title: Safety aspects of iodinated contrast media related to their physicochemical properties: a pharmacoepidemiology study in two Tuscany hospitals.
abstract: BACKGROUND
  More than 380,000 angiographic procedures are performed every year in Italian hospitals, with an increase rate of 8% per year. Although contrast media (CM) are considered relatively safe, adverse drug reactions (ADRs) remain an important issue.
  
  
  OBJECTIVE
  The objective of this study was to quantify the incidence of immediate and delayed nonrenal ADRs to iodinated CM in an Italian cohort and to evaluate whether their different physicochemical properties are able to affect the incidence of immediate or delayed ADRs.
  
  
  METHODS
  A prospective intensive monitoring study was conducted on a cohort of patients undergoing radiodiagnostic procedures with iodinated CM enrolled in two hospitals in Tuscany, Italy. To evaluate both immediate (within 1 h after CM administration) and delayed (>1 h to 1 week after CM administration) ADRs to CM, two questionnaires were administered. Adverse events (AEs) were analyzed to check the causality assessment between CM and ADR. If more than one symptom occurred in the same patient, they were treated as a single event.
  
  
  RESULTS
  One thousand five hundred and fourteen subjects who were exposed to iodinated CM completed the questionnaires. Mean age [standard deviation (SD)] was 65.4 (13.3) years, and 57.9% were male patients. A total of 178 [11.8%; 95% confidence interval (CI) 10.1-13.4] ADRs were reported. Thirty-four (2.2%; 1.5-3.1) and 144 (9.5%; 8.0-11.1) developed immediate and delayed ADRs, respectively. Both types of ADRs were experienced by six subjects (0.4%; 0.1-0.8). One hundred and seventy-six cases (98.8%; 96.0-99.8) were classified as possible and two (1.1%; 0.1-3.9) as probable ADRs. Monomeric low-osmolal (iopromide, iomeprol, iobitridol) and dimeric iso-osmolal (iodixanol) groups mainly reported delayed allergy-like ADRs of mild severity. Only one immediate reaction was severe. Multivariate analysis confirmed a higher risk of immediate reactions occurring for monomeric CM (OR 4.3; 95% CI 1.2-15.7), whereas the risk of delayed ADRs was significantly higher for the dimeric group (OR 1.8; 1.1-2.5).
  
  
  CONCLUSIONS
  Monomeric CM were more frequently involved in immediate ADRs, whereas dimeric CM were involved in delayed reactions. Although severe life-threatening ADRs to CM were confirmed to be rare, due to the large use of these drugs, they still retain clinical and epidemiological significance.
authors.affiliation: Tuscan Regional Centre of Pharmacovigilance, Department of Pharmacology, University of Florence, Viale G. Pieraccini no. 6, 50139 Florence, Italy. francesco.lapi@unifi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Lapi
authors.forename: Enrica
authors.initials: E
authors.lastname: Cecchi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pedone
authors.forename: Francesco
authors.initials: F
authors.lastname: Attanasio
authors.forename: Grazia
authors.initials: G
authors.lastname: Banchelli
authors.forename: Alfredo
authors.initials: A
authors.lastname: Vannacci
authors.forename: Marina
authors.initials: M
authors.lastname: Di Pirro
authors.forename: Martina
authors.initials: M
authors.lastname: Moschini
authors.forename: Valentina
authors.initials: V
authors.lastname: Berni
authors.forename: Rosanna
authors.initials: R
authors.lastname: Matucci
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cini
authors.forename: Antonino
authors.initials: A
authors.lastname: Scalia
authors.forename: Enrico
authors.initials: E
authors.lastname: Tendi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000792:Angiography; D003287:Contrast Media / Q000009:adverse effects*; D005260:Female; D006761:Hospitals; D006801:Humans; D007455:Iodine / Q000009:adverse effects*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged
chemical_list: D003287:Contrast Media; D007455:Iodine