Onset of late adverse drug reactions to dimeric non-ionic contrast media: iotrolan, iodixanol.
The problem of late adverse drug reactions to X-ray contrast media (CM) has increasingly been of concern due to several reports of such ADRs to the newer dimeric nonionic CM iotrolan (280 mg iodine/ml) and iodixanol (150/270/320 mg iodine/ml). Precise information about the time of onset of late reactions would be helpful for defining the necessary post-investigational observation period in normal usage as well as in future clinical studies with these CM. We surveyed a total of 1135 ADR reports associated with iotrolan 280 and 1354 reports associated with iodixanol 150/270/320, compiled from clinical experimental studies, observational post marketing studies (PMS) and from spontaneous reporting systems (SRS). Late ADRs (i.e. ADRs observed later than 1 h post injection (p.i.)) associated with iotrolan 280 have been observed in about 55% of cases from PMS and in 70% of cases from SRS. For iodixanol 150/270/320 late ADRs were observed in 48% of cases from clinical experimental studies, in 29% of cases from PMS and of 63% cases from SRS. The analysis of time patterns of ADR onset of both CM revealed that most of the late ADRs were observed in the first 24-h period which is the standard observation time in most clinical studies with CM. However, a few cases of late ADRs were observed between 24 and 72 h p.i. and single cases later than 72 h p.i. Therefore, in future clinical studies with dimeric CM patients should be observed for at least 72 h after the investigation.
Pohly
J P
JP
Federal Institute of Drugs and Medical Devices, Berlin, Germany.