SAFETY OF GADOLINIUM-DTPA - EXTENDED CLINICAL-EXPERIENCE

This review reports data on the general and renal tolerance of the paramagnetic contrast agent Gd‐DTPA after intravenous administration. Gd‐DTPA was administered usually at a dose level of 0.1‐0.2 mmol/kg body wt (range: 0.005‐0.25 mmol/kg body wt) in cranial, spinal and body MR indications. In phase I‐IIIa studies a total of 2154 healthy volunteers and patients were investigated, usually at a dose of 0.1 mmol/kg body wt. From the obtained results it was concluded that adverse events (AEs) may be expected in the order of magnitude of 1%. In phase IIIb‐IV studies 13,439 patients were investigated at 0.1 or 0.2 mmol/kg body wt. Tolerance data were collected according to a standardized protocol and metaanalysis of obtained data was performed. AEs, irrespective of their drug relationship, were observed in 1.15% of the patients. The observed AEs were comparable to those after intravenous administration of iodinated nonionic X‐ray contrast media. There was no correlation between patient age and the incidence of AEs. In patients with a known history of allergy the incidence of AEs increased to 2.6%. In pediatric use no added risk was observed in a total of 826 neonates, children, and adolescents up to 18 years of age. Gd‐DTPA showed good renal tolerance in patients with and without preexisting impairment of renal function. A prospective open safety and pharmacokinetic study was conducted in patients with hemodialysis. Gd‐DTPA was shown to be eliminated completely by hemodialysis. Fast bolus injections were tolerated without added risk. Presented data from postmarketing surveillance (up to March 31, 1991) cover an estimated total of more than 2,000,000 applications. In conclusion, Gd‐DTPA showed an excellent safety profile after intravenous administration of diagnostic doses to patients of all age groups, irrespective of the injection speed and preexisting renal impairment. The overall incidence of AEs after intravenous injection of 0.1 or 0.2 mmol Gd‐DTPA/kg body wt was found to be 1–2%. © 1991 Academic Press, Inc. Copyright © 1991 Wiley‐Liss, Inc., A Wiley Company