Tretinoin and Rosuvastatin Interaction: Safety, Risks, and What Your Doctor Should Know

The Short Answer

The labels do not list an interaction between the two. Tretinoin is not among the drugs the Crestor label lists in its dose-modification table for interacting medicines [1], and the Renova 0.02% cream label's drug interactions section does not name rosuvastatin [2].

Not being listed is not the same as being shown safe. The useful review is each drug's documented risks, plus the one fact that would matter most for a systemic interaction: how much tretinoin actually reaches the bloodstream.

Tretinoin is a retinoid, a metabolite of vitamin A that binds retinoic acid receptors in the skin [2]. Rosuvastatin is an HMG-CoA reductase inhibitor, or statin, taken by mouth [1].

What the Tretinoin Label Says About Absorption and Interactions

The tretinoin information here comes from the Renova 0.02% cream label, so it covers that one cream rather than every tretinoin gel or cream [2].

The Renova label warns that skin-irritating products used at the same time may increase irritation: concomitant topical medications, medicated or abrasive soaps, shampoos, cleansers, strongly drying cosmetics, products with high concentrations of alcohol, astringents, spices or lime, permanent wave solutions, electrolysis, hair depilatories or waxes [2]. It also says the cream should not be administered with drugs known to be photosensitizers — thiazides, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides — because of possible augmented phototoxicity [2].

Absorption is not zero. The same label reports that transdermal absorption of tretinoin from various topical formulations ranged from 1% to 31% of the applied dose, depending on whether it was applied to healthy skin or dermatitic skin [2]. In a study described in the label, a 0.05% cream in seven healthy men was absorbed less than 2% after a single application and after 28 days of daily application, and bioavailability was lower after repeated use [2]. No percutaneous absorption study was conducted with Renova 0.02% itself [2].

So some of what is applied can enter the circulation, and how much depends on the product and the state of the skin.

What the Crestor Label Lists as Interactions

Crestor is taken at 5 to 40 mg once daily, at any time of day, with or without food [1]. Its dose-modification table gives limits or avoidance advice for a specific list of medicines: with cyclosporine, do not exceed 5 mg daily; with gemfibrozil, avoid the combination, or if unavoidable start at 5 mg and do not exceed 10 mg daily; and a longer list of antivirals and other drugs — including belumosudil, darolutamide, tafamidis and ticagrelor — carries dose caps or avoidance advice of its own [1]. Tretinoin is not among them [1].

The size of the two best-characterized effects: cyclosporine raised rosuvastatin AUC 7.1-fold and peak concentration 10.6-fold in 10 heart transplant recipients compared with historical healthy controls [1][3], and gemfibrozil raised AUC 1.88-fold and peak concentration 2.21-fold after a single 80 mg rosuvastatin dose in a randomized crossover trial of 20 healthy volunteers [4]. Those are dose limits and cautions, not contraindications; the label's contraindications are acute liver failure, decompensated cirrhosis and hypersensitivity to rosuvastatin or its excipients [1].

Separately from that table, the label says to take Crestor at least 2 hours before an aluminum/magnesium hydroxide antacid; taken at the same time, the antacid cut rosuvastatin exposure by about half [1]. It also says rosuvastatin significantly increased the INR in patients on warfarin, and asks for INR checks before starting and often enough after starting, titration or stopping [1]. The label says rosuvastatin clearance does not depend on CYP3A4 to a clinically significant extent (itraconazole raised exposure only about 1.4-fold), and names transporter inhibitors such as cyclosporine, certain HIV protease inhibitors and ticagrelor as the interactions that matter [1].

Oral Isotretinoin Is Different From Topical Tretinoin

Isotretinoin is an oral retinoid given for severe acne; topical tretinoin is applied to the skin. The lipid findings described here concern oral isotretinoin. In a 1985 study of 60 patients treated with oral isotretinoin for nodulocystic acne over 20 weeks, maximum mean triglyceride increases were 46.3 mg/dL in men and 52.3 mg/dL in women, and 9 of the 53 patients (17%) who completed 20 weeks developed triglyceride levels of 200 to 600 mg/dL; cholesterol and LDL cholesterol rose, HDL cholesterol fell, and levels returned to baseline by eight weeks after the drug was stopped [5].

The Renova 0.02% cream label's adverse reactions are local skin reactions; it does not report lipid changes [2].

What to Watch For on Each Drug

For the cream, the labeled effects are at the application site. 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 itching; in 32% the irritation was severe, led to temporary discontinuation, or led to use of a mild topical corticosteroid, and about 4% discontinued because of adverse reactions [2].

Sun exposure is the other label theme. The label says to avoid or minimize sunlight including sunlamps because of heightened sunburn susceptibility, that patients with sunburn should not use the cream until fully recovered, and that sunscreen with a minimum SPF of 15 plus protective clothing should be used; people with considerable occupational sun exposure or inherent sun sensitivity should exercise caution [2]. The cream should be kept out of the eyes, mouth, angles of the nose and mucous membranes [2].

For rosuvastatin, the main labeled concerns are muscle and liver. Myopathy and rhabdomyolysis can occur; risk factors include age 65 or older, uncontrolled hypothyroidism, renal impairment, certain other drugs and higher dosage, and Asian patients may be at higher risk [1]. The label says patients should promptly report unexplained muscle pain, tenderness or weakness, particularly with malaise or fever [1]. In pooled placebo-controlled trials, transaminases above 3 times the upper limit of normal occurred in 1.1% on Crestor versus 0.5% on placebo, and HbA1c and fasting glucose can rise [1].

The Crestor label says to assess LDL-C as early as 4 weeks after starting and to consider liver enzyme testing before starting and as clinically indicated [1].

The Bottom Line

No interaction between topical tretinoin and rosuvastatin is listed on either label. The Crestor label lists interactions with several other drugs, including cyclosporine, gemfibrozil, certain antivirals, antacids and warfarin [1]. The Renova 0.02% cream's documented interactions are skin irritants and photosensitizing drugs [2]. What each label documents for its own drug is tretinoin's local irritation and sun sensitivity, and rosuvastatin's muscle, liver and glucose effects [1][2].