Tretinoin and Trazodone Interaction: What Patients and Prescribers Need to Know

Is there a known interaction?

The trazodone label's drug interaction table covers MAOIs (contraindicated), other serotonergic drugs, antiplatelets and anticoagulants, strong CYP3A4 inhibitors and inducers, digoxin, phenytoin, other QT-prolonging drugs and CNS depressants [1]. Tretinoin is not among them. The label describes trazodone as a CYP3A4 substrate: strong CYP3A4 inhibitors raise its exposure and strong inducers lower it [1]. Trazodone can also increase digoxin or phenytoin levels, and its label does not state how [1].

The Renova interaction section covers irritating topical products, strong drying products and drugs known to be photosensitizers. Trazodone is not named [2].

Does trazodone cause photosensitivity?

The skin-related entries in the trazodone label are allergic skin condition or edema, reported in 7% of outpatients on trazodone versus 1% on placebo, plus postmarketing reports of alopecia, hirsutism, leukonychia, pruritus, psoriasis, rash and urticaria. The label does not link these to sun exposure [1].

The Renova label addresses sun sensitivity for tretinoin. It warns of heightened sunburn susceptibility and says exposure to sunlight including sunlamps should be avoided or minimized. It also says the cream should not be administered to patients taking drugs known to be photosensitizers, such as thiazides, tetracyclines, fluoroquinolones, phenothiazines and sulfonamides, because of possible augmented phototoxicity [2].

How much tretinoin gets into the blood?

In seven healthy men, less than 2% of an applied dose of a 0.05% tretinoin cream was absorbed after a single application and after 28 days of daily use, and bioavailability was lower with repeated use. No percutaneous absorption study was conducted with Renova 0.02% itself [2]. Across formulations the label cites 1% to 31% of the applied dose, depending on whether skin was healthy or dermatitic [2].

What does the Renova label say about use?

The Renova label says to apply a light covering to the face once daily in the evening, after washing with a mild soap, patting dry and waiting 20 to 30 minutes. It also calls for sunscreen of at least SPF 15 and protective clothing [2].