OPTISON 0.19 mg/ml dispersion for injection

OPTISON is an ultrasound contrast agent that helps to obtain clearer pictures (scan) of the heart during an echocardiography (a procedure where an image of the heart is obtained by using ultrasound). OPTISON improves the visualization of the inner cardiac walls in patients where the walls are difficult to see.

OPTISON contains microspheres (tiny gas bubbles) that after injection travel through the veins to the heart and fill the left heart chambers, allowing the doctor to visualise and asses the function of the heart.

This medicine is for diagnostic use only.

Do not use OPTISON

• if you are allergic (hypersensitive) to perflutren or to any of the ingredients of OPTISON.
• if you have severe pulmonary hypertension (systolic pulmonary artery pressure > 90 mm Hg).

Take special care with OPTISON

• if you have any known allergies.
• if you have a severe heart, lung, kidney or liver disease. The experience of OPTISON in severely ill patients is limited.
• if you have an artificial valve in your heart.
• if you have acute severe inflammation or sepsis.
• if you have a known blood clotting problem

Your heart activity and rhythm will be monitored when you get OPTISON.

Efficacy and safety in patients below 18 years has not been established.

When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses or other types of infections.

There are no reports of virus infections with albumin manufactured to European Pharmacopoeia specifications by established processes.

It is strongly recommended that every time you receive a dose of OPTISON the name and batch number of the product are recorded in order to maintain a record of the batches used.

Using other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without prescription.

Pregnancy and breast-feeding

The safety of OPTISON for use during human pregnancy has not been fully established. Therefore, the medicine should not be used in pregnancy unless benefit outweighs risk and it is considered necessary by the doctor. However, because OPTISON is based on human albumin (the main protein in our blood), it is highly unlikely that it will have any harmful effects in pregnancy.

It is not known whether OPTISON passes into human milk. Therefore, caution should be exercised when OPTISON is administered to nursing women.

Driving and using machines

No effects are known.

Important information about some of the ingredients of OPTISON

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ?sodium-free?.

OPTISON should only be administered by doctors experienced in the field of diagnostic ultrasound imaging.

OPTISON is administered via an intravenous injection to allow the microspheres to enter the heart chamber and fill the left heart chamber. OPTISON is injected during the ultrasound examination in order to allow the doctor to assess the function of your heart.

The recommended dose is 0.5 ml - 3.0 ml per patient. A dose of 3.0 ml is usually sufficient, but some patients may need higher doses. This dose might be repeated if needed. The duration of the useful imaging time is 2.5 - 4.5 minutes for a dose of 0.5 - 3.0 ml.

Immediately after injection of OPTISON, 10 ml of sodium chloride 9 mg/ml solution for injection or glucose 50 mg/ml solution for injection should be injected at a rate of 1 ml/s to optimise the effect of the contrast agent.

If you are given more OPTISON than you should
Effects suspected to be due to overdose have not been reported.

Like all medicines, OPTISON can cause side effects, although not everybody gets them.

Side effects to OPTISON are rare and usually not serious. In general the administration of human albumin has been associated with transient (non lasting)altered taste, nausea, flushing, rash, headache, vomiting, chills and fever. Rare severe allergic reactions (anaphylaxis) have been associated with the administration of human albumin products. Reported side effects following the use of OPTISON:

Common side effects (affects 1 to 10 users in 100):

- Dysgeusia (altered taste)
- Headache
- Flushing (redness)
- Warm sensation
- Feeling sick (nausea)

Uncommon side effects (affects 1 to 10 users in 1,000):

- Eosinophilia (increased number of a type of white blood cells in the blood) - Dyspnoea (difficulty in breathing)
- Chest pain

Rare side effects (affects 1 to 10 users in 10,000):

- Tinnitus (noises in the ear)
- Dizziness
- Paraesthesia (tingling sensations)
- Ventricular tachycardia (a series of rapid heartbeats)

Unknown frequency (side effects where frequency cannot be estimated from the available data): - Allergic type symptoms, for example, a severe allergic reaction or ? shock (anaphylaxis), swelling of the face (face oedema), an itchy skin eruption (urticaria).
- Visual disturbances

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Keep out of the reach and sight of children.

Do not use OPTISON after the expiry date which is stated on the label, after EXP.
The expiry date refers to the last day of that month.

Store upright in a refrigerator (2°C -8°C).
Storage at room temperature (up to 25°C) for 1 day is acceptable.
Do not freeze.

The contents of the OPTISON vial should be used within 30 minutes after the rubber stopper has been penetrated.

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.

What OPTISON contains

• The active substance is perflutren-containing microspheres of heat treated human albumin 5-8 x 10 8/ml, suspended in human albumin solution 1%. The approximate amount of perflutren gas in each ml of OPTISON is 0.19 mg
• The other ingredients are human albumin, sodium chloride, N-acetyltryptophan, caprylic acid, sodium hydroxide and water for injections.

What OPTISON looks like and contents of the pack

OPTISON is a dispersion for injection. It is a clear solution with white microsphere layer on top.

The product is supplied as 1 vial of 3 ml and 5 vials of 3 ml.

Not all pack sizes may be marketed

Marketing Authorisation Holder and Manufacturer

GE Healthcare AS
Nycoveien 1-2,
P.O.BOX 4220 Nydalen
NO-0401 Oslo, Norway

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien GE Healthcare BVBA Kouterveldstraat 20 BE-1831 Diegem TélTel 32 0 2 719 74 01 LuxembourgLuxemburg GE Healthcare BVBA Kouterveldstraat 20 BE-1831 Diegem BelgiëBelgiqueBelgien TélTel 32 0 2 719 74 01

Magyarország GE Healthcare SCE Handels GmbH Hungary Representative Office Akron u.2. H-2040 BUDAÖRS Tel. 36 23 410 410 GE Healthcare SCE Handels GmbH Representative Office Bulgaria World Trade Centre, Office 405-406 . 36 1040 Te. 35 92 973 3170

Malta Pharma-Cos Ltd Triq C. Portanier MT-Santa Venera HMR 11 Tel 356 21 441870 eská republika GE Healthcare SCE Handels GmbH Branch Office Czech Republic Vyskoilova 14221a CZ-140 28 Praha 4 Tel 420 224 446 179

Danmark GE Healthcare AS Park Allé 295 DK-2605 Brøndby Tlf 45 70 22 22 03 Nederland GE Healthcare BV Cygne Centre De Rondom 8 NL-5612 AP Eindhoven Tel 31 40 299 10 00 Deutschland GE Healthcare Buchler GmbH Co. KG Gieselweg 1 D-38110 Braunschweig Tel 49 5307 9300 Norge GE Healthcare AS Nycoveien 1-2 NO-0401 Oslo Tlf 47 23 18 50 50

Eesti GE Healthcare Estonia OÜ Mustamäe tee 46 EE 10621 Tallinn Tel 372 6260 061 Österreich GE Healthcare Handels GmbH Europlaza, Gebäude E Technologiestrasse 10 A-1120 Wien Tel 43 1 972 72-0

GE Healthcare A.E. 8-10 151 25 ATHENS 30 1 805 08 64 Polska GE Healthcare SCE Handels GmbH Poland Representative Office 2 Stawki Str. PL 00193 Warszawa Tel. 48 22 635 68866113

Portugal Satis Lda. Edificio Ramazzotti Av. do Forte, No 6-6A España GE Healthcare Bio-Sciences, S.A.U C Gobelas, 35-37 28023 La Florida Madrid Tel 34 91 663 25 00 P-2790-072 Carnaxide Tel 351 214 25 1300

France GE Healthcare SA 11, avenue Morane Saulnier F-78 140 Velizy Villacoublay Tél 33 1 34 49 54 54 Ireland GE Healthcare Limited Amersham Place Little Chalfont HP7 9NA - UK Tel 44 0 1 494 54 4000 România GE Healthcare SCE Handels GmbH Representative Office Romania Str. Navodari Nr. 42 Sc.2, et.2 RO-014108 BUCHAREST Tel 40 21 23 211 53 Slovenija HIGIEA d.o.o. Blatnica 10 SI-1236 Trzin Tel 386 1 589 7221

Ísland Isfarm ehf. Lyngháls 13 IS-110 Reykjavik Sími 354 540 8024 Slovenská republika GE Healthcare SCE Handels GmbH Branch Office Slovakia Floriánske nám. 2 SK-811 07 Bratislava Tel 421 2 5542 5948

Italia SuomiFinland

GE Healthcare Srl Via Galeno 36 I-20126 Milano Tel 39 02 26001 111 Oy GE Healthcare Bio-Sciences Ab Kuortaneenkatu 2 FIN-00510 Helsinki PuhTel 35 810 394 11

Phadisco Ltd 185 C-2235 357 22 715000 Sverige GE Healthcare AB Solna Strandväg 98 S-171 75 Stockholm Tel 46 08 559 504 00

Latvija Instrumentarium Medical SiA Meza Str. 4 LV-1048 Riga Tel 371 780 7086 United Kingdom GE Healthcare Limited Amersham Place Little Chalfont HP7 9NA UK Tel 44 0 1 494 54 4000

Lietuva
Nycomed East Europe
Marketing Service GmbH
?eimyni?kiu 3
LT ? 09312 Vilnius
Tel. +370 5210 9071

This leaflet was last approved in

-----------------------------------------------------------------------------------------------------------------------

The following information is intended for medical or healthcare professionals only:

The recommended dose is 0.5 ml - 3.0 ml per patient. A dose of 3.0 ml is usually sufficient, but some patients may need higher doses. The total dose should not exceed 8.7 ml per patient. The duration of the useful imaging time is 2.5 - 4.5 minutes for a dose of 0.5 - 3.0 ml. OPTISON could be repeatedly administered, however, the clinical experience is limited.

Use the smallest dose for adequate opacification of cavities since larger doses produce image blocking effects with the possibility of obscuring important information.

Like all parenteral products, the vials of OPTISON should be inspected visually for integrity of the container.

Vials are intended for single use only. Once the rubber stopper has been penetrated, the contents should be used within 30 minutes and any unused product discarded.

OPTISON in the non-resuspended form has a white layer of microspheres on top of the liquid phase that requires resuspension before use. Homogenous white suspension after resuspension. The following instructions should be followed:

• Cold solutions taken directly from the refrigerator should not be injected.
• Allow the vial to reach room temperature and inspect the liquid phase for particulate matter or precipitates before resuspension.
• Insert a 20 G plastic cannula in a large antecubital vein, preferably of the right arm. Attach a three-way stopcock to the cannula.
• The OPTISON vial must be inverted and gently rotated for approximately three minutes to completely resuspend the microspheres.
• Complete resuspension is indicated by a uniformly opaque white suspension and absence of any material on stopper and vial surfaces.
• OPTISON should be withdrawn with care into the syringe within 1 minute after resuspension.
• Any pressure instability within the vial should be avoided since it may cause disruption of microspheres and loss of contrast effect.Thus, vent the vial with a sterile spike or with a sterile 18 G needle before withdrawing the suspension into the injection syringe. Do not inject air into the vial as this will damage the product.
• Use the suspension within 30 minutes after withdrawal.
• OPTISON will segregate in an undisturbed syringe and must be resuspended before use.
• Resuspend the microspheres in the syringe immediately before injection by holding the syringe horizontally between the palms of the hands and rolling it quickly back and forth for no less than 10 seconds.
• Inject the suspension through the plastic cannula, no smaller than 20 G at a maximum injection rate of 1.0 ml/s. Warning: Never use any other type of route but the open flow connection. If injected otherwise OPTISON bubbles will be destroyed.
• Immediately before injection a careful visual inspection of the syringe is mandatory in order to ensure complete resuspension of the microspheres.

Immediately after injection of OPTISON, 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50 mg/ml (5%) solution for injection should be injected at a rate of 1 ml/s.

Alternatively the flushing may be performed by infusion. The infusion set should then be attached to the three-way stopcock and intravenous infusion started at a ?to keep open? (TKO) rate. Immediately after OPTISON injection the intravenous infusion should be wide open until contrast begins to fade from the left ventricle. The infusion should then be returned to a TKO rate.