2. Methods
In the present observational study, we considered and evaluated all reports of suspected ADRs collected in the COVID-19 Units of Careggi University Hospital, Florence (Italy), between January 1st and 31st May 2020. All suspected ADRs were collected from the clinical charts after a consultation performed by the Toxicology Unit on request of clinicians working in COVID-19 Units.
Following the Italian pharmacovigilance legislation [17], a multidisciplinary team composed by experts in pharmacovigilance (GC, AV, NL) and clinical toxicology (VB, CL, AB, AI, GM) provided their consultation and filled out the specific report form [18, 19], collecting information on: (1) patients’ demographic characteristics (age, gender, ethnic group); (2) patients’ clinical status; (3) suspected drugs and concomitant medications (for each one, administration route, therapy duration, dosages, and therapeutic indication were recorded); (4) ADRs description; (5) ADRs outcome (improvement, complete resolution, unchanged or worsened event, resolution with sequelae, death). A “suspected drug” is defined as a drug which is potentially associated with the observed ADR, while a “concomitant medication” is a drug the patient is exposed to at the time of ADR occurrence. A concomitant medication may not necessarily be associated to the ADR.
For each case included in the analysis the experts performed a medical evaluation in order to assess the causality relationship between the suspected drugs and their related ADRs according to the Naranjo’s scale [20]. Moreover, each case was evaluated with the aim of identifying the presence of DDIs, which may have contributed to ADRs. DDIs were identified using two different validated tools: (1) the open access Drug Interaction Checker [21], and (2) the drug interaction software Micromedex Drug-REAX System (Thomson Reuters Healthcare Inc., Greenwood Village, Colorado, United States), available online with restricted access. As reported in the Micromedex [22] and Drug Interaction [21] tools, DDIs were classified as mild, moderate, or major, depending on their clinical impact on patient.
Suspected drugs and concomitant medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. ADRs description according to diagnosis and symptoms was coded using the Medical Dictionary for Regulatory Activities (MedDRA) and organized by Preferred Term (PT) [23, 24].
Data are presented as number and percentages or, for continuous variables, as mean and standard deviation (SD).