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).