The Retin-A cream and gel label says sunlight exposure should be minimized and that sunscreen and protective clothing are recommended when exposure cannot be avoided. On skin cancer, the authors of a Veterans Affairs randomized trial of 0.1% tretinoin cream concluded that high-dose topical tretinoin is ineffective at reducing risk of keratinocyte carcinomas in high-risk patients. A separate mortality analysis of that trial reported an association with death, and its authors state they do not infer a causal association.
What labels say about sunlight and sunscreen
The Retin-A cream and gel label states that exposure to sunlight, including sunlamps, should be minimized during use, and that patients with sunburn should be advised not to use the product until fully recovered because of heightened susceptibility to sunlight as a result of the use of tretinoin. It says use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. It also says some individuals have been reported to have heightened susceptibility to sunlight while under treatment.
The Renova (tretinoin cream) 0.02% label states that patients should be warned to use sunscreens (minimum SPF of 15) and protective clothing when using the product. It also says the product should not be administered if the patient is also taking drugs known to be photosensitizers (for example thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the possibility of augmented phototoxicity.
The Veterans Affairs trial and keratinocyte carcinoma
In the Veterans Affairs Topical Tretinoin Chemoprevention Trial (J Invest Dermatol, 2012), 1,131 patients were randomized to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years.
The proportions of the tretinoin and control groups who developed a basal cell carcinoma at 5 years were 53 and 54%. The proportions who developed an invasive squamous cell carcinoma at 5 years were 28 and 31%. The authors concluded that this trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of keratinocyte carcinomas.
The separate mortality analysis
An Archives of Dermatology analysis (2009) looked at deaths in the randomized trial, in which tretinoin 0.1% or vehicle cream was applied twice daily to the face and ears per the abstract's methods. It reports that the intervention was terminated 6 months early because of an excessive number of deaths in the tretinoin-treated group.
The same abstract carries the authors' own caveat. They wrote that they observed an association of topical tretinoin therapy with death, but do not infer a causal association that current evidence suggests is unlikely. Both statements come from the same abstract and are reported here as the abstract states them.
Animal data and what a patient-instruction statement says
- Animal data: the Renova 0.02% label says studies in hairless albino mice suggest that concurrent exposure to tretinoin may enhance the tumorigenic potential of carcinogenic doses of UVB and UVA light from a solar simulator. These are animal findings, not human results.
- Label statement: the patient instructions in the Retin-A cream and gel label say there is no evidence to date that tretinoin alone will cause the development of skin tumors in either laboratory animals or humans. This is that label's statement.
- Exclusions: the Renova 0.02% label says patients with visible actinic keratosis and patients with a history of skin cancer were excluded from its clinical trials, and that effectiveness and safety in these populations are not known.
What this does not tell you
The Veterans Affairs results are for 0.1% cream in high-risk patients over 1.5-5.5 years. They are not results for other strengths, and the trial was not an acne or wrinkle trial. The sources used here do not report whether sunscreen use changes skin cancer risk during tretinoin use. The mouse studies are animal data. The two label statements concern different things, and this guide draws no conclusion beyond what each source states.
The labels describe specific products. 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, so none of these findings should be read as a finding for a compounded cream. A licensed provider decides on treatment.