Iodinated Contrast Media for Oral Use Low-osmolar Non-ionic Iohexol GE Title or job number 7/18/2012 Many Examples of Use of Contrast Media in Imaging Cardioangiography CT enhancement Urography Cerebral angiography VenographyJ Peripheral angiography Radiographic Imaging of the GI Tract: Use of Oral Contrast media (CM) X-ray Examinations Conventional (Plain Film) Fluoroscopy - CM IV Fluoroscopy + CM Oral CT + CM CT - CM IV Types of Oral Positive CM LOCM HOCM BARIUM HOCM, High-Osmolar Contrast Media LOCM, Low-Osmolar Contrast Media Types of Commercially Available Oral Positive C  Barium sulfate suspensions  Many preparations available  Water soluble  High-Osmolar Contrast Media: diatrizoate preparations  Low-Osmolar Contrast Media: iohexol Freeman A Textbook of Contrast Media 1999:135-148 Ott DJ et al JAMA 1983;249:2380-2384 Differing Osmolalities Osmolality ranges of different contrast media at 37°C in relation to blood (mOsm/kgH 2O) at most commonly used concentrations 2130+ 1870 Iodixanol, at all iodine concentrations is the only contrast medium available for intravascular use with osmolality equal to blood 915 521 290 290 Blood Visipaque LOCM HOCM Advantages and Disadvantages of Current Oral CM Properties of an Ideal Oral CM  Safe - Low risk if aspirated or leaked into the peritoneum  Tolerable - Low GI side effects   Palatable - Acceptable taste Low viscosity - Easy to swallow  Effective - Provides adequate contrast delineation  Water soluble - Uniform distribution  Fluid enough to pass through narrow areas Seltzer SE et al CRC Crit Rev Diagn Imaging 1979;12:77-99 Barium Sulphate Advantages: Historically a preferred agent for opacification of the GI tract  Dense  Not absorbed from the GI tract  Usually safe  Readily available  May be less expensive  Cohen MD Radiology 1987;162:447-456 Freeman A Textbook of Contrast Media 1999:135-148 Barium Sulphate Disadvantages:   Physical instability Contraindicated if there is a suspected perforation   Can be fatal if aspirated  Bitter taste, chalky Difficult to swallow large volumes Freeman A Textbook of Contrast Media 1999:135-148 Highlights of Clinical Studies The taste of iohexol has been favorably accepted in pediatric patients Iohexol is well-suited for use in infants, children, and elderly patients Iohexol is a good alternative to diatrizoate in terms of radiographic density In patients where barium is contraindicated, iohexol is an alternative Stordahl A Acta Radiol 1980; 29:53-56 Conclusions   Use of LOCM is recommended for oral use Iohexol produces good visualization of the GI tract and well-tolerated and readily absorbed if leaked into the peritoneal cavity  Taste of iohexol has been favorably accepted by both adult and pediatric patients Iohexol is the only LOCM/Non-Ionic Monomer approved by the FDA for oral use LOCM, Low-Osmolar CM Medical points: Long track record of usage and safety - over 25 years/450 million doses All age groups: neonates to elderly All indications Thank you Back-up Foundation of Omnipaque Landmark Clinical Trials - Unsurpassed Clinical Efficacy Establishe Large scale trials Schrott et al 1986: 50,642 patients Omnipaque resulted in a low rate of adverse events (2.1%) in patients undergoing intravenous urography Langer et al 1987: 4,970 patients Omnipaque resulted in a low rate of adverse events (1.6%) in patients undergoing CT Levorstadt et al 1989: 5,339 patients Omnipaque resulted in a significantly lower rate of adverse events than ionic contrast media in patients undergoing coronary angiography Wolf et al 1991: 14,863 patients Omnipaque was significantly safer than ionic contrast media in patients undergoing CT or urography Rudnick et al 1995: 1,196 patients Omnipaque is less nephrotoxic than diatrizoate in patients undergoing cardiac catheterization 43 This is GE Healthcare 2011 Summary of most recent iohexol studies Study Comparators Indication Result McNamara AJR 2010 Gastroview (diatrizoate sodium) Gomi Eur Rad 2009 iomeprol 300, iopamidol 300, iopromide 300, ioversol 320 CT • Significantly higher acute AE’s in iomeprol & iopromide LaBounty study 2012 iopamidol ioversol Invasive cardiac catheterisatio n procedures • no significant differences for haemodialysis rates or inhospital mortality Dillman Study 2012 Iopamidol 300 CT • No clinical difference observed • Both agents can be used with confidence +PLUSPAK v glass, lifecycle Glass bottles All • Using +PLUSPAK instead of glass saves hospitals money4 Oral • Patients preferred taste of AbdominalOmnipaque pelvic CT • No difference in image quality • Similar rates of AE’s evaluation 2012 VERSUS LOCM The balance of evidence • The balance of evidence shows that Omnipaque has not been surpassed by other LOCM for either diagnostic efficacy or tolerability Comparator Iopamidol iomeprol iopromide iobitridol ioversol Procedure Number of patients Superior efficacy to Omnipaque* Superior safety to Omnipaque myelography1 n=363 no no paediatric cardiac angiography2 n=62 no no intravenous urography3 n=60 no no myelography4 n=83 no no aortography + visceral angiography5 n=125 no no excretory urography6 n=200 no no CT of the head7 n=276 no no hepatic CT8 n=146 no no intravenous urography9 n=80 no no peripheral + visceral n=60 no no arteriography10 lower limb phlebography11 n=120 angiography12 n=80 no ioxaglate no no no *e.g opacification, image quality, ability to make a diagnosis Omnipaque versus LOCM Surveillance studies (Gomi et al) • In a prospective, randomised study of 8,931 consecutive patients undergoing contrastenhanced CT at the Toho University Ohashi Medical Centre in Japan, a significantly higher incidence of acute adverse reactions was found for iomeprol and iopromide than for Omnipaque VERSUS HOCM Problems of high osmolality • High osmolality is associated with various toxic effects including pain, blood-brain barrier disruption, vagal/emetic centre stimulation, decreased myocardial contractility, reduced fibrillation threshold and contrast induced nephropathy (CIN) - such osmotoxicity provided the impetus for the development of LOCM VERSUS HOCM Decline in HOCM usage • With their superior tolerability profile, LOCM have largely replaced HOCM in most countries VERSUS HOCM Fewer adverse events than than HOCM - IV In body CT • Omnipaque: 2/3 of the rate of comparator HOCM VERSUS HOCM Fewer adverse events than HOCM - IA Reduced incidence of adverse events with Omnipaque vs diatrizoate VERSUS HOCM Sufficiently well tolerated for myelography • Unlike HOCM, Omnipaque is sufficiently well tolerated to be indicated for myelography - so much so that the incidence and severity of adverse events was significantly lower with Omnipaque than with another LOCM (iopamidol) Incidence of side effects after myelography with Omnipaque and iopamidol VERSUS HOCM More acceptable to patients than HOCM • Less nausea, vomiting, heat sensation, pain and discomfort - side effects that potentially degrade image quality ... Omnipaque package insert; Ultravist package insert; Isovue package insert; Optiray package insert Administration of Oral Contrast Media Diluting Omnipaque Dilute oral plus i.v Omnipaque: • Useful... 6-9 mgI/mL administered orally in conjunction with i.v Omnipaque 300 is indicated in adults for use in CT the abdomen Omnipaque 350 (350 mg I/mL) 25 mL to final liter Omnipaque 350 mgI/mL is... Comparing Omnipaque with the standard oral contrast used Diatrizoate sodium for CT body :  Patient preference for oral contrast  Bowel opacification   McNamara et al Study methods The Omnipaque