Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2017 Publisher: GE Healthcare, 8 Tangihua Street, PO Box 106911, Auckland 1010, Ph 0800 659465, Fax (09) 353-6701
Pharmacotherapeutic group: X-ray contrast media, iodinated
ATC code: V08AB09
VISIPAQUE is a dimeric, non-ionic, water-soluble, radiographic contrast medium with a molecular weight of 1550.20 (iodine content 49.1%). The organically bound iodine absorbs radiation in the blood vessels/tissues when it is injected.
For most of the haemaodynamic, clinical-chemical and coagulation parameters examined following intravenous injection of iodixanol in healthy volunteers, no significant deviation from pre-injection values has been found. The few changes observed in laboratory parameters were minor and considered to be of no clinical importance.
In a study involving 129 diabetic patients with serum creatinine levels of 1.5-3.5 mg/dl, use of VISIPAQUE resulted in 3% of patients experiencing a rise in creatinine of ≥0.5 mg/dl and no patients with a rise of ≥1.0 mg/dl. The peak increase in the serum creatinine concentration within three days after the administration of VISIPAQUE was 0.13 mg per dl (11.2 µmol per litre). A transient increase in tubular enzyme excretion was observed after contrast media injection. However, lower or similar effects on the release of enzymes (alkaline phosphatase and N-acetyl-ß-glucosaminidase) from the proximal tubular cells were observed for VISIPAQUE in comparison to ioxaglate.
Cardiovascular parameters such as LVEDP, LVSP, heart rate and QT-time as well as femoral blood flow were less influenced after VISIPAQUE than after other contrast media, where measured.
The safety and efficacy of VISIPAQUE has been established in the paediatric population for arterial studies, for intravenous procedures and gastrointestinal use. Use of VISIPAQUE in these age groups is supported by evidence from adequate and well controlled studies of VISIPAQUE in adults and additional safety data obtained in paediatric studies.
The clinical development of VISIPAQUE comprised: one pharmacokinetic study in 43 subjects and another ten clinical studies to demonstrate efficacy and safety of VISIPAQUE.
Six studies for intavenous use (two urography studies, four CT studies), two studies for intraarterial use (two cardioangiography studies) and two studies for gastrointestinal use. In two of these studies there was a pilot part including 3 and 10 patients, respectively. Otherwise the studies were phase III, randomized, double-blind,parallel-group comparison between iodixanol (VISIPAQUE) and iohexol (OMNIPAQUE).
A total of 638 infants and children were included in the clinical trials. They aged between birth and up to 17 years, 225 of them were younger than 24 months. Of these 403 received iodixanol and 235 patients received iohexol. The patients were equally distributed concerning age, sex and body weight in all study groups. Neonates were not enrolled in these studies with no child included with body weight <2 kg.
All the intravascular studies (intravenous and intra-arterial) showed that iodixanol was efficacious. No significant differences were detected between the iodixanol and iohexol groups. VISIPAQUE also gave appropriate contrast in all areas of the gastrointestinal tract and was found to be well suited for gastrointestinal examinations in the paediatric population. VISIPAQUE can also be used safely in the paediatric population.
Iodixanol is rapidly distributed in the body with a mean distribution half-life of approximately 21 minutes. The apparent volume of distribution is of the same magnitude as the extracellular fluid (0.26 Ι/kg b.w.), indicating that iodixanol is distributed in the extra-cellular volume only.
VISIPAQUE displayed no protein binding in vitro (less than 2% detectable limit) at a 1.2 mg I/ml concentration in human plasma. No significant metabolism, de-iodination or biotransformation has been detected in animals.
The mean elimination half-life is approximately 2 hours. Iodixanol is excreted mainly through the kidneys by glomerular filtration. Approximately 80% of the administered dose is recovered unmetabolised in the urine within 4 hours and 97% within 24 hours after intravenous injection in healthy volunteers. Only about 1.2% of the injected dose is excreted in faeces within 72 hours. The maximum urinary concentration appears within approximately 1 hour after injection.
No dose dependent kinetics have been observed in the recommended dose range.
Forty three (43) paediatric patients <12 years old, with renal function that is normal for their age, received multiple intra-arterial administrations of VISIPAQUE Injection in doses of 0.32 to 3.2 g I/kg body weight. The elimination half-lives for these patients are derived from the mean terminal elimination rate constants (Kel): 0.185/hr (newborn to 2 months old), 0.256/hr (2 to <6 months old), 0.299/hr (6 months to <1 year), 0.322/hr (1 to <2 years), and 0.307/hr (2 to <12 years old). The adult mean terminal elimination rate constant is 0.336/hr.
The actual VISIPAQUE clearance and volume of distribution in paediatric patients were not determined. Pharmacodynamic dose adjustments to account for differences in elimination halflife in paediatric patients under 6 months of age have not been studied.
No long-term animal studies have been performed to evaluate the carcinogenic potential of VISIPAQUE.
VISIPAQUE did not induce gene mutation in bacteria or Chinese hamster ovary (CHO) cells in vitro. It was not clastogenic in CHO cells in vitro or in mice in vivo.
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