Tretinoin and Nicotine Interaction Profile: What Patients and Clinicians Need to Know

Is There a Pharmacokinetic Interaction Between Tretinoin and Nicotine?

No pharmacokinetic interaction has been established between topical tretinoin and nicotine. The Renova 0.02% cream label's drug-interaction section names other topical medications, medicated or abrasive soaps and cleansers, strong-drying cosmetics, products with high concentrations of alcohol, astringents, spices or lime, permanent wave solutions, electrolysis, hair depilatories or waxes, and drugs known to be photosensitizers such as thiazides, tetracyclines, fluoroquinolones, phenothiazines, and sulfonamides [1]. Nicotine is not named.

Absorption through the skin is variable. The Renova 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 or dermatitic skin. No percutaneous absorption study was conducted with Renova 0.02% in human volunteers. For a different formulation, a 0.05% cream, absorption was less than 2% in healthy male volunteers after a single application and after repeated daily application for 28 days [1].

Nicotine follows a different metabolic route. It is a CYP2A6 substrate [4]. The well-described smoking interaction is not a nicotine effect: polycyclic aromatic hydrocarbons in tobacco smoke induce CYP1A2, and a review of smoking cessation states that the enzyme effect is not related to the nicotine component of tobacco, so nicotine replacement will not alter it [5][6].

Does Smoking Change How Tretinoin Works?

Smoking changes the tissue environment and healing response. A systematic review found that smoking temporarily decreases tissue oxygenation and aerobic metabolism, and that smoking cessation restores tissue oxygenation and metabolism rapidly. The inflammatory cell response reversed in part within 4 weeks, while the proliferative response remained impaired. In that review, nicotine did not affect the tissue microenvironment but appeared to impair inflammation and stimulate proliferation, with a marginal effect [3].

Nicotine also has cardiovascular effects: peripheral vasoconstriction, tachycardia, and higher blood pressure, with no tolerance to its catecholamine-releasing effects [2]. Those findings describe smoking and nicotine biology. They do not measure how much topical tretinoin improves acne or fine wrinkles in a person who smokes.

What Does the Tretinoin Label Warn About?

The Renova 0.02% cream label calls tretinoin a dermal irritant. It warns about severe local erythema, pruritus, burning, stinging, and peeling at the application site, and it says tretinoin has been reported to cause severe irritation on eczematous skin [1]. It should be kept out of the eyes, mouth, angles of the nose, and mucous membranes [1].

Photosensitivity is a separate label warning. The label says exposure to sunlight, including sunlamps, should be avoided or minimized, and that sunscreen with a minimum SPF of 15 and protective clothing should be used. Patients with sunburn should not use the product until fully recovered. People with considerable sun exposure through work or with inherent sun sensitivity should use caution [1].

The Renova label's warnings center on local irritation and UV exposure, not on tobacco use [1].

What About Nicotine Replacement, Gum, or Patches?

Nicotine replacement does not cause the CYP1A2 induction seen with smoking, because that induction is attributed to combustion products in smoke rather than nicotine [5][6].

A review of nicotine cardiovascular toxicity found that cigarette smoke contains many potential cardiovascular toxins besides nicotine. Regular smoking generally delivers higher nicotine doses than nicotine replacement, and the cardiovascular effects are more intense when nicotine is delivered rapidly by smoking than by transdermal nicotine or gum. In trials of patients with stable coronary disease, nicotine replacement did not appear to increase cardiovascular risk; at worst, the risk was no more than that of smoking [7]. The same review notes that cigarette smoking increases blood coagulability, whereas transdermal nicotine does not appear to do so [7].

What Skin Reactions Should a Person Using Tretinoin Expect?

The main skin issue is tretinoin irritation. In Renova trials involving 339 patients, almost all reported one or more local reactions such as peeling, dry skin, burning, stinging, erythema, and pruritus. In 32% of all study patients, skin irritation was severe, led to temporary discontinuation, or led to use of a mild topical corticosteroid. About 4% discontinued because of adverse reactions [1].

The label also says that applying larger amounts than recommended has not been shown to give faster or better results, and may cause marked redness, peeling, or discomfort [1].