Phototoxicity has been attributed to numerous oral drugs over the past 60 years.

Determine the quality of evidence supporting suspected phototoxicity from oral drugs.

The MEDLINE and EMBASE databases were searched for all studies that contain original data for drug-induced phototoxicity and were published between May 1959 and December 2016. Study quality was assessed by using a modified Grading of Recommendations, Assessment, Development and Evaluation scale.

The review included 240 eligible studies with a total of 2466 subjects. There were 1134 cases of suspected phototoxicity associated with 129 drugs. Most associations were supported by either very low-quality or low-quality evidence (89.1% of the studies). Medications supported by stronger evidence were vemurafenib, nonsteroidal anti-inflammatory drugs, and antibiotics, specifically, fluoroquinolones and tetracyclines. The most frequently reported drugs were vemurafenib, voriconazole, doxycycline, hydrochlorothiazide, amiodarone, and chlorpromazine. Photobiologic evaluation was performed in only 56 studies (23.3%), whereas challenge-rechallenge was done in 10% of cases.

Only English-language publications were reviewed. Cases of phototoxicity that had been incorrectly categorized as photoallergy would not have been included.

Most purported associations between oral drugs and phototoxicity are not supported by high-quality evidence. Despite the variable quality of data, clinicians should be aware of the possible consequences of long-term use of culprit drugs.