SonoVue

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
SonoVue 8 microlitres/mL powder and solvent for dispersion for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each   mL of the dispersion contains 8 µL sulphur hexafluoride microbubbles, equivalent to 
45 micrograms. 
 
For the full list of excipients, see section 6.1 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for dispersion for injection. 
White powder  
Clear, colourless solvent   
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
This medicinal product is for diagnostic use only. 
 
SonoVue is for use with ultrasound imaging to enhance the echogenicity of the blood, or of fluids in 
the urinary tract which results in an improved signal to noise ratio. 
 
SonoVue should only be used in patients where study without contrast enhancement is inconclusive. 
 
Echocardiography 
SonoVue is a transpulmonary echocardiographic contrast agent for use in adult patients with suspected 
or established cardiovascular disease to provide opacification of cardiac chambers and enhance left 
ventricular endocardial border delineation. 
 
Doppler of macrovasculature 
SonoVue increases the accuracy in detection or exclusion of abnormalities in cerebral arteries and 
extracranial carotid or peripheral arteries in adult patients by improving the Doppler signal to noise 
ratio. 
SonoVue increases the quality of the Doppler flow image and the duration of clinically-useful signal 
enhancement in portal vein assessment in adult patients. 
 
Doppler of microvasculature 
SonoVue improves display of the vascularity of liver and breast lesions during Doppler sonography in 
adult patients leading to more specific lesion characterisation. 
 
Ultrasonography of excretory urinary tract 
SonoVue is indicated for use in ultrasonography of the excretory tract in paediatric patients from 
newborn to 18 years to detect vesicoureteral reflux. For the limitation in the interpretation of a 
negative urosonography, see section 4.4. and 5.1. 
 
4.2 Posology and method of administration 
 
This product should only be used by physicians experienced in diagnostic ultrasound imaging. 
Emergency equipment and personnel trained in its use must be readily available. 
 



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Posology 
 
Intravenous use  
The recommended doses of SonoVue in adults are: 
 B-mode imaging of cardiac chambers, at rest or with stress: 2 mL. 
 Vascular Doppler imaging: 2.4 mL. 
During a single examination, a second injection of the recommended dose can be made when deemed 
necessary by the physician.  
 
Elderly Patients 
The dose recommendations for intravenous administration also apply to elderly patients. 
 
Paediatric Patients 
The safety and efficacy of SonoVue in patients under 18 years of age has not been established for 
intravenous administration and use in echocardiography and vascular Doppler imaging.  
 
Intravesical use  
 In paediatric patients the recommended dose of SonoVue is 1 mL 
 
Method of administration  
For instructions on reconstitution of the medicinal product before administration see section 6.6. 
 
Intravenous use   
SonoVue should be administered immediately after drawing into the syringe by injection into a 
peripheral vein. Every injection should be followed by a flush with 5 mL of sodium chloride 9 mg/mL 
(0.9%) solution for injection. 
 
Intravesical use  
After introduction of a sterile 6F-8F urinary catheter into the bladder under sterile conditions, the 
bladder is emptied of urine and then filled with saline (normal sterile 0.9% sodium chloride solution) 
to approximately one third or half of its predicted total volume [(age in years + 2) x 30] mL. SonoVue 
is then administered through the urinary catheter. Administration of SonoVue is followed by 
completion of bladder filling with saline until patient has the urge to micturate or there is the first 
slight sign of back pressure to the infusion. Ultrasound imaging of the bladder and kidneys is 
performed during filling and voiding of the bladder. Immediately following the first voiding, the 
bladder may be refilled with saline for a second cycle of voiding and imaging, without the need of a 
second SonoVue administration.  A low mechanical index (≤ 0.4) is recommended for imaging the 
bladder, ureters, and kidney during ultrasonography of the urinary tract with contrast. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.  
 
Intravenous use of SonoVue is contraindicated in patients known to have right-to-left shunts, severe 
pulmonary hypertension (pulmonary artery pressure >90 mmHg), uncontrolled systemic hypertension, 
and in patients with adult respiratory distress syndrome. 
SonoVue must not be used in combination with dobutamine in patients with conditions suggesting 
cardiovascular instability where dobutamine is contraindicated. 
 
4.4 Special warnings and precautions for use 
 
Hypersensitivity reactions 
 
Use caution when treating anaphylaxis with epinephrine in patients on beta blockers since response 
may be poor or promote undesired alpha-adrenergic and vagotonic effects (hypertension, bradycardia). 
 



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Intravenous use 
 
Patients with unstable cardiopulmonary status 
ECG monitoring should be performed in high-risk patients as clinically indicated. It is recommended 
to keep the patient under close medical supervision during and for at least 30 minutes following the 
administration of SonoVue. 
 
Use extreme caution when considering the administration of Sonvue in patients with recent acute 
coronary syndrome or clinically unstable ischaemic cardiac disease, including: evolving or ongoing 
myocardial infarction, typical angina at rest within last 7 days, significant worsening of cardiac 
symptoms within last 7 days, recent coronary artery intervention or other factors suggesting clinical 
instability (for example, recent deterioration of ECG, laboratory or clinical findings), acute cardiac 
failure, Class III/IV cardiac failure, or severe rhythm disorders because in these patients allergy like 
and/or vasodilatory reactions may lead to life threatening conditions. SonoVue should only be 
administered to such patients after careful risk/benefit assessment and a closely monitoring of vital 
signs should be performed during and after administration. 
 
It should be emphasised that stress echocardiography not only can induce an ischaemic episode but 
also the stressors may induce predictable, dose-dependent effects on the cardiovascular system (e.g., 
increase in heart rate, blood pressure and ventricular ectopic activity for dobutamine,  or decrease in 
blood pressure for adenosine and dipyridamole) as well as unpredictable, hypersensitivity reactions. 
Therefore, if SonoVue is to be used in conjunction with stress echocardiography patients must have a 
stable condition verified by absence of chest pain or ECG modification during the two preceding days. 
Moreover, ECG and blood pressure monitoring should be performed during SonoVue-enhanced 
echocardiography with a pharmacological stress (e.g. with dobutamine).  
 
Other concomitant diseases 
Caution is advisable when administering the product to patients with: acute endocarditis, prosthetic 
valves, acute systemic inflammation and/or sepsis, hyperactive coagulation states and/or recent 
thromboembolism, and end-stage renal or hepatic disease, as the numbers of patients with those 
conditions who were exposed to SonoVue in the clinical trials were limited. 
 
Interpretation of voiding urosonography with SonoVue and limitations of use 
False negative cases can occur with voiding ultrasonography with SonoVue and have not been 
clarified (see section 5.1). 
 
Technical recommendation In animal studies, the application of echo-contrast agents revealed 
biological adverse reactions (e.g. endothelial cell injury, capillary rupture) by interaction with the 
ultrasound beam. Although these biological side effects have not been reported in humans, the use of a 
low mechanical index is recommended. 
 
Excipients 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
4.6 Pregnancy, lactation, and fertility 
 
Pregnancy 
 
No clinical data on exposed pregnancies are available. Animal studies do not indicate harmful effects 
with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see 
section 5.3 Preclinical safety data). As a precautionary measure, it is preferable to avoid the use of 



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SonoVue during pregnancy. 
 
Breastfeeding 
 
It is not known if sulphur hexafluoride is excreted in human milk. However, based on its rapid 
elimination from the body via the expired air, it is considered that the breastfeeding can be resumed 
two to three hours after administration of SonoVue. 
 
Fertility 
 
No clinical data are available. Animal studies do not indicate harmful effects on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
SonoVue has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Adult population-Intravenous use 
 
The safety of SonoVue after intravenous administration was evaluated in 4653 adult patients who 
participated in 58 clinical trials. The undesirable effects reported with SonoVue after intravenous 
administration were, in general, non-serious, transient and resolved spontaneously without residual 
effects. In clinical trials, the most commonly reported adverse reactions after intravenous 
administration are: headache, injection site reaction, and nausea. 
 
The adverse reactions are classified by System Organ Class and frequency, using the following 
convention: Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < /100), 
Rare (≥ 1/10,000 to < 1/1,000), Very rare (< 1/10,000), not known (cannot be estimated from the 
available data) 



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System Organ Class Adverse Drug Reactions 
Frequency Category 

Uncommon 
(≥ 1/1,000 to < 1/100) 

Rare 
(≥ 1/10,000 to < 1/1000)

Not known 
Cannot be estimated 
from available data 

Immune system 
disorders 

 Hypersensitivity*  

Nervous system 
disorders 

Headache, paraesthesia, 
dizziness, dysgeusia 

 Vasovagal reaction 
 

Eye disorders  Vision blurred,   
Cardiac disorders   Myocardial infarction** 

Myocardial ischemia** 
Kounis syndrome*** 

Vascular disorders Flushing Hypotension  
Gastrointestinal 
disorders 

Nausea, Abdominal pain  Vomiting 

Skin and subcutaneous 
tissue disorders 

Rash  
 

Pruritus  

Musculoskeletal, 
connective tissue and 
bone disorders 

 Back pain  

General disorders and 
administration site 
conditions 

Chest discomfort, 
injection site reaction, 
feeling hot 

Chest pain, pain, fatigue  

*   Cases suggestive of hypersensitivity may include: skin erythema, bradycardia, hypotension, dyspnoea, loss of 
consciousness, cardiac/cardio-respiratory arrest, anaphylactic reaction, anaphylactic shock. 

** In some of the cases of hypersensitivity, in patients with underlying coronary artery disease, myocardial 
ischemia and/or myocardial infarctions were also reported. 

***Allergic acute coronary syndrome 
 
In very rare cases, fatal outcomes have been reported in temporal association with the use of SonoVue. 
In all these patients there was a high underlying risk for major cardiac complications, which could 
have led to the fatal outcome. 
 
Paediatric population-Intravesical use 
 
The safety of SonoVue after intravesical administration was based on evaluation of published 
literature involving use of SonoVue in over 6000 paediatric patients (age range 2 days to 18 years). No 
adverse reactions were reported. 
 
Reporting of suspected adverse reactions  
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Since there have been no cases of overdose reported to date, neither signs nor symptoms of overdose 
have been identified. In a Phase I study doses up to 52 mL of SonoVue were administered to normal 
volunteers without serious adverse events being reported. In the event of overdose occurring, the 
patient should be observed and treated symptomatically. 
 
 



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5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Ultrasound contrast media  
ATC code: VO8DA05.  
Sulphur hexafluoride is an inert, innocuous gas, poorly soluble in aqueous solutions. There are 
literature reports of the use of the gas in the study of respiratory physiology and in pneumatic 
retinopexy. The addition of sodium chloride 9 mg/mL (0.9%) solution for injection to the lyophilised 
powder followed by vigorous shaking results in the production of the microbubbles of sulphur 
hexafluoride. The microbubbles have a mean diameter of about 2.5 µm, with 90% having a diameter 
less than 6 µm and 99% having a diameter less than 11 µm. Each millilitre of SonoVue contains 8 µL 
of the microbubbles.  The intensity of the reflected signal is dependent on concentration of the 
microbubbles and frequency of the ultrasound beam .The interface between the sulphur hexafluoride 
bubble and the aqueous medium acts as a reflector of the ultrasound beam thus enhancing blood 
echogenicity and increasing contrast between the blood and the surrounding tissues. 
  
Intravenous use 
At the proposed clinical doses for intravenous administration, SonoVue has been shown to provide 
marked increase in signal intensity of more than 2 minutes for B-mode imaging in echocardiography 
and of 3 to 8 minutes for Doppler imaging of the macrovasculature and microvasculature.  
 
Intravesical use 
For ultrasonography of the excretory urinary tract in paediatric patients, after intravesical 
administration, SonoVue increases the signal intensity of fluids within the urethra, bladder, ureters, 
and renal pelvis, and facilitates the detection of reflux of fluid from the bladder into the ureters. 
The efficacy of SonoVue for detection/exclusion of vesicoureteral reflux was studied in two published 
open label single centre studies. The presence or absence of vesicoureteral reflux with SonoVue 
ultrasound was compared to the radiographic reference standard. In one study including 183 patients 
(366 kidney-ureter units), SonoVue ultrasound was correctly positive in 89 out 103 units with reflux 
and correctly negative in 226 out of 263 units without reflux. In the second study including 228 
patients (463 kidney-ureter units), SonoVue ultrasound was correctly positive in 57 out of 71 units 
with reflux and correctly negative in 302 out of 392 units without reflux. 
 
5.2 Pharmacokinetic properties 
 
The total amount of sulphur hexafluoride administered in a clinical dose is extremely small, (in a 2 mL 
dose the microbubbles contain 16 µl of gas). The sulphur hexafluoride dissolves in the blood and is 
subsequently exhaled. 
 
After a single intravenous injection of 0.03 or 0.3 mL of SonoVue/kg (approximately 1 and 10 times 
the maximum clinical dose) to human volunteers, the sulphur hexafluoride was cleared rapidly. The 
mean terminal half-life was 12 minutes (range 2 to 33 minutes). More than 80% of the administered 
sulphur hexafluoride was recovered in exhaled air within 2 minutes after injection and almost 100% 
after 15 minutes.  
 
In patients with diffuse interstitial pulmonary fibrosis, the percent of dose recovered in expired air 
averaged 100% and the terminal half-life was similar to that measured in healthy volunteers. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, genotoxicity and toxicity to reproduction. Caecal lesions observed in some repeat-dose 
studies with rats, but not in monkeys, are not relevant for humans under normal conditions of 
administration.  

Intravesical local tolerance for SonoVue was also assessed. A single-dose study and a repeat-dose 
study, both followed by a treatment-free period, were performed in female rats with local toxicity 



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evaluated through macroscopic and histopathological examination of both kidneys, ureters, the urinary 
bladder and urethra. It did not reveal any test item-related lesions in any of the examined organs, in 
particular in the urinary bladder, in both the single-dose and the repeat-dose studies. It was therefore 
concluded that SonoVue is well tolerated in the urinary tract in the rat. 

 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder: 
Macrogol 4000 
Distearoylphosphatidylcholine 
Dipalmitoylphosphatidylglycerol Sodium 
Palmitic acid 
 
Solvent: 
Sodium chloride 9 mg/mL (0.9%) solution for injection. 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
2 years. 
 
Once reconstituted, chemical and physical stability has been demonstrated for 6 hours. From a 
microbiological point of view, the medicinal product should be used immediately. If not used 
immediately, in use storage times and conditions prior to use are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
The medicinal product does not require any special storage conditions. 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Type I colourless glass vial containing 25 mg of dry, lyophilised powder in an atmosphere of sulphur 
hexafluoride closed with a grey butyl rubber stopper and sealed with an aluminium crimp seal with a 
flip-off disc. A transfer system (MiniSpike). 
 
Type I clear glass pre-filled syringe containing 5 mL sodium chloride 9 mg/mL (0.9%) solution for 
injection. 
 
6.6 Special precautions for disposal  
 
Before use examine the product to ensure that the container and closure have not been damaged. 
 
SonoVue must be prepared before use by injecting through the septum 5 mL of sodium chloride 
9 mg/mL (0.9%) solution for injection to the contents of the vial. The vial is then shaken vigorously 
for twenty seconds after which the desired volume of the dispersion can be drawn into a syringe as 
follows: 
 



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1

v1.0-08/2000  ©BRG 2000

2 3
4 5

6 7 8

 
 
1. Connect the plunger rod by screwing it clockwise into the syringe. 
2. Open the MiniSpike transfer system blister and remove syringe tip cap. 
3. Open the transfer system cap and connect the syringe to the transfer system by screwing it in 

clockwise. 
4. Remove the protective disk from the vial. Slide the vial into the transparent sleeve of the 

transfer system and press firmly to lock the vial in place. 
5. Empty the contents of the syringe into the vial by pushing on the plunger rod. 
6. Shake vigorously for 20 seconds to mix all the contents in the vial to obtain a white milky 

homogeneous liquid. 
7. Invert the system and carefully withdraw SonoVue into the syringe. 
8. Unscrew the syringe from the transfer system. 
 
Do not use if the liquid obtained is clear and/or if solid parts of the lyophilisate are seen in the 
suspension. 
 
SonoVue should be administered immediately by injection into a peripheral vein for use in 
echocardiography and in vascular Doppler imaging in adults or by intravesical administration for use 
in ultrasonography of the excretory urinary tract in paediatric patients.  
 
If SonoVue is not used immediately after reconstitution the microbubble dispersion should be shaken 
again before being drawn up into a syringe. Chemical and physical stability of the microbubble 
dispersion has been demonstrated for 6 hours. 
 
The vial is for a single use only.  
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 



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7. MARKETING AUTHORISATION HOLDER 
 
Bracco International B.V.  
Strawinskylaan 3051 
NL - 1077 ZX Amsterdam 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/01/177/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 March 2001  
Date of latest renewal: 24 April 2006 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



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ANNEX II 
 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Bracco Imaging S.p.A.  
Via Ribes 5, Bioindustry Park 
Colleretto Giacosa - 10010 (TO)  
Italy 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic Safety Update Reports  
 
The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided for 
under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk Management Plan ( RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
 
 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 
 Obligation to conduct post-authorisation measures 

 
The MAH shall complete, within the stated timeframe, the below measures: 
 

Description Due date 

Post-authorisation efficacy study (PAES): in order to  assess subject management 
among children undergoing SonoVue-enhanced VUS in comparison with children 
undergoing VCUG for assessment of VUR, the MAH should conduct and submit 
the results of the observational cohort study (according to the agreed protocol). 

Final study 
report to be 
submitted by  

2Q 2021 



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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 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
SonoVue 8 microlitres/mL powder and solvent for dispersion for injection 
sulphur hexafluoride  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL of the dispersion contains 8 µLsulphur hexafluoride microbubbles, equivalent to 
45 micrograms.  
 
 
3. LIST OF EXCIPIENTS 
 
Macrogol 4000, distearoylphosphatidylcholine, dipalmitoylphosphatidylglycerol sodium, palmitic 
acid, Solvent: sodium chloride 9 mg/mL  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
1 powder vial, 1 pre-filled syringe of solvent, 1 transfer system 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous or intravesical use 
Read the package leaflet before use. 
For single use only  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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



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9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bracco International B.V., 
Strawinskylaan 3051, 
NL - 1077 ZX Amsterdam, 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/01/177/002 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
SonoVue 8 microlitres/mL powder for dispersion for injection 
sulphur hexafluoride 
 
 
2. METHOD OF ADMINISTRATION 
 
Intravenous or intravesical use  
 
 
3. EXPIRY DATE 
 
EXP:  
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
25 mg powder 
 
 
6. OTHER 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Sodium chloride 9 mg/mL solution for injection  
Solvent for SonoVue 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 mL 
 
 
6. OTHER 
 



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B. PACKAGE LEAFLET 



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Package leaflet: Information for the patient 
 

SonoVue 8 microlitres/mL powder and solvent for dispersion for injection 
sulphur hexafluoride 

 
Read all of this leaflet carefully before you are given this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What SonoVue is and what it is used for 
2. What you need to know before you are given SonoVue 
3. How SonoVue is given 
4. Possible side effects 
5. How to store SonoVue 
6. Contents of the pack and other information 
 
 
1. What SonoVue is and what it is used for 
 
SonoVue is for diagnostic use only. 
 
SonoVue is an ultrasound contrast agent that contains tiny bubbles filled with a gas called sulphur 
hexafluoride. 
 
If your are an adult  SonoVue helps to obtain clearer ultrasound pictures of your heart, your blood 
vessels and/or tissues of the liver and breast.   
 
SonoVue helps to obtain clearer pictures of the urinary tract in children. 
 
 
2. What you need to know before you are given SonoVue  
 
Do not use SonoVue: 
 
- If you are allergic to sulphur hexafluoride or any of the other ingredients of this medicine (listed 

in section 6). 
- If you have been told you have a right-to-left heart shunt. 
- If you have severe pulmonary hypertension (pulmonary artery pressure > 90mmHg). 
- If you have uncontrolled hypertension. 
- If you have adult respiratory distress syndrome (a severe, medical condition characterized by 

widespread inflammation in the lungs). 
- If you have been told not to take dobutamine (medicine that stimulates the heart) due to your 

severe heart disease. 
 
Warnings and precautions 
 
Please tell your doctor if in the past 2 days you have: 
- had frequent and/or repeated angina or chest pain, especially if you have history of heart 

disease,  
- had recent electrocardiography changes. 



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Talk to your doctor before you are given SonoVue if: 
- you had a recent myocardial infarction or a recent surgery on your coronary arteries, 
- you suffer from angina or chest pain or severe cardiac disease, 
- you suffer from severe heart rhythm disorders, 
- your cardiac disease has worsened recently, 
- you have an acute inflammation of the cardiac envelope (endocarditis), 
- you have artificial heart valves, 
- you have an acute general inflammation or infection, 
- you have known blood clotting problem,  
- you have severe kidney or liver diseases, 
 
If you are given SonoVue together with a medicine, exercise or a device that stimulates the heart in 
order to visualise your heart under stress work, your heart activity, your blood pressure and rhythm 
will be monitored. 
 
Children and adolescents  
For patients under 18 years of age SonoVue can be used only for ultrasound of the urinary tract. 
 
Other medicines and SonoVue 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
In particular, please tell your doctor if you are taking beta-blockers (medicines for heart disease and 
hypertension or for glaucoma in eye drops). 
 
Pregnancy and breastfeeding 
 
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before you are given this medicine. 
 
It is not known if SonoVue passes into breast milk. However you must stop breastfeeding for two to 
three hours after your ultrasound examination. 
 
Driving and using machines 
 
SonoVue does not affect the ability to drive and use machines.  
 
SonoVue contains sodium 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-
free’. 
 
 
3. How SonoVue is given 
 
SonoVue is given to you by medical or healthcare professionals who are experienced in this type of 
examination.  
 
For ultrasound scan of heart or your blood vessels and/or tissues of the liver and breast in adults:the 
dose to be administered into a vein  will be calculated for you depending on which part of your body is 
being examined. The recommended dose is 2 or 2.4 mL per patient. This dose might be repeated if 
needed up to 4.8 mL. 
 
For ultrasound scan of urinary tract in children the recommended dose is 1 mL per patient to be 
administered into the bladder as follows:  
After emptying the bladder, a saline solution will be introduced into the bladder via a thin tube. 
SonoVue will then be administered through the thin tube and will be followed by administration of 



 22

saline to continue filling the bladder. The filling and emptying of the bladder with saline solution may 
be repeated if needed.  
 
If you have a serious pulmonary or cardiac condition you will be under close medical supervision 
during and for at least 30 minutes after the injection of SonoVue. 
 
If you are given more SonoVue than you should  
 
Overdose is not likely to happen since SonoVue is given by a doctor. In the case of overdose the 
doctor will take appropriate action. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
Most of the side effects to SonoVue are rare and usually not serious. However, some patients may 
experience serious side effects and may require treatment. 
 
Tell your doctor straight away if you notice any of the following side effects, you may need medical 
treatment: swelling of the face, lips, mouth or throat which may make it difficult to swallow or 
breathe; skin rash; hives; swelling of the hands, feet or ankles. 
 
The following side effects have been reported with SonoVue: 
 
Uncommon side effects (may affect up to 1 in 100 people):  
- Headache 
- Numbness 
- Dizziness 
- Strange taste in the mouth  
- Redness 
- Chest discomfort 
- Feeling sick (nausea) 
- Abdominal pain 
- skin rash 
- Feeling hot 
- Local reactions where the injection was given such as: pain or an unusual sensation at the 

injection site 
 
Rare (may affect up 1 in 1,000 people): 
- Blurred vision 
- Decrease in blood pressure 
- Itching 
- Back pain 
- Pain in general  
- Chest pain  
- Fatigue 
- Severe and less severe allergic reaction (including redness of the skin, decrease in heart rate, 

decrease in blood pressure, breathlessness, loss of consciousness, cardiac/cardio-respiratory 
arrest or more severe reaction with difficulties in breathing and dizziness) 

 
Not known (frequency cannot be estimated from the available data): 
- Chest pain, radiating to the neck or the left arm, which can be a sign of a potentially serious 

allergic reaction called Kounis syndrome 
- Faintness 
- In some of the cases of allergic reactions, in patients with cardiac blood vessel disease, lack of 

oxygen supply of the heart or cardiac arrest were reported  
- Vomiting 



 23

 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store SonoVue 
 
Keep this medicine out of the sight and reach of children 
Do not use this medicine after the expiry date which is stated on the label. The expiry date refers to the 
last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 
SonoVue dispersion should be administered to you within six hours of its preparation. 
 
 
6. Contents of the pack and other information 
 
What SonoVue contains 
 
- The active substance is sulphur hexafluoride in the form of microbubbles. 
- The other ingredients are: macrogol 4000, distearoylphosphatidylcholine, 

dipalmitoylphosphatidylglycerol sodium, palmitic acid. 
The glass syringe contains sodium chloride 9 mg/mL (0.9%) solution for injection. 
 
What SonoVue looks like and contents of the pack 
 
SonoVue is a kit which includes a glass vial containing white powder, a glass syringe containing the 
solvent and a transfer system. 
 
Marketing Authorisation Holder and Manufacturer: 
 
Marketing authorisation holder 
Bracco International B.V.  
Strawinskylaan 3051 
NL - 1077 ZX Amsterdam 
The Netherlands 
 
Manufacturer: 
Bracco Imaging S.p.A.  
Via Ribes 5, Bioindustry Park 
Colleretto Giacosa - 10010 (TO)  
Italy 
 
This leaflet was last revised on  
 
Other sources of information 
 
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 healthcare professionals only: 



 24

 
If SonoVue is not used immediately after reconstitution the dispersion will be shaken again before 
being drawn up into a syringe. 
The product is for a single examination only. Any unused liquid remaining at the end of an 
examination must be discarded. 
 
Reconstitution instructions: 
 

1

v1.0-08/2000  ©BRG 2000

2 3
4 5

6 7 8

 
 
1. Connect the plunger rod by screwing it clockwise into the syringe. 
2. Open the MiniSpike transfer system blister and remove syringe tip cap. 
3. Open the transfer system cap and connect the syringe to the transfer system by screwing it in 

clockwise. 
4. Remove the protective disk from the vial. Slide the vial into the transparent sleeve of the 

transfer system and press firmly to lock the vial in place. 
5. Empty the contents of the syringe into the vial by pushing on the plunger rod. 
6. Shake vigorously for 20 seconds to mix all the contents in the vial to obtain a white milky 

homogeneous liquid. 
7. Invert the system and carefully withdraw SonoVue into the syringe. 
8. Unscrew the syringe from the system. 
 
After reconstitution, SonoVue is a homogeneous white milky dispersion.  
 
Do not use if the liquid obtained is clear and/or if solid parts of the lyophilisate are seen in the 
suspension. 
 
SonoVue dispersion should be administered within six hours of its preparation. 
Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 



 25

you no longer use. These measures will help protect the environment. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET