Evidence of the label ototoxicity in medicines marketed in Denmark

Summary Cisplatin and other ototoxic agents such as vancomycin, quinine, and carboplatin are widely used in medical treatments but pose a significant risk of ototoxicity. This literature review investigates the incidence, severity, and characteristics of drug induced ototoxicity of nine drugs listed in the Danish summary of product characteristics (SmPC's), where each was found to contain an unclear reference to ototoxic related side effect. The main objective was to identify patterns in ototoxic outcomes and assess the effectiveness of interventions aimed at reducing hearing damage. A systematic search identified nine clinical studies on ototoxic effects and four on preventive measures. Studies varied in design, ranging from retrospective reviews to randomized controlled trials, and included diverse patient populations, ages, and disease types. Data were extracted on dosage, type of ototoxicity, measurement methods, and statistical significance. Findings showed that cisplatin is consistently associated with dose dependent, often irreversible, bilateral hearing loss, with symptoms sometimes appearing weeks to months after treatment. Other agents like quinine and vancomycin presented more variable outcomes. Among preventive strategies, trans tympanic injections of N-acetylcysteine and sodium thiosulfate showed promising results in reducing cisplatin induced hearing loss, while oral antioxidants yielded limited effects. The review highlights methodological challenges, including heterogeneity in study design, limited follow up, and small sample sizes. There is also a possibility that additional relevant studies exist in other databases or under alternative search terms. Cisplatin presents the most well documented ototoxic profile, whereas the evidence for other drugs is either limited, variable, or lacking. These findings call for better harmonization between drug labelling and current clinical evidence, as well as improved monitoring and drug specific research to guide safer prescribing practices.