Background and aim: The search for early and emergency effective treatments for COVID-19 infection may have led to loss of sight of treatments safety. In addition, characteristics of drug-drug interactions (DDIs)-related adverse drug reactions (ADRs) in COVID-19 patients have not yet been studied in depth. The aim of the present case-series study is to describe clinical and pharmacological characteristics of SARS-CoV-2 inpatients, focusing on ADRs, particularly those related to DDIs. Methods: We evaluated all reports of COVID-19 medications-related ADRs collected within the COVID-19 Units of Careggi University Hospital, Florence (Italy), between January 1st and 31st May 2020. Information regarding COVID-19 medications, patients’ demographic and clinical characteristics, concomitant drugs, ADRs description and outcome, were collected. Each case was evaluated for the causality assessment and to identify the presence of DDIs. Results: During the study period, 23 Caucasian patients (56.5% males, mean age 76.1 years) experienced one or more ADRs. The majority of them were exposed to polypharmacy and 17.4% presented concomitant conditions. ADRs were referred to cardiovascular, psychiatric and gastrointestinal disorders. The most frequently reported preferred term was QT prolongation (mean QT interval 496.1 msec). ADRs improved or resolved completely in 60.8% of cases. For all patients, a case-by-case evaluation revealed the presence of one or more DDIs, especially those related to pharmacokinetic interactions. Conclusions: Despite the small number of patients, our evidence underline the clinical burden of DDIs in SARS-CoV-2 inpatients and the risk of unexpected and uncommon psychiatric ADRs.