Xenetix vs Competition

XENETIX AND COMPETITORS

VISIPAQUE

I

I

I

CH2CHCH2NHCO

OH

OH

CH2CHCH2NHCO

OHOH

COCH3

I

I

I

NOH2CHCH2N

CH3

CO

OHOH

CONHCH2CHCH2

CONHCH2CHCH2

OH

OH

OH

ACTIVE INGREDIENT

Iodixanol - Nycomed ( Norway)

CHEMICAL STRUCTURE

PHYSICO-CHEMICAL FEATURES

VISIPAQUE

PreparationPreparation OsmolalityOsmolality(mOsm/kg water)(mOsm/kg water)

Viscosity (mPa.s) at Viscosity (mPa.s) at 37°C37°C

Iodixanol 150 290 1.7



PROCEDURES

VISIPAQUE

Cardiac angiography

Phlebography

IVU

Peripheral arteriography

Peripheral IA DSA

Cerebral IA DSA

Computed tomography (head - whole body)

Iodixanol 320Iodixanol 270Iodixanol 150Indications

PRESENTATIONS

VISIPAQUE

Visipaque 320

Visipaque 270

Visipaque 150

200 ml100 ml75 ml50 ml20 ml

ARGUMENTATION

VISIPAQUE

An isotonic solution provides comfort for the patient during the examination (by reducing pain and heat) and security of examination for theradiologist (more reliable diagnosis because of optimal contrast due to a reduction of artefacts related to patient movements)The addition of Na+ and Ca++ stabilises physiological functions, especially cardiac, leading to a decreased risk of arrythmia and ventricular fibrillation

COUNTER-ARGUMENTATION

VISIPAQUE

Like any non-ionic dimer, Visipaque is very viscous and its transit time in the microcirculation is therefore prolonged, leading to a risk of vascular ischaemia and prolongation of the endothelium contact time.Due to its iso-osmolality, there is no osmotic diuresis phenomenon; the contact time with renal cells is increased, with a consequently increased risk of renal toxicity.

COUNTER-ARGUMENTATION (continued)

VISIPAQUE

The combination of iso-osmolality/high viscosity also increases the viscosity of the urine and causes resistance to urine flow in the distal convoluted tubule.Due to the high viscosity of Visipaque, manual injections are more difficult and require preheating of the product, leading to practical limitations in certain indications

ACTIVE INGREDIENT

Iohexol - Nycomed ( Norway)

CHEMICAL STRUCTURE

I

I

I

CONHCH2CHOHCH2OH

N CONHCH2CHOHCH2OH

CH3OC

CH2

CHOH

CH2OH

OMNIPAQUE


10.5820Iohexol 350

5.7690Iohexol 300

3.2520Iohexol 240

Viscosity (mPa.s) at 37°C

Osmolality(mOsm/kg water)

Preparation

OMNIPAQUE


10.5820Iohexol 350

5.7690Iohexol 300

3.2520Iohexol 240



Preparation

OMNIPAQUE

PROCEDURES

OMNIPAQUE

Arthrography

DSA (iv)

DSA (ia)

Angiocardiography

Phlebography

Arteriography

Urography

Iohexol 350Iohexol 300Iohexol 240Indications

PRESENTATIONS

OMNIPAQUE

Iohexol 350

Iohexol 300

Iohexol 240

50ml 75ml 500ml200ml100ml20ml10ml

ARGUMENTATION

The Based on Nycomed’s fame with its worldwide sold iohexol.

Due Key points : high level of hydrophilicity low protein-binding rate

Simple USP « Believe in experience »

Nycomed well-known for its high level ofservices policy

OMNIPAQUE


Elimination half-life higher compared toXenetix (2-3 hr vs 1.8 hr)

Preclinical studies favourable to Xenetix(kidney - neurology)

OMNIPAQUE

ACTIVE INGREDIENT

Iopamidol - Bracco (Italy)

CHEMICAL STRUCTURE

IOPAMIRON

I

I

I

CONHCH

CONHCHCH3CHCOHN

OH

CH2OH

CH2OH

CH2OH

CH2OH


IOPAMIRON

9.5799Iopamidol 370

4.5616Iopamidol 300

3.0515Iopamidol 250

2.0413Iopamidol 200



Preparation

PROCEDURES

IOPAMIRON

Radiculography

Phlebography

Myelography

DSA (iv, ia)

IVU

CT

Angiocardiography

Arteriography

Iopamidol 300

Iopamidol 370

Iopamidol 250

Iopamidol 200

Indications

PRESENTATIONS

IOPAMIRON

Iopamidol 370

Iopamidol 300

Iopamidol 250

Iopamidol 200

75ml 100ml20ml 30ml 500ml200ml50ml10ml5ml

ARGUMENTATION

Confidence through experience. More than 2500 scientific publications since 1980 confirm

the high safety level of the compound.

Very low neurotoxicity level: high LD50

Authorization for use in children and myelography confirm good safety profile

IOPAMIRON


Not an optimal ICM: iopamidol 370 may crystallize (indicated in the patient information leaflet)

Iopamidol comprises only five OH radicals lower hydrophilicity compared to Xenetix

Elimination half-life: 2 hours (more than Xenetix)

IOPAMIRON


Image of an old fashioned ICM with the launch of Iomeron

No particular customer-oriented service 500 ml is only available in the 300 concentration

IOPAMIRON

ACTIVE INGREDIENT

Iopromid - Schering (Germany)

CHEMICAL STRUCTURE

ULTRAVIST

I

I

I

CONCH2CHOHCH2OH

CONHCH2CHOHCH2OHCH2COHN

O

CH3

CH3


ULTRAVIST

9.5770Iopromid 370

4.6610Iopromid 300

2.8480Iopromid 240

1.5340Iopromid 150



Preparation

PROCEDURES

ULTRAVIST

Phlebography

Arteriography

Peripheric angiography

Angiography

Angiocardiography

Iopromid 300 Iopromid 370Iopromid 240Iopromid 150Indications

PRESENTATIONS

ULTRAVIST

Iopromid 370

Iopromid 300

Iopromid 240

Iopromid 150

150ml75ml 100ml20ml 30ml 500ml200ml50ml10ml5ml

ARGUMENTATION

Communication policy based on Schering’s company fame. Iopromid is available till the middle of the 80’s: explained by the USP « proven is proven »

Positioning according mainly to image quality and tolerance in the main indications (ia and iv)

All communication is focused on the « core » of iopromid (physicochemical features,

osmolality, viscosity) but neither on the environment of it

ULTRAVIST

ARGUMENTATION (continued)

Tolerance in cardiology mainly explained by low osmolality

Low protein-binding-rate is the unique documented feature

Active positioning of the range is iopromid 370 in cardiology, iopromid 300 in DSA and CT

and iopromid 240 in phlebography

ULTRAVIST


Not Iopromid physicochemical features are not optimal:

very poor hydrophilicity (four OH only) very high level for crossing the placenta: 5-10% (<0.1% for Xenetix)

Therefore, no quantitative data available regarding the half-life elimination

ULTRAVIST


Potential adverse events higher for Iopromid, although no clinical data available today for confirming this point

Main advantage for Xenetix: service policy around the product

ULTRAVIST

ACTIVE INGREDIENT

Iomeprol - Bracco (Italy)Iomeprol - Bracco (Italy)

CHEMICAL STRUCTURE

IOMERON

I

I

I

CONHCH2CHCH2OH

CONHCH2CHCH2OHN

OH

CH3

HOCH2CO

OH


IOMERON

12.6726Iomeprol 400

7.5618Iomeprol 350

4.5521Iomeprol 300

2.9435Iomeprol 250

1.4301Iomeprol 150



Preparation

PROCEDURES

IOMERON

CT head

DSA phlebograhy

Phlebography

Infusion urography

IV urography

Iomeprol 350

Iomeprol 300

Iomeprol 400

Iomeprol 250

Iomeprol 150Indications

PROCEDURES (continued)

IOMERON

Angiocardiography

Abdomen

Thorax

Cerebral IA DSA

Angiography

CT total body

Iomeprol 350

Iomeprol 300

Iomeprol 400

Iomeprol 250

Iomeprol 150Indications

PRESENTATIONS

IOMERON

Iomeprol 400

Iomeprol 350

Iomeprol 300

Iomeprol 250

Iomeprol 150

50ml 75ml 500ml200ml100ml30ml10ml

ARGUMENTATION

Lowest viscosity among all non-ionics available today with following advantages:

easy handling when filling the syringes easier injection in tight catheters

Lowest osmolality among all non-ionics available today for: improved tolerance improved imaging due to reduced moving

artefacts

IOMERON


High Iomeprol chemical stability allows not to use the EDTA stabilizator

High Iomeprol hydrophilicity allows a high concentrated product: 400 mgI/ml

IOMERON


For every contrast agent, there is a close relationship between osmolality, viscosity and hydrophilicity

Iomeprol possesses the lowest osmolality and viscosity, but displays a very poor hydrophilicity

(octanol/water partition coefficient)

Quantitatively confirmed (only five OH groups)

IOMERON


What is the interest in very low features if counterbalanced by such a chimiotoxicity?

Iomeprol possesses the same chemical formula as Iopamidol: crystallization risks are well-

known for Iopamidol 370. What about Iomeprol 400?

Today, the trend is to reduce the concentration used

IOMERON


Iomeprol has a poor solubility (126% vs 140% for Xenetix)

The absence of stabilizator is not due to the product stability. EDTA binds to cupfer elements which are mainly due to the production process (involving metallic materials). Since Iomeprol is produced in non-metallic material, this risk does not exist

During clinical trials for registration, Iomeprol has only be compared to diatrizoate and Iopamiron (non comparison with Omnipaque)

IOMERON

ACTIVE INGREDIENT

Iopentol - Nycomed (Norway)

CHEMICAL STRUCTURE

IVEPAQUE

I

I

I

CONHCH2CHOH

CONHCH2CHOH

CH3

HOCH2

CH2OH

CH2OH

CH3OHCCH2N

O=C


IVEPAQUE

12.0810Iopentol 350

6.5640Iopentol 300

3.9520Iopentol 250

2.8410Iopentol 200

1.7310Iopentol 150



Preparation

PROCEDURES

IVEPAQUE

CT

Angiocardiography

Arteriography

Iopentol 300

Iopentol 250

Iopentol 350Iopentol 200

Iopentol 150Indications

PRESENTATIONS

IVEPAQUE

Iopentol 350

Iopentol 300

Iopentol 250

Iopentol 200

Iopentol 150

50ml (US

packs)

75ml 200ml175ml100ml50ml20ml

ARGUMENTATION

2 main arguments developed by Nycomed regarding:

PHYSICOCHEMICAL FEATURES:PHYSICOCHEMICAL FEATURES: improved endothelium safety good renal safety no effect on blood-brain-barrier

CUSTOMER-ORIENTED SERVICECUSTOMER-ORIENTED SERVICE unique soft pack

Nycomed « In Out » system (recycling system)

IVEPAQUE


Iopentol represents the worst compromise regarding physicochemical features of all non-ionic compounds available today: high viscosity, average osmolality and poor hydrophilicity

Renal safety profile is only measured by the enzyme elimination although it is well-known that this measurement is not clinically relevant. Today, the gold standard is creatininemia (as with Xenetix)

IVEPAQUE


Iopentol does not exist in 500 ml presentation

The unique soft pack is available for 50 ml presentation: feedback from the field report that the opening remains inconvenient

With Iodixanol, Iohexol and Iopentol, Nycomed has at least 3 products on the market. With regard to its positioning, this matter of fact does not serve to strengthen the Company’s message

IVEPAQUE

ACTIVE INGREDIENT

Ioversol - Mallinckrodt (USA)

CHEMICAL STRUCTURE

OPTIRAY

I

I

I

CONHCH2CHCH2OH

N CONHCH2CHCH2OH

HOCH2CO

OH

OH

HOCH2CH2


OPTIRAY

8.3790Ioversol 350

6.1710Ioversol 320

5.0630Ioversol 300

3.1500Ioversol 240

1.6350Ioversol 160

Viscosity (mPa.s) at Viscosity (mPa.s) at 37°C37°C

OsmolalityOsmolality(mOsm/kg water)(mOsm/kg water)

PreparationPreparation

PROCEDURES

OPTIRAY

Ventriculography

Phlebography

IVU

DSA

CT

Coronarography

Aortography

Arteriography

Ioversol 320

Ioversol 300

Ioversol 350

Ioversol 240

Ioversol 160

Indications

PRESENTATIONS

OPTIRAY

IPFS

IPFS

IPFS

Ioversol 350

IPFS

PSF/ IPFS

Ioversol 320

IPFS

IPFSPFS

PSF/ IPFS

PFS

Ioversol 300

Ioversol 240

Ioversol 160

150ml100ml 125ml30ml 50ml 500ml200ml75ml20ml10ml

ARGUMENTATION

Close relationship between hydrophilicity and overall safety (tolerance, comfort)

Ioversol comprises six OH radicals and is marketed according to the « balanced hydrophilicity » concept

OPTIRAY


PFS in order to: cut down examination cost allow easier handling minimize risk of misunderstanding the product

Mallinkcrodt sells CT injector and is able topropose a global approach to its customers

OPTIRAY


With the concept of stabilized hydrophilicity, Xenetix is one step forward

This is confirmed by an improved solubility (140% for Xenetix, 120% for Optiray) and the elimination

half-life (1.8 hr for Xenetix, 2.06 for Optiray)

This feature is very important for renal safety, especially for patients at risk. With Xenetix, contact

time with celles is shorter than with Ioversol

OPTIRAY


Poor dose-range, PFS not necessarily well adapted to CT indications since more than 120 ml is often needed for this type of examination

Less flexibility if a second shot is necessary

Xenetix provides the right solution for the risk of mistake with flag label as well as additional batch number and expiry date information

Xenetix is available in 500ml presentation at 3 concentrations

OPTIRAY

ACTIVE INGREDIENT

Iobitridol - Guerbet (France)

CHEMICAL STRUCTURE

XENETIX

I

I

I

NH-C-CH

CH2OH-CHOH-CH2-N-CO

O

CH3

CO-N-CH2-CHOH-CH2OH

CH3


XENETIX

10915Iobitridol 350

6695Iobitridol 300

4585Iobitridol 250



Preparation

PROCEDURES

XENETIX

- cranial

- whole body

DSA (ia)

DSA (iv)

CT :

Iobitridol 300 Iobitridol 350Iobitridol 250Indications

PROCEDURES (continued)

XENETIX

- peripheral

- cerebral

Iobitridol 300

Arteriography

CT chest

Urography

Iobitridol 350Iobitridol 250Indications

PRESENTATIONS

XENETIX

60ml*

75ml*

Iobitridol 350

Iobitridol 300

Iobitridol 250

500ml*200ml100ml 50ml20ml

* according to the country

ARGUMENTATION

Xenetix is the achievement of an original chemical concept: the stabilized hydrophilicity

The highest hydrophilicity profile among all product marketed today (osmotic coefficient )

The most balanced compromise, benefit for the patient/advantage for the radiologist

Significative tolerance advantages proved on preclinical studies (renal safety - neurological safety) in comparison with Omnipaque

XENETIX


The quickest elimination half-life (1.8h)

Important added value to the customer with services policy associated with Xenetix (flag label, filling kit, 500 ml presentation in all concentrations)

XENETIX


No clinical significative advantages compared to nonionics already available

No myelography, which in non open minded radiologists, could mean lower neurological safety

XENETIX

Documents

Xenetix vs Competition