XENETIX AND COMPETITORS
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
Iodixanol 270 290 5.8
Iodixanol 320 290 11.4
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
PHYSICO-CHEMICAL FEATURES
10.5820Iohexol 350
5.7690Iohexol 300
3.2520Iohexol 240
Viscosity (mPa.s) at 37°C
Osmolality(mOsm/kg water)
Preparation
OMNIPAQUE
PHYSICO-CHEMICAL FEATURES
10.5820Iohexol 350
5.7690Iohexol 300
3.2520Iohexol 240
Viscosity (mPa.s) at 37°C
Osmolality(mOsm/kg water)
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
COUNTER-ARGUMENTATION
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
PHYSICO-CHEMICAL FEATURES
IOPAMIRON
9.5799Iopamidol 370
4.5616Iopamidol 300
3.0515Iopamidol 250
2.0413Iopamidol 200
Viscosity (mPa.s) at 37°C
Osmolality(mOsm/kg water)
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
COUNTER-ARGUMENTATION
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
COUNTER-ARGUMENTATION (continued)
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
PHYSICO-CHEMICAL FEATURES
ULTRAVIST
9.5770Iopromid 370
4.6610Iopromid 300
2.8480Iopromid 240
1.5340Iopromid 150
Viscosity (mPa.s) at 37°C
Osmolality(mOsm/kg water)
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
COUNTER-ARGUMENTATION
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
COUNTER-ARGUMENTATION (continued)
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
PHYSICO-CHEMICAL FEATURES
IOMERON
12.6726Iomeprol 400
7.5618Iomeprol 350
4.5521Iomeprol 300
2.9435Iomeprol 250
1.4301Iomeprol 150
Viscosity (mPa.s) at 37°C
Osmolality(mOsm/kg water)
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
ARGUMENTATION (continued)
High Iomeprol chemical stability allows not to use the EDTA stabilizator
High Iomeprol hydrophilicity allows a high concentrated product: 400 mgI/ml
IOMERON
COUNTER-ARGUMENTATION
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
COUNTER-ARGUMENTATION (continued)
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
COUNTER-ARGUMENTATION (continued)
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
PHYSICO-CHEMICAL FEATURES
IVEPAQUE
12.0810Iopentol 350
6.5640Iopentol 300
3.9520Iopentol 250
2.8410Iopentol 200
1.7310Iopentol 150
Viscosity (mPa.s) at 37°C
Osmolality(mOsm/kg water)
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
COUNTER-ARGUMENTATION
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
COUNTER-ARGUMENTATION (continued)
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
PHYSICO-CHEMICAL FEATURES
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
ARGUMENTATION (continued)
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
COUNTER-ARGUMENTATION
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
COUNTER-ARGUMENTATION (continued)
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
PHYSICO-CHEMICAL FEATURES
XENETIX
10915Iobitridol 350
6695Iobitridol 300
4585Iobitridol 250
Viscosity (mPa.s) at 37°C
Osmolality(mOsm/kg water)
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
ARGUMENTATION (continued)
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
COUNTER-ARGUMENTATION
No clinical significative advantages compared to nonionics already available
No myelography, which in non open minded radiologists, could mean lower neurological safety
XENETIX