A systematic review of the incidence of hypersensitivity reactions and post-contrast acute kidney injury after ioversol in more than 57,000 patients: part 1-intravenous administration.

OBJECTIVES: To evaluate the incidence of adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs) and post-contrast acute kidney injury (PC-AKI), after intravenous (IV) administration of ioversol. MATERIALS AND METHODS: A systematic literature search (1980-2021) of studies documenting IV use of ioversol and presence or absence of ADRs, HSRs, or PC-AKI was performed. Key information including patients' characteristics, indication and dose of ioversol, safety outcome incidence, intensity and seriousness were extracted. RESULTS: Thirty-one studies (> 57,000 patients) were selected, including 4 pediatric studies. The incidence of ADRs in adults was reported in 12 studies from ioversol clinical development with a median (range) of 1.65% (0-33.3%), and 3 other studies with an incidence between 0.13 and 0.28%. The incidence of HSRs (reported in 2 studies) ranged from 0.20 to 0.66%, and acute events (4 studies) from 0.23 to 1.80%. Severe reactions were rare with a median (range) of 0 (0-4%), and none were reported among pediatric patients. The incidence of ADRs and HSRs with ioversol, especially those of severe intensity, was among the lowest in studies comparing different iodinated contrast media (ICM) of the same class. PC-AKI incidence was variable (1-42% in 5 studies); however, ioversol exposure per se did not increase the incidence. CONCLUSIONS: When administered by the IV route, ioversol has a good safety profile comparable to that of other ICM within the same class, with a low incidence of severe/serious ADRs overall, and particularly HSRs. PC-AKI incidence does not seem to be increased compared to patients who did not receive ioversol. Further well-designed studies are warranted to confirm these results. KEY POINTS: • Ioversol has a good safety profile in adult and pediatric patients when IV administered. • ADR and HSR incidence with ioversol, especially those of severe intensity, was among the lowest compared to other ICM. • IV administration of ioversol per se did not increase PC-AKI incidence.

A systematic review of the incidence of hypersensitivity reactions and post-contrast acute kidney injury after ioversol: part 2-intra-arterial administration.

OBJECTIVES: To evaluate the incidence of adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs) and post-contrast acute kidney injury (PC-AKI), after intra-arterial (IA) administration of ioversol. METHODS AND MATERIALS: A systematic literature search was performed (1980-2021) and studies documenting IA use of ioversol, and reporting safety outcomes were selected. Key information on study design, patients' characteristics, indication, dose, and type of safety outcome were extracted. RESULTS: Twenty-eight studies (including two pediatric studies) with 8373 patients exposed to IA ioversol were selected. Studies were highly heterogenous in terms of design, PC-AKI definition, and studied population. PC-AKI incidence after coronary angiography was 7.5-21.9% in a general population, 4.0-26.4% in diabetic patients, and 5.5-28.9% in patients with chronic kidney disease (CKD). PC-AKI requiring dialysis was rare and reported mainly in patients with severe CKD. No significant differences in PC-AKI rates were shown in studies comparing different iodinated contrast media (ICM). Based on seven studies of ioversol clinical development, the overall ADR incidence was 1.6%, comparable to that reported with other non-ionic ICM. Pediatric data were scarce with only one study reporting on PC-AKI incidence (12%), and one reporting on ADR incidence (0.09%), both after coronary angiography. CONCLUSIONS: After ioversol IA administration, PC-AKI incidence was highly variable between studies, likely reflecting the heterogeneity of the included study populations, and appeared comparable to that reported with other ICM. The rate of other ADRs appears to be low. Well-designed studies are needed for a better comparison with other ICM. KEY POINTS: • PC-AKI incidence after IA administration of ioversol appears to be comparable to that of other ICM, despite the high variability between studies. • The need for dialysis after IA administration of ioversol is rare. • No obvious difference was found regarding the safety profile of ioversol between IA and IV administration.

Baseline characteristics, diagnostic efficacy, and peri-examinational safety of IV gadoteric acid MRI in 148,489 patients.

BACKGROUND: Magnetic resonance imaging (MRI) examinations with intravenous (IV) contrast are performed worldwide in routine daily practice. In order to detect and enumerate even rare adverse events (AE) and serious adverse events (SAE), and to relate them with patients' baseline characteristics and diagnostic effectiveness, high quantity sample size is necessary. PURPOSE: To assess safety, diagnostic effectiveness, and baseline characteristics of patients undergoing IV gadoteric acid (Dotarem®) MRI in routine practice. MATERIAL AND METHODS: Data from two observational post-marketing surveillance (PMS) databases compiled by 139 and 52 German centers in 2004-2011 and 2011-2013, respectively, were pooled, yielding data on a total of 148,489 patients examined over a 10-year period. Radiologists used a standardized questionnaire to report data including patient demographics, characteristics of MR examinations, and results in terms of diagnosis and patient safety. RESULTS: Overall, 712 AEs were reported in 467 (0.3%) patients, mainly nausea (n = 224, 0.2%), vomiting (n = 29, <0.1%), urticaria (n = 20, <0.1%), and feeling hot (n = 13, <0.1%). AEs were considered related to gadoteric acid in 362 (0.2%) patients. Higher frequencies of AEs were observed among patients with a previous reaction to a contrast agent (2.0%), liver dysfunction (0.7%), bronchial asthma (0.7%), and a history of allergies (0.6%). There were 49 SAEs in 18 (<0.1%) patients, including two children. No fatal SAE was reported. Examinations were diagnostic in 99.8% of all patients, and image quality was excellent or good in 97.7% of the patients. CONCLUSION: Gadoteric acid is a safe peri-examinational and effective contrast agent for MRI in routine practice.

Safety Analysis of Iobitridol as a Nonionic Contrast Medium: A Postmarketing Multicenter Surveillance Study With 94,960 Patients Almost 20 Years After Introduction.

OBJECTIVES: Our study sought to reevaluate the safety and diagnostic efficacy of iobitridol as a nonionic contrast medium after almost 20 years of use. MATERIALS AND METHODS: This noninterventional postmarketing surveillance noncontrolled, multicenter (168 centers in Germany) study enrolled 94,960 patients receiving intravenous or intra-arterial iobitridol. The majority of the adjusted population (n = 92,550, 98.2%) underwent either computed tomography examination (n = 46,502, 49.3%) or intravenous urography (n = 46,048, 48.8%). A standardized questionnaire was used to ascertain patient's information, known risk factors, renal function status, premedication, type of examination, injection of contrast agent, imaging quality, diagnostic value, and safety. RESULTS: A total of 469 patients (0.49%) experienced an adverse event (AE), and 24 patients (0.025%) reported a serious AE (SAE). All patients recovered and no fatal event occurred. The prevalence of AE was significantly higher in patients with at least one risk factor, with premedication, with a history of AE, in female and patients younger than 60 years old (P < 0.05). Presence of at least one risk factor is the only predictive factor for the prevalence of SAE (P = 0.042). In patients with a history of AE, premedication did not significantly lower the AE rate (P = 0.737). No statistically significant difference in the prevalence of AE between the different combination of cortisone and/or antihistamines as pretreatment was found. CONCLUSIONS: Iobitridol is a safe contrast medium with a high tolerability and efficacy. Presence of risk factors such as cardiovascular diseases, allergies, or asthma was the only significant predictive factor for an AE and an SAE. Premedication did not significantly lower the occurrence of an AE and an SAE.