Late allergy-like reactions following vascular administration of radiography contrast media.

PURPOSE: To compare the frequency of allergy-like reactions in adults following vascular injection of iohexol and iopentol versus other contrast media (CMs), with emphasis on late reactions. MATERIAL AND METHODS: Thirty-two trials involving a total of 2,656 patients in the European clinical development programmes for iohexol and iopentol were retrospectively evaluated. The number of patients experiencing late allergy-like reactions, immediate allergy-like reactions, and both types of reaction were pooled separately. Late was defined as time of onset being 60 min or more after the first injection of CM. RESULTS AND CONCLUSION: After vascular administration of iohexol and iopentol, 0.52% (0.44% and 0.68% respectively) of the patients experienced a late allergy-like reaction. The same frequency was reported for immediate allergy-like reactions. After administration of ionic CMs, the frequency of late allergy-like reactions was in the same range (0.42%) as for non-ionic CMs, but the frequency of immediate allergy-like reactions was much higher (6.99% vs 0.52%). Our results are in the same range as those reported by other authors. No serious adverse reactions were reported in the 32-trial series.

Myelography with a dimeric (iodixanol) and a monomeric (iohexol) contrast medium: a clinical multicentre comparative study.

The purpose of this study was to evaluate and compare the radiographic efficacy and safety of iodixanol (Visipaque; 270 and 320 mg I/ml) and iohexol (Omnipaque; 300 mg I/ml) in myelography. The study was randomized, double-blind and comparative including 398 patients from five European university clinics. The radiographic visualisation was evaluated as poor, good or excellent. Adverse events were recorded by interviewing the patients after the myelography, and each patient was given a questionnaire to be returned after 1 week. In cervical myelography with cervical puncture more films with excellent quality was obtained after iodixanol 320 mgI/ml compared with iohexol 300 mgI/ml (p = 0.009). Also in lumbar myelography iodixanol 320 mgI/ml compared favourably with iohexol 300 mgI/ml (p = 0.006). The most frequent adverse event was headache, which occurred in 5-35 % of patients during the first 24 h and in 19-61 % within the first 7 days, depending on the centre. There was no difference in frequency and severity of the adverse effects between the contrast media.

A comparison of a non-ionic dimer, iodixanol with a non-ionic monomer, iohexol in low dose intravenous urography.

A prospective, double-blind study of 392 patients randomized into four groups was performed to establish whether diagnostic intravenous urograms could be obtained with a lower dose of iodine when using the dimeric, non-ionic contrast medium iodixanol compared with the monomeric, non-ionic iohexol. Patients received iodixanol or iohexol containing either 9 or 12 g of iodine (gI). The primary parameter was the diagnostic quality of the 6 min film, assessed in a blinded fashion, by consensus, by four radiologists. Iodixanol at both doses was diagnostic in over 90% of cases. Iohexol was only diagnostic in 74% (9 gI) and 81.8% (12 gI). Pairwise comparisons revealed that iodixanol 9 gI was significantly better than both iohexol 9 gI (p = 0.0005) and 12 gI (p = 0.014). No significant difference was present for different doses within the same contrast medium group. Iodixanol resulted in poorer bladder distension than iohexol. Iodixanol caused significantly less discomfort than iohexol.

Evaluation of the clinical safety of gadodiamide injection, a new nonionic MRI contrast medium for the central nervous system: a European perspective.

Gadodiamide injection is a new nonionic paramagnetic, extracellular contrast medium. Its safety at a dose of 0.1 mmol/kg body weight was evaluated in a large European multicentre trial on adults referred for contrast-enhanced MRI of the central nervous system. Safety analysis was performed on 2102 patients, in whom adverse events during and up to 24 h after injection were recorded. Adverse events related or possibly related to gadodiamide injection were observed in 102 patients. Injection-associated reactions classified as discomfort (sensation of heat or coldness, pain or pressure at the injection site) occurred in 37 patients (1.8%) and other adverse events (e.g. headache, nausea) were observed in 65 patients (3.1%). No serious adverse event was reported. Efficacy analysis, performed on 2273 patients, and based on comparison of T1- and T2-weighted images before and T1-weighted images after injection showed that more diagnostic information was obtained after gadodiamide injection in 1424 (62.6%) patients: management of 386 (17.0%) patients was affected by the new information given and that a new diagnosis was made in 755 (33.3%) patients. Gadodiamide injection was shown to be safe and well tolerated. It represents a nonionic alternative to the current products for MRI of the central nervous system.

Safety of gadodiamide injection in two different age groups.

A meta-analyses was performed to evaluate the safety of gadodiamide injection (OM-NISCAN) for magnetic resonance imaging in two different age groups (< 65 years; > or = 65 years). Data on vital signs, clinical laboratory parameters, and subjectively experienced adverse events were reviewed for 734 patients included in 19 European Phase II and III trials with gadodiamide injection (0.1 mmol/kg body weight or 0.3 mmol/kg body weight) used in magnetic resonance imaging. One hundred sixty-four patients were 65 years of age or older. No statistically significant differences were shown between this population and the population younger than 65 years of age with respect to vital signs or clinical laboratory parameters. A total of 48 adverse events, discomfort excluded, were reported, with no significant difference in frequency between the two age groups. Injection-associated discomfort was significantly (P = .0025) more frequent in the younger (9.2%) than in the older group (2.5%). Gadodiamide injection is in conclusion a safe contrast medium in older as well as in younger patients.

Comparison of the safety of standard and triple dose gadodiamide injection in MR imaging of the central nervous system. A double-blind study.

Gadodiamide injection was administered intravenously to 49 patients with known or suspected CNS lesions undergoing MR imaging. Two parallel groups were used to evaluate the efficacy and safety of single doses of 0.1 (25 patients) and 0.3 (24 patients) mmol/kg b.w. The principal measures of efficacy were diagnostic yield of MR and the overall contrast enhancement. Adverse events and serum bilirubin were the main safety parameters. Contrast enhancement of the lesion was observed for 16 patients in each dose group. Thirteen patients in the 0.1 and 17 in the 0.3 mmol/kg group had their diagnosis amended following the postcontrast image, but only one patient in each dose group had their management affected by new information from the postcontrast image. The overall diagnostic utility of gadodiamide injection was good, but there were no differences between the 2 doses studied in this respect. No injection-associated discomfort or other adverse events were reported. No clinically important changes in serum bilirubin, or other parameters of blood chemistry, or hematology were observed. Overall, the safety profile of gadodiamide injection 0.3 mmol/kg b.w. in this study was similar to that of 0.1 mmol/kg b.w.

Comparison of the safety of the standard dose and a higher dose of gadodiamide injection for MR imaging of the central nervous system.

This study compared the safety and tolerability of gadodiamide injection at the standard dose (0.1 mmol/kg) and at a higher dose (0.3 mmol/kg) in 289 patients participating in a parallel group multiple independent trial program. All patients had a known or suspected central nervous system lesion necessitating investigation with contrast medium-enhanced magnetic resonance imaging. Safety assessments were made before and after injection of the contrast medium, and 1 day later. No adverse events were judged to be related to gadodiamide injection, and only 3.5% of the patients in each dose group reported adverse events that had an uncertain relationship to the contrast medium; both doses were therefore well tolerated. Headache was the most frequently reported event (2%). There were no significant injection-related changes in neurologic status, laboratory test results, or vital signs. The data obtained indicate that the higher dose of gadodiamide injection is as safe and well tolerated as the standard dose.

A double-blind, comparative study of gadodiamide injection and gadopentetate dimeglumine in MRI of the central nervous system.

Seventy-nine patients with known or suspected central nervous system lesions were studied with MRI in a phase III double-blind study. Forty were given gadopentetate dimeglumine (Gd-DTPA) and 39 gadodiamide injection (Gd-DTPA BMA), a new low-osmolar nonionic contrast enhancing medium. The dosage was 0.1 mmol/kg body weight, corresponding to 0.2 ml/kg. Spin-echo sequences were performed before and immediately after injection. The safety and efficacy of the two contrast media were assessed. No changes were observed in blood pressure, heart rate or neurological status. Five adverse effects (two episodes of headaches, two of nausea and one of dizziness) were reported by 2 patients who received gadodiamide injection and 1 who received gadopentetate dimeglumine. All events were mild and their relationship to the contrast media was uncertain. For both contrast media statistically significant changes in serum iron were observed 24 h after injection. More than 70% of the patients had abnormal findings on MRI, and in 56% of these contrast enhancement of the abnormal structure or lesion was seen. Contrast enhancement provided the diagnosis in about 50%, changed it in 40% and increased diagnostic confidence in 95%.

Pharmacokinetics of iopentol in patients with chronic renal failure.

Iopentol 350 mg I/ml was injected in doses of 265 to 533 mg I/kg b.w. (mean 417 mg I/kg b.w.) in 10 patients with advanced nondiabetic chronic renal failure (S-creatinine 672 +/- 259 mumol/l (mean +/- SD)). Urine (10 patients) and feces (7 patients) were collected at 24 h intervals for 5 days after the injection. The elimination of iopentol was delayed. Five days after injection a mean of 54% (range 35-79%) of the dose was recovered in urine, and 11% (0-20%) in feces. Mean elimination half-life was 28.4 h, about 14 times the half-life found in healthy volunteers. The apparent volume of distribution was 0.27 l/kg b.w., indicating distribution only to extracellular fluid. Using renal iopentol clearance as reference value, GFR was overestimated by 40 to 60% with iopentol total clearance, showing extrarenal elimination of iopentol. The difference was most pronounced in patients with low GFR. In conclusion, this study shows an extrarenal elimination of iopentol and demonstrates a substantial increase in the fecal elimination in patients with severe renal failure.

Iopentol in patients with chronic renal failure: its effects on renal function and its use as glomerular filtration rate parameter.

Iopentol (mean dose 0.42 g I kg-1) was administered for abdominal aortography and pelvic angiography in 10 patients with advanced non-diabetic chronic renal failure (S-creatinine 672 +/- 259 mumol l-1, mean +/- SD). Renal glomerular function measured as creatinine clearance and plasma clearance of [99Tcm]-diethyl-enetriaminepentaacetic acid (DTPA) was unchanged by iopentol, as also was urinary excretion of the renal tubular enzymes N-acetyl-beta-glucosaminidase (NAG) and alkaline phosphatase (ALP). The elimination of iopentol from serum and urine was delayed, and detectable serum and urine concentrations were found 5 days after administration of the contrast medium. Creatine clearance was 47% higher than the corresponding renal iopentol clearance. Plasma iopentol clearance, measured as the total area under the plasma concentration curve, was 40% higher than renal iopentol clearance because of extrarenal elimination of iopentol. We conclude that abdominal aortography with iopentol can be performed without effects on renal glomerular or tubular function parameters in patients with advanced renal failure. If iopentol is used for measurement of glomerular filtration rate (GFR) in this group of patients, one should measure renal clearance, as plasma clearance overestimates GFR.

Human pharmacokinetics of iodixanol.

The pharmacokinetic properties of the x-ray contrast medium, iodixanol, a new nonionic dimer, were investigated in a phase I study including 40 healthy male volunteers. Iodixanol (300 mg I/mL) was administered intravenously (i.v.) at four dose levels--0.3, 0.6, 0.9, and 1.2 g iodine (I)/kg body weight--and saline was given as a control. 51Cr-EDTA was given concomitantly with iodixanol at all dose levels to study renal excretion of iodixanol. Mean half-lives were 26 and 131 minutes in the distribution and elimination phase, respectively. Apparent volume of distribution was 0.28 1/kg body weight, indicating distribution to extracellular fluid only. Within 24 hours after injection, 97% of the dose was excreted unmetabolized in the urine via glomerular filtration. The excretion in feces was 1.2% of the dose. The parameters calculated were independent of the given dose. The pharmacokinetics of iodixanol are comparable with those reported for other intravascular contrast media.