Tretinoin Regulatory Status: US, EU, Canada, and UK Explained

What is Renova 0.02% cream approved for in the US?

Renova (tretinoin cream) 0.02% is indicated as an adjunctive agent for use in the mitigation (palliation) of fine facial wrinkles in patients who use comprehensive skin care and sunlight avoidance programs [1]. The label limits that claim: it does not eliminate wrinkles, repair sun-damaged skin, reverse photoaging or restore a more youthful skin structure [1]. It has not demonstrated a mitigating effect on coarse or deep wrinkling, tactile roughness, mottled hyperpigmentation, lentigines, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia or dermal elastosis [1].

The label also states that neither the safety nor the efficacy of daily use beyond 52 weeks has been established, and that neither the safety nor the effectiveness for preventing or treating actinic keratoses or skin neoplasms has been established [1].

The label describes five trials with a total of 324 evaluable patients on Renova 0.02% and 332 on vehicle cream, treated on the face for 24 weeks with a comprehensive skin care and sun avoidance program [1]. Two of the five trials adequately demonstrated efficacy for mitigation of fine facial wrinkling; none of the trials adequately demonstrated efficacy for coarse wrinkling, mottled hyperpigmentation, tactile skin roughness or laxity [1]. In one single-center study of 107 darkly pigmented patients, 43% of vehicle users and 29% of Renova users showed minimal or mild improvement in fine facial wrinkling, which the label notes may reflect the small size of that study [1].

Does the Renova label carry a boxed warning?

No. The Renova 0.02% cream label does not contain a boxed warning. Its warnings cover local irritation, photosensitivity and sun exposure [1].

The label calls Renova a dermal irritant and says the results of continued irritation beyond 52 weeks are not known [1]. It says exposure to sunlight, including sunlamps, should be avoided or minimized because of heightened sunburn susceptibility, advises sunscreens with a minimum SPF of 15 and protective clothing, and says patients with sunburn should not use the cream until fully recovered [1]. The label also says Renova should not be used by patients taking drugs known to be photosensitizers, such as thiazides, tetracyclines, fluoroquinolones, phenothiazines or sulfonamides, because of possible augmented phototoxicity [1].

Local reactions are common. In double-blind vehicle-controlled studies of 339 patients applying Renova 0.02% to the face, almost all reported one or more local reactions such as peeling, dry skin, burning, stinging, erythema and pruritus, and 32% had skin irritation that was severe, led to temporary discontinuation or required a mild topical corticosteroid [1]. About 4% discontinued because of adverse reactions [1].

What does the label say about pregnancy?

The dosage and administration section says not to use Renova 0.02% if the patient is pregnant, attempting to become pregnant or at high risk of pregnancy [1]. The teratogenic effects section reports that oral tretinoin is teratogenic in animals and that topical animal results are equivocal. It also reports 30 human cases of temporally associated congenital malformations during two decades of clinical use of another topical tretinoin formulation, including five holoprosencephaly reports, with no definite pattern of teratogenicity and no causal association established [1].

Is compounded tretinoin FDA-approved?

No. Compounded drugs are not FDA-approved, and the FDA does not verify their safety, effectiveness or quality before they are marketed [2]. The FDA states that compounded drugs should be used only in patients whose medical needs cannot be met by an FDA-approved drug, and that unnecessary use may expose patients to serious risks, including contamination or a drug that contains too much or too little active ingredient [2].

Is tretinoin prescription-only in the EU, UK and Canada?

This page does not cover EU, UK or Canadian classification, approved indications or concentrations. The prescription status and the wrinkle indication described above are the US position for Renova 0.02% cream [1].