions: dry skin 109 (16%) versus 8 (2%); peeling/scaling/flaking skin 78 (12%) versus 7 (1%); skin burning sensation 53 (8%) versus 8 (2%); erythema 47 (7%) for Atralin Gel, with no vehicle figure in the passage. |
What trials and reviews report
In the Veterans Affairs Topical Tretinoin Chemoprevention Trial, participants used 0.1% cream or vehicle control cream once daily, then twice daily as tolerated, and were told to step down to once daily or less if twice daily was not tolerated. At the 6-month follow-up, the tretinoin group more commonly reported one or more side-effects than the control group (61% vs. 42%). Burning was the most common side-effect (39% tretinoin vs. 17% control). The tretinoin group was less likely to apply cream twice daily at 6 months (29% vs. 43%).
A 1995 trial in photoaging patients comparing 0.1% and 0.025% creams reported a significantly greater incidence of irritation with the higher concentration. A systematic review of topical retinoids in acne reported that tretinoin 0.05% resulted in 62% of patients experiencing adverse events, compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). A 2022 systematic review and network meta-analysis of acne treatments states that BPO and topical retinoids were less well tolerated than placebo.
A 2006 trial in people using oral isotretinoin or topical tretinoin (tretinoin strength not stated) concluded that retinoid-induced skin irritation can be relieved by regular use of a gentle moisturizing cream as an adjunctive treatment. That sentence covers both oral isotretinoin and topical tretinoin, and this guide is about topical tretinoin only. A systematic review of acne treatment adherence reported that reasons for nonadherence included cost, side effects, perceived treatment ineffectiveness or symptom resolution.
What this does not tell you
The percentages come from different products, formulations (cream and gel), vehicles, study lengths and groups of people, so they should not be compared. The FDA states that compounded drugs are not FDA-approved, meaning FDA does not verify the safety, effectiveness or quality of compounded drugs before they are marketed.
These sources describe groups, not any one person's risk. This guide does not advise starting, stopping or changing a product or strength. A licensed provider decides that.