OMNIPAQUE oral use vietnam

Types of Commercially Available Oral Positive CM Water soluble  High-Osmolar Contrast Media: diatrizoate preparations  Low-Osmolar Contrast Media: iohexol Freeman A.. Oral HOCM Ionic-

Iodinated Contrast Media for Oral Use Low-osmolar Non-ionic Iohexol

1

GE Title or job number

7/18/2012

Many Examples of

Use of Contrast Media in

Imaging

Cardioangiography

Cerebralangiography

CT enhancement

VenographyJ

Urography

Peripheralangiography

Radiographic Imaging of the

GI Tract: Use of Oral Contrast media (CM)

X-ray Examinations

Types of Oral Positive CM

Types of Commercially Available Oral Positive CM

 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 2 O) at most commonly used concentrations

2130+ 1870

Iodixanol, at all iodine concentrations is the only contrast medium available for intravascular use with osmolality equal

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

 Effective - Provides adequate contrast delineation

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

 Can be fatal if aspirated

 Bitter taste, chalky

 Difficult to swallow large volumes

Freeman A Textbook of Contrast Media 1999:135-148.

Oral HOCM (Ionic-Monomers)

Advantages:

 Water soluble (ie, solutions, not suspensions)

 Readily absorbed by peritoneum if leaked from the GI tract

 Pass through small bowel rapidly

 Can be diluted to desired concentration

HOCM, High-Osmolar CM Cohen MD Radiology 1987;162:447-456.

Freeman A Textbook of Contrast Media 1999:135-148.

Oral HOCM (Ionic-Monomers)

Disadvantages:

 Poor visualization of distal GI tract

 Possible toxicity to bowel mucosa

 Possible fluid shifts and

dehydration- due to high osmolarity

 Adverse events if aspirated

 Some patients may have sensitivity to iodinated contrast

HOCM, High-Osmolar CM Cohen MD Radiology 1987;162:447-456.

Freeman A Textbook of Contrast Media 1999:135-148.

 Can cause mild-to-severe GI distress (eg, diarrhea, nausea, vomiting, cramps)

Oral LOCM (Non-Ionic Monomers)

Advantages:

 Well-accepted by patients due to

neutral taste *

 Rapidly absorbed from the peritoneum

 Rapidly dissipated from the lungs if

aspirated

 Can be used where barium is contraindicated or not tolerated

CT colonography tagging 88 y/o female

LOCM, Low-Osmolar CM Cohen MD Radiology 1987;162:447-456; Omnipaque package insert Smevik B, et al Contrast Media in Pediatric Radiology 1987:79-80 *

Oral LOCM (Non-Ionic Monomers)

Disadvantages :

 Lower attenuation of X-rays than barium (Fluoroscopy)

 Possible GI discomfort (eg,diarrhea, nausea, vomiting)

 Some patients may have sensitivity to iodinated contrast

LOCM, Low-Osmolar CM Cohen MD Radiology 1987;162:447-456; Omnipaque package insert Smevik B, et al Contrast Media in Pediatric Radiology 1987:79-80 *

Indications and Guidelines for Iodinated Contrast

 Administration before bowel surgery

 Administration before endoscopy

 As a bowel marker for percutaneous CT-guided interventional procedures

 Iohexol (Omnipaque) is the only LOCM approved by the FDA for oral use

LOCM, Low-Osmolar CM American College of Radiology Manual of Contrast Media Version 5.0;

http://www.fda.gov/cder/foi/appletter/2002/18956slr039ltr.pdf;

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:

between normal loops of the bowel and adjacent organs or areas of

suspected pathology

conjunction with i.v Omnipaque 300 is indicated in adults for use in CT of the abdomen.

Omnipaque 350

Omnipaque 350 mgI/mL is indicated in adults for use in oral pass thru examination of the GI tract.

ORAL USE

The importance of taste

• Bowel opacification is predominantly a function of volume of contrast consumed and time elapsed to scanning

• If a contrast medium for oral use is not unpleasant to taste, patients are more likely to be able to drink the volume required - not to

mention feel satisfied with the radiology experience

ORAL USE

• Hypertonic agents draw fluid from the plasma and interstitium into the bowel,resulting in progressive loss of radiocontrast through dilution as the agenttravels through the gut

- Omnipaque provided better contrast density than sodium diatrizoate inadults with suspected intestinal obstruction

- Omnipaque is well suited for visualisation of intestinal loops and providedgood quality scans in children of all ages

- Omnipaque was well tolerated in a range of patients of various ages posingmajor management problems

Clinical comparison : Omnipaque ( iohexol ) with other iodinated

contrast media

Lönnemark et al Study:

Oral contrast media in CT of the abdomen Iohexol of different concentrations as

a gastrointestinal contrast medium.

 Aim: a double blind randomised study to compare 3 different concentrations of

Omnipaque when given orally (by mouth) to adults for bowel opacification in abdominal CT.

 Method: Omnipaque 350 was diluted in water 78-fold, 52-fold and 39-fold respectively to

obtain final concentrations of 4.5, 6.75 and 9 mgI/ml A total of 30 patients were given

800mL of diluted contrast to drink; each concentration was given to 10 patients Patients were asked to grade the taste of Omnipaque on a scale between 0 ("awful") and 100 ("good taste" or no problem to drink").

 Results: No significant differences between the 3 Omnipaque concentrations were found

regarding enhancement, distribution or patient tolerability The mean tolerability scores ranged from 60-75 Texture had mean score ranging from 75-86 on the same scale.

When using Omnipaque as a bowel CM for CT the concentration of 4.5 mgI/ml was sufficient for bowel opacification In addition, these patients would repeat the procedure with oral Omnipaque if required.

Acta Radiol 1995; 36(4):396-398.

retrospectively assessed for radiographic quality and clinical findings, and compared with

operative findings and clinical outcomes.

 Results: Obstruction was diagnosed in 12 patients, of whom 7 proceeded to surgery

(which confirmed the radiological diagnosis) Fistulae were found in 11 patients, of which 8

went to surgery (which confirmed the radiological diagnosis) 5 patients whose X-ray

excluded obstruction or fistulae went to surgery and in none of these patients was either obstruction or fistula found - thus demonstrating the accuracy of the radiological

procedure.

 The authors emphasise that non-ionic CM are particularly valuable in clinically complex patients with major management problems, e.g where there is doubt about the site, possible perforation or impending surgery.

Eur Radiol 1999; 9(4):706-710.

Diederichs et al Study:

Oral administration of intravenous contrast media: a tasty alternative to conventional oral contrast media in computed tomography

 Aim:

Since many oral CM have a strong metallic taste, this study attempted

to identify CM with a better or neutral taste, whilst still achievingoptimal image quality

 Results:

There were no significant differences in radiographic enhancement between the CM.

Rofo 2007; 179(10):1061-1067.

Smevik et al Study Iohexol for contrast enhancement of bowel in pediatric abdominal CT

Aim: This study in children examined the tolerability of oral diluted Omnipaque and the quality

of the images obtained.

Method: Abdominal CT scans from 160 paediatric bowel examinations with Omnipaque, at a

concentration of 6-7 mgI/ml were evaluated retrospectively Over 80% of the patients had an oncological (cancer) diagnosis.

Omnipaque was diluted with a drink of the patient's choice The dilution was 1ml

Omnipaque in 50ml of water, juice, lemonade or milk In this mixture, the taste of

Omnipaque itself was undetectable.

139 out of 142 children drank the full volume of dilute Omnipaque The remaining patients received Omnipaque rectally.

Oral Omnipaque is well-tolerated in paediatric age-group

Acta Radiol 1990; 31(6):601-604.

Smevik et al Study Iohexol for contrast enhancement of bowel in pediatric abdominal CT

• Young patients can often be reluctant to undergo examinations - they cannot be

persuaded to co-operate in the same way that an adult can

• They find the bitter taste of high osmolar contrast media such as diatrizoate

Stordahl et al Study

Water-soluble contrast media in radiography of small bowel

obstruction Comparison of ionic and non-ionic contrast media

 Aim: To compare hyperosmolar Gastrografin 370 mgI/ml to osmolar Omnipaque 350 mgI/ml in patients referred for enteric follow-

low-through examinations for possible GI obstruction

 Method: This double-blind, parallel group study assessed 50 adult

patients referred for the procedure who all received 100m l of eitheragent, which was allocated randomly Image quality and adverseevents were assessed

 Results: Omnipaque gave a statistically significantly higher density than Gastrografin both at 1 hour (p=0.007) and 4 hours (p=0.04) after

ingestion Though Omnipaque was also better than Gastrografin

regarding taste, nausea, vomiting or diarrhoea , although differences

were not statistically significant

Acta Radiol 1988; 29(1):53-56.

 McNamara et al:

 Published AJR Nov 2010

 Double-blinded study of 300 patients

 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 concentration used is 9g per liter so they diluted 26ml of 350mg/Omnipaque with 974ml of water

 In the first part: patients were randomised to either,

drinking 900ml of one product and then had CT scan.

 In the second part, all patients had 30ml of each product ( blinded) and were asked directly which they preferred.

 During the clinical phase ( 1st part ) There was no

significant difference in bowel opacification or adverse effect profile for the CT study.

McNamara et al Results:

Adult body CT patients gave Omnipaque a significantly better taste preference score than they gave diatrizoate sodium

 Peterson et al: published March 2011, J Comput Assist Tomogr

 Also double-blinded study but smaller, study group was

100 patients

 Half randomised to either product : Iohexol vs Diatrizoate

Peterson et al Study method

 Omnipaque concentration was 8g per liter so they diluted 23ml of 350mg/Omnipaque to 977 ml of water

 After the CT study patients were asked to rate the taste of the contrast on a scale of 1 to 10 and asked about possible AEs or minor symptoms

 Opacification of the ileum was better with iohexol This was attributed possibly to less osmotic drag by iohexol causing less dilution of the contrast agent

 There was no statistically significant difference between the 2 agents in adverse effects.

How about swallow studies ?

 Contrast media osmolality is ofparticular importance in

neonates and small children

 These patients are thought to beespecially susceptible to fluidshifts and have a lower

tolerance for intravascular (IV)osmotic loads when compared

to adults

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

well-tolerated and readily absorbed if leaked into the

peritoneal cavity

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:

1 Long track record of usage and safety - over 25

years/450 million doses

2 All age groups: neonates to elderly

3 All indications

Thank you

Back-up

Foundation of Omnipaque

Landmark Clinical Trials - Unsurpassed Clinical Efficacy Established

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

McNamara AJR Gastroview (diatrizoate

• Similar rates of AE’s.

iopromide 300, ioversol 320

LaBounty study iopamidol Invasive • no significant differences for

in-catheterisatio hospital mortality

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 Procedure Number of Superior efficacy Superior safety

patients to Omnipaque* to Omnipaque

Omnipaque versus LOCM

Surveillance studies (Gomi et al)

contrast-enhanced 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 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