Post-Marketing Surveillance of the Safety Profile of Iodixanol in the Outpatient CT Setting: A Prospective, Multicenter, Observational Study of Patient Risk Factors, Adverse Reactions and Preventive Measures in 9953 Patients

Abstract

Purpose: Non-interventional study in outpatient, contrast-enhanced CT

1. to determine the extent of preventive measures for risk reduction of adverse drug reactions after contrast-enhanced CT examinations.

2. to prospectively determine the incidence and severity of adverse drug reactions occurring after administration of the iso-osmolar contrast medium iodixanol

3. to determine a possible influence of preventive measures on the incidence/severity of adverse drug reactions.

Materials and Methods: Evaluable documentation was provided for 9953 patients from 66 radiology centers across Germany. Patient characteristics, aspects of iodixanol administration, and adverse events with an at least “possible” relationship were documented on a standardized case report form (CRF) and were evaluated up to seven days after contrast medium administration.

Results: About 55.5 % of patients showed one or more risk factors (e. g. impaired renal function 4.4 %, diabetes mellitus 8.5 %, hypertension 20.6 %). One third of the sites did not implement any preventive measures. Patients with a known risk for an allergy-like reaction were more likely to receive pharmacologic preventive treatment (0.5 – 50.5 %). Oral hydration was the main preventive measure in patients with renal risk factors (< 8 %) followed by intravenous hydration (1 %). Adverse drug reactions, mainly hypersensitivity reactions, occurred in 77 patients (0.74 %), but were classified as serious in only 3 patients (0.03 %). No statistically significant correlation between risk factors, preventive measures, and adverse reactions could be found.

Conclusion: The use of preventive measures for CT examinations in this outpatient setting was generally low with risk patients being pre-medicated more often, depending on their history. In the routine outpatient setting, iso-osmolar iodixanol was very well tolerated in almost 10 000 patients undergoing diagnostic CT. The rate of acute and delayed adverse reactions was low. No correlation could be found between risk factors, preventive measures and the incidence of adverse drug reactions.

Key Points:

• Rare use of preventive measures for outpatient CT examinations.

• Low rate of acute and late adverse drug reactions to iodixanol.

• No correlation between risk factors, preventive measures and adverse drug reactions.

Citation Format:

• Müller FHH. Post-Marketing Surveillance of the Safety Profile of Iodixanol in the Outpatient CT Setting: A Prospective, Multicenter, Observational Study of Patient Risk Factors, Adverse Reactions and Preventive Measures in 9953 Patients. Fortschr Röntgenstr 2014; 186: 1028 – 1034

Zusammenfassung

Ziel: Nicht-interventionelle Studie bei ambulanten, kontrastmittelunterstützten CT–Untersuchungen zur

1. Häufigkeitsabschätzung präventiver Maßnahmen zur Risikoreduktion von Nebenwirkungen

2. prospektive Erfassung von Nebenwirkungen (Häufigkeit und Schweregrad) nach Gabe des isoosmolaren Röntgenkontrastmittels Iodixanol

3. Abschätzung des Einflusses präventiver Maßnahmen auf Häufigkeit und Schwere der beobachteten Nebenwirkungen

Material und Methoden: Ausgewertet wurden die Angaben zu 9953 Patienten aus 66 radiologischen Zentren/Praxen in Deutschland. Patientencharakteristika und Applikationsparameter von Iodixanol sowie Reaktionen mit möglichem ursächlichen Zusammenhang mit Iodixanol wurden durch standardisierte Patientenbögen erfasst und bis zu sieben Tage nach Kontrastmittelapplikation ausgewertet.

Ergebnisse: Insgesamt zeigten 55,5 % der Patienten einen oder mehrere Risikofaktoren (z. B. 4,4 % eingeschränkte Nierenfunktion, 8,5 % Diabetes mellitus, 20,6 % erhöhten Blutdruck). Ein Drittel der Praxen setzte keinerlei präventive Maßnahmen ein. Patienten mit bekanntem Risiko für allergoide Reaktionen wurden häufiger medikamentös prämediziert (0,5 – 50,5 %). Häufigste präventive Maßnahme bei Patienten mit renalen Risikofaktoren war die orale (< 8 %), gefolgt von der intravenösen Hydrierung (1 %). Nebenwirkungen, überwiegend Hypersensitivitätsreaktionen, wurden für 77 Patienten berichtet (0,74 %), davon bei 3 Patienten (0,03 %) als schwerwiegend eingestuft.

Schlussfolgerung: Der Einsatz präventiver Maßnahmen bei ambulanten CT-Untersuchungen war insgesamt gering, bei Risikopatienten je nach Anamnese etwas häufiger. In der klinischen Routine bei ambulanten CT-Untersuchungen zeigte sich das isoosmolare Iodixanol bei annähernd 10 000 Patienten als sehr verträglich. Es konnte keine Korrelation zwischen Risikofaktoren, Präventivmaßnahmen sowie der Häufigkeit von Nebenwirkungen gefunden werden.

Kernaussagen:

• Präventivmaßnahmen selten bei ambulanten CT-Untersuchungen

• Geringe Rate an akuten und verzögerten Nebenwirkungen nach Iodixanol

• Kein erkennbarer Zusammenhang zwischen Risikofaktoren, Präventivmassnahmen und Nebenwirkungen

Key words

CT - contrast agents - drugs/reactions - iodixanol - post-marketing surveillance - safety profile

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