Ablavar

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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1. NAME OF THE MEDICINAL PRODUCT  
 
Ablavar 0.25 mmol/ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
1 ml Ablavar solution for injection contains 244 mg (0.25 mmol) gadofosveset trisodium equivalent to 
227 mg gadofosveset. 
 
 
Each vial of 10 ml solution contains a total of 2.44 g (2.50 mmol) of gadofosveset trisodium 
equivalent to 2.27 g of gadofosveset 
Each vial of 15 ml solution contains a total of 3.66 g (3.75 mmol) of gadofosveset trisodium 
equivalent to 3.41g of gadofosveset. 
Each vial of 20 ml solution contains a total of 4.88 g (5.00 mmol) of gadofosveset trisodium 
equivalent to 4.54g of gadofosveset. 
 
 
Excipient 
This medicinal product contains 6.3 mmol sodium (or 145 mg) per dose. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM  
 
Solution for injection. 
Clear, colourless to pale yellow liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
This medicinal product is for diagnostic use only. 
Ablavar is indicated for contrast-enhanced magnetic resonance angiography (CE-MRA) for 
visualisation of abdominal or limb vessels in adults only, with suspected or known vascular disease. 
 
4.2 Posology and method of administration  
 
This medicinal product should only be used by physicians experienced in the field of diagnostic 
imaging. 
 
Posology 
Adults: 0.12 ml/kg body weight (equivalent to 0.03 mmol/kg) 
 
Imaging time points 
Dynamic imaging begins immediately upon injection. Steady state imaging can begin after the 
dynamic scan has been completed. In clinical trials, imaging was completed up to approximately one 
hour following injection. 
 
No clinical information is available about repeated use of this medicinal product. 
 
Special populations 
 
Elderly (aged 65 years and above) 

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No dose adjustment is considered necessary. Caution should be exercised in elderly patients (see 
section 4.4). 
 
Renal impairment 
Use of Ablavar should be avoided in patients with severe renal impairment 
(GFR < 30 ml/min/1.73 m2) and in patients in the perioperative liver transplantation period unless the 
diagnostic information is essential and not available with non-contrast enhanced magnetic resonance 
imaging (MRI) (see section 4.4). If use of Ablavar cannot be avoided, the dose should not exceed 
0.03 mmol/kg body weight. More than one dose should not be used during a scan. Because of the lack 
of information on repeated administration, Ablavar injections should not be repeated unless the 
interval between injections is at least 7 days. 
 
Hepatic impairment 
Dose adjustments in hepatic impairment are not necessary (see section 5.2). 
 
Paediatric population  
Use is not recommended in neonates, infants, children and adolescents. No clinical experience is yet 
available for patients younger than 18. 
 
Method of administration 
This medicinal product should be administered as a single intravenous bolus injection, manually, or by 
magnetic resonance injector (MR injector) over a period of time up to 30 seconds followed by a 25-
30 ml normal saline flush.  
 
4.3 Contraindications  
 
Hypersensitivity to the active substance or to any of the excipients. 
  
4.4 Special warnings and precautions for use  
 
Diagnostic procedures involving the use of MRI contrast agents should be carried out under the 
supervision of a physician with the prerequisite training and a thorough knowledge of the procedure to 
be performed. Appropriate facilities should be available for coping with any complication of the 
procedure, as well as for emergency treatment of potential severe reactions to the contrast agent itself.  
The usual safety precautions for magnetic resonance imaging must be observed, e.g., exclusion of 
cardiac pacemakers and ferromagnetic implants. 
As with other contrast enhanced diagnostic procedures, post-procedure observation of the patient is 
recommended, in particular in patients with a history of allergy, renal insufficiency, or adverse 
reaction. 
 
Hypersensitivity warning 
The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid, or cardiovascular 
reactions, or other idiosyncratic reactions should always be considered especially in those patients 
with a known clinical hypersensitivity, previous reaction of contrast media, a history of asthma, or 
other allergic disorders. Experience with other contrast media shows that the risk of hypersensitivity 
reactions is higher in those patients. Delayed reactions may occur (after hours to days).  
 
Caution should also be exercised in the following cases: 
 
Hypersensitivity reactions 
If hypersensitivity reactions occur (see section 4.8), administration of the contrast medium must be 
discontinued immediately and - if necessary - specific therapy instituted via a venous access. It is 
therefore advisable to use a flexible indwelling cannula for intravenous contrast medium 
administration. Due to the possibility of severe hypersensitivity reactions after intravenous contrast 
administration, preparedness for institution of emergency measures is necessary, e.g., appropriate 
medicinal products, an endotracheal tube, and a respirator should be at hand. 
 

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Renal impairment 
Since gadofosveset is cleared from the body primarily by urinary excretion, caution should be 
exercised in patients with impaired renal function (see section 4.2 and 5.2).  
 
Prior to administration of Ablavar, it is recommended that all patients are screened for renal 
dysfunction by obtaining laboratory tests. 
 
There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some 
gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment 
(GFR < 30 ml/min/1.73 m2). Patients undergoing liver transplantation are at particular risk since the 
incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with 
Ablavar, it should therefore be avoided in patients with severe renal impairment and in patients in the 
perioperative liver transplantation period unless the diagnostic information is essential and not 
available with non-contrast enhanced MRI. 
 
Haemodialysis shortly after Ablavar administration may be useful at removing Ablavar from the body. 
There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in 
patients not already undergoing haemodialysis. 
 
Elderly 
As the renal clearance of gadofosveset may be impaired in the elderly, it is particularly important to 
screen patients aged 65 years and older for renal dysfunction. 
 
Haemodialysis shortly after Ablavar administration in patients currently receiving haemodialysis may 
be useful at removing Ablavar from the body. In a clinical trial it was shown that gadofosveset can 
effectively be removed from the body by dialysis using high flux filters. 
 
There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in 
patients not already undergoing haemodialysis.  
 
Electrocardiographic changes 
Elevated levels of gadofosveset (e.g. repeated use in the short term [within 6-8 hours], or an 
inadvertent overdose > 0.05 mmol/kg) may be associated with mild QT prolongation (8.5 msec by 
Fridericia correction). In the situation of elevated levels of gadofosveset or underlying QT 
prolongation the patient should be carefully observed including cardiac monitoring. 
 
Vascular stents 
It has been shown in published studies that MRA in the presence of metallic stents causes artefacts. 
The reliability of lumen visualisation in a stented vessel with Ablavar has not been evaluated.   
 
Sodium 
This medicine contains 6.3 mmol sodium (or 145 mg) per dose. 
To be taken into consideration by patients on a controlled sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Because gadofosveset is bound to albumin, an interaction with other plasma protein bound active 
substances (e.g., ibuprofen and warfarin) is generally possible, i.e., a competition for the protein 
binding site can occur. However, in a series of in vitro drug interaction studies (in 4.5 % human serum 
albumin and human plasma), gadofosveset demonstrated no adverse interaction with digitoxin, 
propranolol, verapamil, warfarin, phenprocoumon, ibuprofen, diazepam, ketoprofen, naproxen, 
diclofenac and piroxicam at clinically relevant concentrations. In vitro studies using human liver 
microsomes did not indicate any potential to inhibit the cytochrome P 450 enzyme system. 
 
In a clinical study, it was shown that gadofosveset does not affect the unbound fraction of warfarin in 
plasma. The anticoagulant activity of warfarin was not altered and the efficacy of the medicinal 
product was not influenced. 

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Laboratory test interactions 
In clinical trials using Ablavar, no specific trends were observed that would signify a potential 
interaction of the medicinal product with laboratory test methods. 
 
4.6 Fertility, pregnancy and lactation  

 
Pregnancy 
There are no data from the use of Ablavar in pregnant women. Animal studies have shown 
reproductive toxicity at repeated high doses (see section 5.3). Ablavar should not be used during 
pregnancy unless the clinical condition of the woman requires use of the medicinal product. 
 
Breast-feeding 
Gadolinium containing contrast agents are excreted into breast milk in very small amounts (see section 
5.3). At clinical doses, no effects on the infant are anticipated due to the small amount excreted in milk 
and poor absorption from the gut. Continuing breastfeeding or discontinuing Ablavar for a period of 
24 hours after administration should be at the discretion of the physician and breast-feeding mother. 
 
 
 
4.7 Effects on ability to drive and use machines  
 
No studies on the effects on the ability to drive and use machine have been performed. Uncommonly, 
dizziness or vision problems may occur with this medicine. If a patient experiences these effects 
he/she should not drive or use machines 
 
4.8 Undesirable effects  
 
The most common adverse reactions were pruritus, paresthesia, headache, nausea, vasodilatation, 
burning sensation and dysgeusia. Most of the adverse reactions were mild to moderate in intensity.  
Most of the adverse reactions (80%) occurred within 2 hours. Delayed reactions (after hours to days) 
may occur. 
Clinical trial data  
Based on clinical trial experience in more than 1,800 patients, the following adverse reactions have 
been observed. 
 
The table below reports adverse reactions by MedDRA system organ classes (MedDRA SOCs). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.  
 
System Organ 
Class (MedDRA) 

Common 
( 1/100) 
 

Uncommon 
( 1/1,000 to  1/100)  

Rare 
( 1/10,000 to  1/1,000)  

Infections and 
infestations 

 Nasopharyngitis 
 

Cellulitis 
Urinary tract infection 
 

Immune system 
disorders 

 Hypersensitivity 
 

 

Metabolism and 
nutrition disorders 

 Hyperglycaemia 
Electrolyte imbalance (incl. 
Hypocalcemia) 
 

Hyperkalemia 
Hypokalemia  
Hypernatremia 
Appetite decreased 

Psychiatric 
disorders 

 Anxiety 
Confusion 
 

Hallucination 
Abnormal dreams 
 
 

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System Organ 
Class (MedDRA) 

Common 
( 1/100) 
 

Uncommon 
( 1/1,000 to  1/100)  

Rare 
( 1/10,000 to  1/1,000)  

 
 
 

Nervous system 
disorders 

Headache  
Paraesthesia  
Dysgeusia 
Burning sensation

Dizziness (excl. Vertigo) 
Tremor  
Hypoesthesia 
Parosmia  
Ageusia  
Muscle contractions 
involuntary 
 

 

Eye disorders   Vision abnormal 
Lacrimation increased  
 

Abnormal sensation in eye 
Asthenopia 
 

Ear and labyrinth 
disorders 

   Ear pain 
 

Cardiac disorders   Atrioventricular block first 
degree,  
Electrocardiogram QT 
prolonged,  
Tachycardia 
Electrocardiogram abnormal
 

Cardiac flutter 
Myocardial ischaemia 
Bradycardia  
Atrial fibrillation 
Palpitations   
Electrocardiogram ST 
segment depression,  
Electrocardiogram T wave 
amplitude decreased 
  

Vascular disorders Vasodilatation 
(incl. Flushing) 

Phlebitis  
Hypertension  
Peripheral coldness 
 

Anaphylactoid reaction  
Hypotension 
Arteriosclerosis 
 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Dyspnea  
Cough 
 

Respiratory depression 

Gastrointestinal 
disorders 

Nausea Vomiting 
Retching 
Diarrhea  
Abdominal pain 
Pharyngolaryngeal pain 
Abdominal discomfort 
Flatulence  
Hypoesthesia lips  
Salivary hypersecretion 
Dyspepsia  
Dry mouth  
Pruritus ani 
 

 

Skin and 
subcutaneous tissue 
disorders 

Pruritus Urticaria 
Rash 
Erythema  
Sweating increased  
 
 

Swelling face 
Clamminess 
 

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System Organ 
Class (MedDRA) 

Common 
( 1/100) 
 

Uncommon 
( 1/1,000 to  1/100)  

Rare 
( 1/10,000 to  1/1,000)  

 
 

Musculoskeletal 
and connective 
tissue disorders 

 Pain in limb 
Neck pain 
Muscle cramps  
Muscle spasms  
 

Muscle tightness 
Sensation of heaviness 

Renal and urinary 
disorders 

 Haematuria,  
Microalbuminuria,  
Glycosuria 
 

Micturition urgency 
Renal pain  
Urinary frequency 
 

Reproductive 
system and breast 
disorders 

 Genital pruritus,  
Genital burning sensation  

Pelvic pain 

General disorders 
and administration 
site conditions 

Feeling cold Pain,  
Chest pain  
Groin pain 
Fatigue  
Feeling abnormal 
Feeling hot  
Injection site pain, Injection 
site erythema, Injection site 
coldness  

Pyrexia 
Rigors 
Weakness 
Chest pressure sensation 
Injection site thrombosis 
Injection site bruising 
Injection site inflammation 
Injection site burning 
Injection site extravasation 
Injection site haemorrhage 
Injection site pruritus 
Sensation of pressure 
 

Injury, poisoning 
and procedural 
complications 

  Phantom limb pain 

 
Cases of nephrogenic systemic fibrosis (NSF) have been reported with other gadolinium-containing 
contrast agents (see section 4.4). 
 
As with other intravenous contrast agents, this medicinal product can be associated with 
anaphylactoid / hypersensitivity reactions characterised by cutaneous, respiratory and/or 
cardiovascular manifestations which may lead to shock. 
 
4.9 Overdose  
 
Ablavar can be removed by haemodialysis. However, there is no evidence that haemodialysis is 
suitable for prevention of nephrogenic systemic fibrosis (NSF). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties  
 
Pharmacotherapeutic group: Contrast media, paramagnetic contrast media, ATC code: V08CA. 
 
Ablavar is a formulation of a stable gadolinium diethylenetriaminepentaacetic acid (GdDTPA) chelate 
substituted with a diphenylcyclohexylphosphate group (gadofosveset trisodium), for use in magnetic 
resonance imaging (MRI). 

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Gadofosveset binds reversibly to human serum albumin. Protein binding enhances T1 relaxivity of 
gadofosveset up to 10 fold compared to non-protein bound gadolinium chelates. In human studies, 
gadofosveset substantially shortens blood T1 values for up to 4 hours after intravenous bolus injection. 
Relaxivity in plasma was measured to be 33.4 to 45.7 mM-1s-1 over the dose range of up to 
0.05 mmol/kg at 20 MHz. High resolution MRA scans of vascular structures are obtained up to one 
hour after administration of the medicinal product. The extended vascular imaging window for 
gadofosveset is attributed to enhanced relaxivity and extended residence in vascular space resulting 
from its plasma protein binding. No comparative studies with extracellular gadolinium contrast agents 
have been conducted. 
 
The safety and effectiveness of Ablavar in patients under 18 years of age have not been established.   
 
5.2 Pharmacokinetic properties  
 
Distribution 
The plasma concentration-time profile of intravenously administered gadofosveset conforms to a two-
compartment open model. After intravenous administration of 0.03 mmol/kg dose the mean half-life of 
the distribution phase (t1/2) was 0.48 ± 0.11 hours and the volume of distribution at steady state was 
148 ± 16 ml/kg, roughly equivalent to that of extracellular fluid. Plasma protein binding was in a range 
80% to 87% for up to the first 4 hours after injection.  
 
Biotransformation 
The results from various evaluations of plasma and urine samples indicated that gadofosveset does not 
undergo measurable metabolism. 
 
Elimination 
In healthy volunteers, gadofosveset was predominantly eliminated in the urine with 84% (range 79 – 
94%) of the injected dose (0.03 mmol/kg) excreted in the urine in 14 days. Ninety-four percent (94%) 
of the urinary excretion occurred in the first 72 hours. A small portion of gadofosveset dose was 
recovered in the faeces (4.7%, range 1.1 – 9.3%), indicating a minor role of biliary excretion in the 
disposition of gadofosveset. After intravenous administration of 0.03 mmol/kg dose renal clearance 
(5.51 ± 0.85 ml/h/kg) and total clearance (6.57 ± 0.97 ml/h/kg) were similar, and mean terminal 
elimination half-life was 18.5 ± 3.0 hours. 
 
Characteristics in patients 
 
Renal impairment 
In patients with moderate to severe renal impairment the half-life is markedly prolonged and the AUC 
increased by 2-3fold.  
 
Hemodialysis patients 
Gadofosveset can be removed from the body by hemodialysis. After bolus intravenous administration 
of 0.05 mmol/kg dose in patients requiring three times a week haemodialysis using high-flux filter, at 
the end of third dialysis session, the plasma concentration had declined to less than 15 % of the Cmax. 
During the dialysis sessions the mean half-life of plasma concentration decline was in the range 
5-6 hours. The mean dialysis clearance was between the range of 16-32 ml/h/kg. The high-flux 
dialysis filter was more efficient compared to the low-flux filter, therefore, use of a high-flux dialysis 
filter is recommended. 
 
Hepatic impairment 
Plasma pharmacokinetics and protein binding of gadofosveset were not significantly influenced by 
moderate hepatic impairment (Child Pugh B). A slight decrease in faecal elimination of gadofosveset 
was seen for the hepatic impaired subjects (2.7%) compared to normal subjects (4.8%). In one subject 
with moderate hepatic impairment and abnormally low serum albumin, total clearance and half-life of 
gadofosveset was indicative of faster clearance compared to subjects with moderate hepatic 
impairment and normal serum albumin levels. 
 

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5.3 Preclinical safety data  
 
Preclinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, acute toxicity, local tolerance, contact-sensitising potential, and genotoxicity. 
 
No carcinogenicity studies were performed. 
 
Repeated dose toxicity 
Repeated-dose toxicity studies revealed vacuolation of the tubular cells of the kidneys, with strong 
evidence for reversibility of the effect. No functional impairment was observed and electron 
microscopic investigations of the rat kidneys indicated that the observed vacuolation was primarily a 
storage phenomenon. Effects were of higher severity in rats than in monkeys, probably because of the 
higher renal clearance in rats. In monkeys, no renal effects were observed after single use even at a 
dose 100-times higher than the clinical dose. 
 
Reproduction toxicity 
In rabbits, an increased number of early resorptions and a slight but significant increase in the number 
of foetal anomalies (in particular hydrocephalus and malrotated limbs) were observed at doses at 
which no or slight maternal toxicity was observed (exposure was 2 and 5 times the expected human 
exposure, respectively). In an animal study, it was shown that less than 1% of the dose of gadofosveset 
administered enters breast milk. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
Fosveset 
Sodium hydroxide  
Hydrochloric acid 
Water for injections 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.  
 
6.3 Shelf life  
 
3 years. 
After first opening: the medicinal product should be used immediately. 
 
6.4 Special precautions for storage  
 
Keep the injection vial in the outer carton in order to protect from light. 
 
6.5 Nature and contents of container  
 
10 and 20 ml colourless type I glass vials with chloro- or bromobutyl elastomer stopper and 
aluminium bordered cap (plastic disk). 
Pack sizes: 
1, 5, or 10 vials  10 ml (in 10-ml glass vial) 
1, 5, or 10 vials  15 ml (in 20-ml glass vial) 
1, 5, or 10 vials  20 ml (in 20-ml glass vial) 
 
Not all pack sizes may be marketed. 
 

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6.6 Special precautions for disposal and other handling  
 
This medicinal product is supplied ready to use as a clear, colourless to pale yellow aqueous solution. 
Contrast media should not be used in case of severe discolouration, the occurrence of particulate 
matter, or defective container. 
Vials are not intended for the withdrawal of multiple doses. The rubber stopper should never be 
pierced more than once. After withdrawal of the solution from the vial, it should be used immediately.  
 
The peel-off tracking label included with the vials should be stuck onto patient record to enable 
accurate recording of the gadolinium contrast agent used. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER  
  
TMC Pharma Services Ltd., Finchampstead, Berkshire RG40 4LJ, UK 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/05/313/001 - 009 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION  
 
Date of first authorisation: 3 October 2005 
Date of latest renewal:  
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu 
 

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http://www.ema.europa.eu/


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURING AUTHORISATION HOLDER 
RESPONSIBLE FOR BATCH RELEASE  

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 

 
 
 

 
 

 
 

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A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer responsible for batch release 
 
Bayer Schering Pharma AG 
D – 13342 Berlin 
Germany 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
 CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to restricted medicinal prescription (See Annex 1: Summary of Product 
Characteristics, section 4.2) 
 
 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 
 OTHER CONDITIONS 
 
Risk Management Plan 
The MAH commits to performing the studies and additional pharmacovigilance activities 
detailed in the Pharmacovigilance Plan, as agreed in version 2.0 of the Risk Management Plan 
(RMP) presented in Module 1.8.2. of the Marketing Authorisation and any subsequent updates 
of the RMP agreed by the CHMP. 
 
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, any 
updated RMP should be submitted at the same time as the following Periodic Safety Update Report 
(PSUR). 
 
In addition, an updated RMP should be submitted: 
 When new information is received that may impact on the current Safety Specification, 

Pharmacovigilance Plan or risk minimisation activities 
 Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 

reached 
 At the request of the European Medicines Agency 
 
PSURs 
The MAH will continue to submit yearly PSURs unless otherwise specified by the CHMP. 
 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER PACKAGING - BOX 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ablavar 0.25 mmol/ml solution for injection 
 
Gadofosveset 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml Ablavar solution for injection contains 244 mg (0.25 mmol) gadofosveset trisodium equivalent to 
227 mg gadofosveset.. 
Each vial of 10 ml solution contains 2.44 g (2.50 mmol) of gadofosveset trisodium equivalent to 2.27g 
gadofosveset.  
Each vial of 15 ml solution contains 3.66 g (3.75 mmol) of gadofosveset trisodium equivalent to 3.41g 
gadofosveset . 
Each vial of 20 ml solution contains 4.88 g (5.00 mmol) of gadofosveset trisodium equivalent to 4.54g 
gadofosveset. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: fosveset, sodium hydroxide, hydrochloric acid, water for injections 
See the leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 vial 
5 vials 
10 vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use and diagnostic use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
The peel-off tracking label included with the vials should have the dose recorded on it and be stuck 
onto patient record  
 

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8. EXPIRY DATE  
 
EXP  
After first opening use immediately. 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the injection vial in the outer carton in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Discard any unused medium after each investigation. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
TMC Pharma Services Ltd., Finchampstead, Berkshire, RG40 4LJ, UK 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/313/001 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-10 ml-1 
vial 
EU/1/05/313/002 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-10ml-5 
vials  
EU/1/05/313/003 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-10ml-10 
vials 
EU/1/05/313/004 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-15ml-1 
vial 
EU/1/05/313/005 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-15ml-5 
vials 
EU/1/05/313/006 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-15ml-10 
vials 
EU/1/05/313/007 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-20ml-1 
vial 
EU/1/05/313/008 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-20ml-5 
vials 
EU/1/05/313/009 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-20ml-10 
vials 
 
 
13.  BATCH NUMBER 
 
Lot  
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 

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16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted.  

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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
Vial 15 and 20ml 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ablavar 0.25 mmol/ml solution for intravenous use 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml Ablavar solution contains 244 mg (0.25 mmol) gadofosveset trisodium equivalent to 227 mg of 
gadofosveset. 
 
Each vial of 15 ml solution contains 3.66 g (3.75 mmol) of gadofosveset trisodium equivalent to 3.41 
g of gadofosveset. 
Each vial of 20 ml solution contains 4.88 g (5.00 mmol) of gadofosveset trisodium equivalent to 4.54 
g of gadofosveset. 
 
 
3. LIST OF EXCIPIENTS 
 
Fosveset 
Sodium hydroxide  
Hydrochloric acid 
Water for injection 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
15 ml 
20 ml 
 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Ablavar should be administered as a single intravenous bolus injection, manually, or by magnetic 
resonance injector over a period of time up to 30 seconds followed by a 25-30 ml normal saline flush.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE  
 
EXP  

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After first opening use immediately 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the injection vial in the outer carton in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Discard any unused medium after each investigation. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
TMC Pharma Services Ltd., Finchampstead, Berkshire, RG40 4LJ, UK 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/313/004 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-15ml-1 
vial 
EU/1/05/313/005 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-15ml-5 
vials 
EU/1/05/313/006 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-15ml-10 
vials 
EU/1/05/313/007 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-20ml-1 
vial 
EU/1/05/313/008 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-20ml-5 
vials 
EU/1/05/313/009 Ablavar-0.25 mmol/ml-Solution for injection-Intravenous use-Vial (glass)-20ml-10 
vials 
 
13.  BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
 
 
 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
10 ML  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Ablavar 0.25 mmol/ml solution for injection 
Gadofosveset  
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use 
 
 
3. EXPIRY DATE 
 
EXP  
After first opening: the medicinal product should be used immediately. 
 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT,  BY VOLUME OR BY UNIT 
 
10 ml 
 
 
6. OTHER 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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B. PACKAGE LEAFLET 
 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Ablavar 0.25 mmol/ml solution for injection 
Gadofosveset  

 
Read all of this leaflet carefully before you are given this medicine. 
- Keep this leaflet. You may need to read it again. 
- If you have further questions, please ask the doctor giving you Ablavar (the radiologist) or the 

hospital/MRI-centre personnel 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or radiologist. 
 
 
In this leaflet:  
1. What Ablavar is and what it is used for 
2. Before you are given Ablavar 
3. How to use Ablavar 
4. Possible side effects 
5. How to store Ablavar 
6. Further information 
 
 
1. WHAT ABLAVAR IS AND WHAT IT IS USED FOR 
 
Ablavar is an injectable contrast medium for making a diagnostic image of the body's blood vessels in 
the abdomen or limb clearer. It is for use in adults only. 
 
Ablavar is for diagnostic use only. It is used to help detect changes in the blood vessels which are 
known or suspected to be abnormal. The diagnosis can be made with greater accuracy than without 
using this medicine.  
 
This medicine, a contrast agent with magnetic properties, helps to visualise the passage of blood 
through the vessels by brightening the blood for an extended period. This medicine is used together 
with an imaging technique called magnetic resonance imaging (MRI). 
 
If you have any questions or are not sure about something, ask the doctor or MRI-centre personnel. 
 
 
2. BEFORE YOU ARE GIVEN ABLAVAR 
 
Do not use Ablavar 
You must not be given Ablavar if you are allergic (hypersensitive) to gadofosveset or any of the 
other ingredients of this medicine (see section 6 of this leaflet). 
 
Take special care with Ablavar 
You will need special medical attention if allergy-like reactions occur. Tell your doctor 
immediately if you notice itching, a feeling of mild swelling in your throat or tongue, which might be 
a first sign of some allergy-like reaction. Your doctor will be mindful of other signs as well. 
 
Tell your doctor if: 
 you have a cardiac pacemaker or any ferromagnetic implant or a metallic stent in your 

body 
 you suffer from allergy (e.g. hay fever, hives) or asthma  
 you had any reactions to previous injections of contrast media 
 your kidneys do not work properly 
 you have recently had, or soon expect to have, a liver transplant 

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If any of these apply to you, your doctor will decide whether the intended examination is possible or 
not. 
 
Your doctor may decide to take a blood test to check how well your kidneys are working before 
making the decision to use this medicine, especially if you are 65 years of age or older. 
 
Children or adolescents under 18 years 
This medicine should not be used in children or adolescents under 18 year of age. 
 
Using other medicines 
Please tell your doctor if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. 
Your doctor will advise you what to do. 
 
Pregnancy and breast-feeding 
Ask your doctor for advice before taking any medicine. 
You must tell your doctor if you think you are or might become pregnant. 
It has not been proven that this medicine is safe to use during pregnancy. Your doctor or radiologist 
will consider this with you. This medicine must not be used in pregnant women unless strictly 
necessary.  
Tell your doctor if you are breast-feeding or about to start breast-feeding. Your doctor will discuss 
whether you should continue breast-feeding or interrupt breast-feeding for a period of 24 hours after 
you receive this medicine.  
 
Driving and using machines 
There are no studies on the effects on the ability to drive and use machines.  
This medicine can uncommonly cause dizziness or vision problems. If you get these effects you 
should not drive or use machines 
 
Important information about some of the ingredients of Ablavar 
This medicine contains 6.3 mmol sodium (or 145 mg) per dose. To be taken into consideration by 
patients on a controlled sodium diet. 
 
 
3. HOW TO USE ABLAVAR 
 
You will be asked to lie down on the MRI scanning bed. Scanning may start immediately after the 
Ablavar injection. After the injection you will be observed in case there might be any initial side 
effects. 
 
The usual dose 
 
The dose of this medicine varies depending on your weight. The doctor will decide how much 
medicine is needed for your examination. The dose is: 0.12 ml/kg body weight (equivalent to 
0.03 mmol/kg of body weight). 
Further information regarding the administration and handling of this medicine is given at the end of 
the leaflet. 
 
Method of administration 
This medicine is given as a rapid injection into a vein by a medical professional only. The usual 
injection site is the back of your hand or just in front of your elbow. 
 
 
Dose in special patient groups 
 

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The use of this medicine is not recommended in patients with severe kidney problems and patients 
who have recently had, or soon expect to have, a liver transplant. However if use is required you 
should only receive one dose of this medicine during a scan and you should not receive a second 
injection for at least 7 days.  
 
Elderly 
It is not necessary to adjust your dose if you are 65 years of age or older but you may have a blood test 
to check how well your kidneys are working.  
 
If you receive more Ablavar than you should have received: 
If you think you may have had an overdose talk to your doctor immediately. Your doctor will treat you 
should overdose occur. If necessary, this medicine can be removed from the body by haemodialysis 
using high-flux filters. 
 
If you have any further questions on the use of this medicine, please consult your doctor, the 
radiologist or MRI-centre personnel. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Ablavar can cause side effects, although not everybody gets them. 
 
If you have any of the following symptoms you should tell a doctor immediately: 
 

Ablavar can be associated with allergy-like reactions (anaphylactoid / hypersensitivity reactions) 
characterised by:- 

 skin reactions, (cutaneous reactions) 
 breathing difficulties and/or heart/ pulse-rate/ blood pressure disturbances which may lead 

to consciousness disorders  respiratory reactions, and /or cardiovascular manifestations 
which may lead to shock).  

 
Most of the side effects were mild to moderate in intensity. Most of the side effects (80%) occurred 
within 2 hours. Delayed effects (after hours to days) may occur. 
 
Below are listed the reported/experienced side effects by frequency): Very common: affects more 
than 1 user in 10 
Common:  affects 1 to 10 users in 100 
Uncommon:  affects 1 to 10 users in 1,000 
Rare:   affects 1 to 10 users in 10,000 
Very rare:  affects less than 1 user in 10,000 
Not known:  frequency cannot be estimated from the available data. 
 
The following is a list of side-effects observed in clinical trials: 
 
Common:  
Headache 
Tingling or numbness of the hands or feet 
Change of taste in mouth 
Burning sensation 
Warm feeling (vasodilatation) including flushing 
Nausea 
Itching 
Feeling cold. 
 
 
Uncommon:  

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Runny nose  
Sore throat 
Feeling anxious  
Confusion  
Allergy-like reaction 
Impairment of taste 
Dizziness 
Shaking 
Decreased feeling or sensitivity (especially of the skin) 
Sense of smell distortion 
Involuntary muscle contractions 
Abnormal vision 
Tear secretion increased 
Disturbed nerve signals in the heart (first degree) 
Fast heart beat 
Problems with the electrical rhythm of the heart (long QT) 
High blood pressure 
Swelling and clotting in a vein 
Coldness in the fingers and toes 
Shortness of breath 
Cough 
Vomiting 
Attempting to vomit 
Diarrhoea 
Stomach discomfort 
Stomach pain 
Pain in the throat 
Indigestion 
Dry mouth 
Wind 
Decreased feeling or sensitivity of the lips 
Increased production of saliva 
Anal itching 
Hives 
Reddening of the skin 
Rash 
Sweating increased 
Muscle cramps 
Muscle spasms 
Neck pain 
Pain in arms or legs 
Genital itching 
Genital burning sensation 
Pain 
Chest pain 
Tiredness 
Feeling abnormal 
Groin pain 
Feeling hot 
Injection site pain  
Injection site coldness 
Reddening of skin at the injection site 
Blood in the urine  
Proteins in the urine 
Sugar in the urine 
High sugar levels in the blood 

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Low calcium levels in the blood 
Unusual amount of salt in the body. 
 
Rare:  
Inflammation of the skin 
Urinary tract infection 
Abnormal dreams 
Seeing, feeling or hearing things that is not there 
Appetite decreased 
Eyesight disorders 
Abnormal eye sensation  
Ear pain 
Heartbeat irregularity/disturbed heart-chamber contractions (cardiac flutter, atrial fibrillation) 
problems with the electrical rhythm of the heart (ST segment/T wave abnormalities) 
Chest pain 
Slow heart beat 
Palpitations 
Thickening of the arteries due to cholesterol deposits 
Low blood pressure 
Shallow breathing 
Face swelling 
Sweatiness 
Muscle tightness 
Sensation of heaviness 
Urge to pass urine 
Kidney pain 
Passing urine frequently 
Lower abdominal pain 
Fever 
Shivering 
Weakness 
Chest pressure sensation 
Injection site blood clot 
Injection site bruising 
Injection site inflammation 
Injection site burning 
Fluid escaping from injection site into the surrounding tissue 
Injection site bleeding 
Injection site itching 
Sensation of pressure 
Phantom pain in the arms or legs 
Low or high potassium levels in the blood 
High sodium levels in the blood. 
 
There have been reports of nephrogenic systemic fibrosis (which causes hardening of the skin and may 
affect also soft tissue and internal organs) associated with use of other  gadolinium-containing contrast 
agents.  
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or radiologist. 
 
 
5. HOW TO STORE ABLAVAR 
 
Keep out of the reach and sight of children. 
 

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Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date 
refers to the last day of the month. 
 
Keep the injection vial in its outer carton in order to protect from light. 
 
After first opening, the medicine should be used immediately. 
 
Do not use this medicine if you notice severe discolouration, the occurrence of particulate matter or a 
defective container. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Ablavar contains 
 
- The active substance is gadofosveset.  1 ml contains 227 mg gadofosveset equivalent to 

244 mg/ml (0.25 mmol/millilitre) gadofosveset trisodium.  
 10 ml solution contains 2.27 g, 15 ml solution contains 3.41g and 20 ml solution contains 4.54 g 

of gadofosveset in a vial. 
 
- The other ingredients are fosveset, sodium hydroxide, hydrochloric acid, and water for injections.  
 
What Ablavar looks like and contents of the pack 
 
Ablavar is a clear, colourless to pale yellow liquid supplied in a rubber stoppered glass vial, with an 
aluminium seal, in individual cartons. The contents of the packs are:  
 
1, 5 or 10 injection vials with 10 ml solution for injection (in 10-ml glass vial) 
1, 5 or 10 injection vials with 15 ml solution for injection (in 20-ml glass vial) 
1, 5 or 10 injection vials with 20 ml solution for injection (in 20-ml glass vial) 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
  
TMC Pharma Services Ltd., Finchampstead, Berkshire RG40 4LJ , UK 
Tel:01252 842255 
 
  

 
This leaflet was last approved in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
<--------------------------------------------------------------------------------------------------------------------------
--- 
The following information is intended for medical or healthcare professionals only: 
 
Prior to administration of Ablavar it is recommended that all patients are screened for renal 
dysfunction by obtaining laboratory tests. 
 
There have been reports of nephrogenic systemic fibrosis (NSF) associated with use of some 
gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment 
(GFR< 30 ml/min /1.73 m2). Patients undergoing liver transplantation are at particular risk since the 

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http://www.ema.europa.eu/


28 

incidence of acute renal failure is high in this group. As there is a possibility that NSF may occur with 
Ablavar, it should therefore be avoided in patients with severe renal impairment and in patients in the 
perioperative liver transplantation period unless the diagnostic information is essential and not 
available with non-contrast enhanced MRI. If use of Ablavar cannot be avoided, the dose should not 
exceed 0.03 mmol/kg body weight. More than one dose should not be used during a scan. Because of 
the lack of information on repeated administration, Ablavar injections should not be repeated unless 
the interval between injections is at least 7 days.   
 
As the renal clearance of gadofosveset may be impaired in the elderly, it is particularly important to 
screen patients aged 65 years and older for renal dysfunction. 
 
Haemodialysis shortly after Ablavar administration may be useful at removing Ablavar from the body. 
There is no evidence to support the initiation of haemodialysis for prevention or treatment of NSF in 
patients not already undergoing haemodialysis. 
 
Ablavar should not be used during pregnancy unless the clinical condition of the woman requires use 
of gadofosveset. 
 
Continuing breast feeding or discontinuing Ablavar for a period of 24 hours after administration, 
should be at the discretion of the doctor and lactating mother. 
 
The peel-off tracking label included on the vials should be stuck onto the patient record to enable 
accurate recording of the gadolinium contrast agent used. The dose used should also be recorded. 
 
Ablavar is supplied ready to use as a clear, colourless to pale yellow aqueous solution. 
Contrast media should not be used in case of severe discolouration, the occurrence of particulate 
matter, or defective container. 
 
Vials containing Ablavar are not intended for the withdrawal of multiple doses. The rubber stopper 
should never be pierced more than once. After withdrawal of the solution from the vial, this medicinal 
product should be used immediately.  
 
Any remaining solution not used in one examination must be discarded. 
 
 

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