Risk of drug-induced photosensitivity: focus on spectroscopic and molecular characteristics

• Published in: Pharmacoepidemiology and drug safety 2009-07, Vol.18 (7), p.602-609
• Main Authors: Verdel, B.M., Souverein, P.C., Meyboom, R.H.B., Kardaun, S.H., Leufkens, H.G.M., Egberts, A.C.G.
• Format: Article
• Language: English
• Subjects: Absorption; Databases, Factual - statistics & numerical data; Drugs; Humans; molecular drug characteristics; pharmacovigilance; photosensitivity; Photosensitivity Disorders - chemically induced; Photosensitivity Disorders - epidemiology; Physicochemical properties; Prescription Drugs - adverse effects; Prescription Drugs - analysis; Prescription Drugs - chemistry; Risk Factors; Seasons; Side effects; Skin; spectroscopy; Spectrum Analysis - statistics & numerical data; ultraviolet radiation; Ultraviolet Rays - adverse effects; World Health Organization
• ISSN: 1053-8569; 1099-1557; 1099-1557
• DOI: 10.1002/pds.1760

Background Drug‐induced photosensitivity is difficult to predict and remains a challenge for both the dermatological clinical practice and pharmacovigilance. Purpose To assess the association between spectroscopic and molecular characteristics and the occurrence of photosensitivity reactions. Methods For 143 well‐known photosensitisers (e.g. tetracyclines, diuretics), we retrieved information on spectroscopic and molecular parameters, including: absorption maximum λmax, molar absorption coefficient ε, area under the absorption curve (AUC), molecular weight and configuration, hetero and aromatic halogen atoms, lipophilicity (log P) and acid/base status (pKa). In the WHO‐ADR database, all reports with suspected adverse drug reactions of the study drugs were selected. We identified all reports on photosensitivity reactions and defined them as cases. All other reports were selected as non‐cases. A case–non‐case approach was performed to assess the spectroscopic and molecular exposure variables as a factor for photosensitivity reactions. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Results A λmax between 290 and 320 nm (OR 3.74, 95% CI 3.45–4.06), and an ε > 20 000 M−1 cm−1 (OR 5.49, 95% CI 5.10–5.92) were highly associated with the reporting of photosensitivity reactions. Risk of the photosensitivity reactions was significantly increased among intermediate or high AUCs compared to low AUC. Low molecular weight and aromatic halogen atoms were associated with photosensitivity reactions (OR 2.37, 95% CI 2.07–2.71 resp. OR 3.37, 95% CI 3.15–3.61) as were log p