The phenomenon of phototoxicity and long-term risks of commonly prescribed and structurally diverse drugs

Photosensitivity to structurally diverse drugs is a common but under-reported adverse cutaneous reaction and can be classified as phototoxic or photoallergic. Phototoxic reactions occur when the skin is exposed to sunlight after administering topical or systemic medications that exhibit photosensitizing activity. These reactions depend on the dose of medication, degree of exposure to ultraviolet light, type of ultraviolet light, and sufficient skin distribution volume. Accurate prediction of the incidence and phototoxic response severity is challenging due to a paucity of literature, suggesting that phototoxicity may be more frequent than reported. This paper reports an extensive literature review on phototoxic drugs; the review employed pre-determined search criteria that included meta-analyses, systematic reviews, literature reviews, and case reports freely available in full text. Additional reports were identified from reference sections that contributed to the understanding of phototoxicity. The following drugs and/or drug classes are discussed: amiodarone, voriconazole, chlorpromazine, doxycycline, fluoroquinolones, hydrochlorothiazide, nonsteroidal anti-inflammatory drugs, and vemurafenib. In reviewing phototoxic skin reactions, this review highlights drug molecular structures, their reactive pathways, and, as there is a growing association between photosensitizing drugs and the increasing incidence of skin cancer, the consequential long-term implications of photocarcinogenesis.