Retrospective survey of iotrolan 280-induced late adverse reactions

This survey aimed to evaluate the safety of the dimeric contrast agent iotrolan 280 by comparing the adverse reactions with those induced by non-ionic monomeric contrast agents used during the same period of time. The survey was performed by the University of Occupational and Environmental Health. All inpatients underwent intravenous CT or angiography with non-ionic contrast media. The contrast agents used were iotrolan 280 and the monomers iopamidol 300 and iohexol 300. Sixty-four patients received iotrolan 280 and 72 patients received a monomer. The incidence of adverse reactions in the iotrolan 280 group was 7 out of 64 patients (10.9 %) and 6 out of 72 patients (8.3 %) in the monomer group. In the iotrolan 280 group there were no early (within 1 h after injection of the contrast medium) adverse reactions but there were seven (10.9 %) late adverse reactions (more than I h after injection of the contrast medium). In the monomer group there were two (2.8 %) patients with early adverse reactions and four (5.6 %) with late adverse reactions. The late adverse reactions of the iotrolan 280 group consisted of four (6.3%) cases of skin symptoms and three (4.7 %) of other symptoms. In the monomer group there were three (4.2%) with skin symptoms and one (1.4%) with other symptoms. The background of the patients with late adverse reactions in the iotrolan 280 group showed five with a history of allergy and four with earlier exposure to contrast media. Two patients, both with a history of allergy and an earlier exposure to contrast media, showed adverse reactions. In the monomer group, similar historical background was found in the patients with late adverse reactions. The sites of the skin reactions in the iotrolan 280 group were mainly distributed on the head, neck, trunk and upper limbs. In the monomer group mainly the trunk was affected. In conclusion the overall incidence of adverse reactions was 10.9 % for the dimeric contrast agent and 8.3 % for the monomeric contrast agents. Late adverse reactions occurred in 10.9 % of the dimeric contrast agent patients and 5.6 % of the monomeric group patients. When cases with 'unknown' causal relationships were excluded, the incidence of adverse reactions was 7.8 % for the dimeric agent and 5.6 % for the monomeric agents. The adverse reactions associated with the use of the dimeric agent were all of late onset. In most of the late adverse reaction cases, histories of allergic reactions and previous contrast agent exposure were found. While most of the 'skin symptoms' induced by the monomeric agents occurred on the trunk, the sites of the skin symptoms due to the dimeric agent were so varied that they occurred not only on the trunk but also on the head and neck as well as the upper limbs. Table 1 gives a concise overview of the results of the main surveys of late adverse reactions induced by non-ionic monomeric contrast agents in Japan.