Safety aspects of iodinated contrast media related to their physicochemical properties: a pharmacoepidemiology study in two Tuscany hospitals.
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.
Lapi
Francesco
F
Tuscan Regional Centre of Pharmacovigilance, Department of Pharmacology, University of Florence, Viale G. Pieraccini no. 6, 50139 Florence, Italy. francesco.lapi@unifi.it
Cecchi
Enrica
E
Pedone
Claudio
C
Attanasio
Francesco
F
Banchelli
Grazia
G
Vannacci
Alfredo
A
Di Pirro
Marina
M
Moschini
Martina
M
Berni
Valentina
V
Matucci
Rosanna
R
Cini
Elisabetta
E
Scalia
Antonino
A
Tendi
Enrico
E
Mugelli
Alessandro
A
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
D003287:Contrast Media; D007455:Iodine