Consumer medicine information

1. Why am I using DEFINITY^®?

DEFINITY^® contains the active ingredient perflutren. DEFINITY^® is used in patients on contrast-enhanced diagnostic ultrasound imaging to improve characterisation of focal lesions of the liver and kidney. It is also used in patients with suboptimal echocardiograms to provide opacification of cardiac chambers, improvement of left ventricular endocardial border delineation and assessment of regional wall motion at both rest and stress.
For more information, see Section 1. Why am I using DEFINITY^®? in the full CMI.

2. What should I know before I use DEFINITY^®?

Do not use if you have ever had an allergic reaction to DEFINITY^®, Polyethylene glycol or any of the ingredients listed at the end of the CMI.
Talk to your doctor if you have any other medical conditions especially if you are diagnosed with Sickle Cell Disease, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use DEFINITY^®? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DEFINITY^® and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use DEFINITY^®?

• Your doctor will decide how much you will be given DEFINITY^®. This depends on which organ (liver, kidney or heart) is being examined and other factors such as weight.

• DEFINITY^® is given as an injection or infusion (drip) into a vein.

5. What should I know while using DEFINITY^®?

6. Are there any side effects?

Common side effects are headache, flushing, dizziness, altered taste, back pain, pain at the injection site.
Serious side effects could be swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing; changes in your heart rate; feeling faint; nausea, vomiting; rash, itchin, hives; allergic reaction/anaphylactic (shortness of breath or difficulty breathing, slow heart rate, dizziness or light-headedness, feeling unusually tired or weak); moderate to severe back pain and vaso occlusive crisis for patients with Sickle Cell Disease. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Perflutren.

2 Qualitative and Quantitative Composition

The perflutren lipid microspheres are composed of perflutren encapsulated in an outer lipid shell consisting of (R)-hexadecanoic acid, 1-[(phosphonoxy)methyl]-1,2-ethanediyl ester, monosodium salt (abbreviated DPPA); (R)-4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(l-oxohexadecyl)oxy]-3,4,9-trioxa-4-phosphapentacosan-l-aminium, 4-oxide, inner salt (abbreviated DPPC); and (R) á-[6-hydroxy-6-oxido-9-[(1-oxohexadecyl)oxy] 5,7,11-trioxa-2-aza-6-phosphahexacos-1-yl]- ω-methoxypoly(ox-1,2-ethanediyl), commonly called N-(methoxypolyethylene glycol 5000 carbamoyl)-1,2-dipalmitoyl-sn-glycero-3- phosphatidylethanolamine, monosodium salt (abbreviated MPEG5000 DPPE).
Prior to Vialmix activation, the Definity vial contains 6.52 mg/mL perflutren in the headspace. Each mL of the clear liquid contains 0.75 mg lipid blend (consisting of 0.045 mg DPPA, 0.401 mg DPPC, and 0.304 mg MPEG5000 DPPE), 103.5 mg propylene glycol, 126.2 mg glycerin, 2.34 mg monobasic sodium phosphate monohydrate, 2.16 mg dibasic sodium phosphate heptahydrate, and 4.87 mg sodium chloride in Water for Injection. The pH is 6.2-6.8.
After activating the contents of the vial in a Vialmix, each mL of the milky white suspension contains a maximum of 1.2 x 10¹⁰ perflutren lipid microspheres, and about 1.1 mg/mL perflutren. The microsphere particle size parameters are listed in Table 1:
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DEFINI01.gif Octafluoropropane and perfluoropropane are synonyms for perflutren.

3 Pharmaceutical Form

Definity contains a clear, colourless, sterile, nonpyrogenic, hypertonic liquid, which upon activation with the aid of a Vialmix, provides a homogeneous, opaque, milky white injectable suspension of perflutren lipid microspheres.

4 Clinical Particulars

4.9 Overdose

The clinical consequences of overdosing with activated Definity are not known. Single doses of up to 100 microL/kg and multiple doses up to 150 microL/kg were tolerated well in phase I clinical trials.
Treatment of an overdose should be directed toward the support of all vital functions and prompt institution of symptomatic therapy (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. No evidence of genotoxicity was found in the following studies with activated Definity:
1) bacterial mutagenesis assay (Ames assay); 2) in vitro mammalian mutagenesis assay; 3) in vitro human lymphocyte chromosome aberration assay; and 4) in vivo rat micronucleus assay.
Carcinogenicity. Studies with activated Definity have not been performed to evaluate carcinogenic potential.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Chemical structure. Perflutren is chemically characterized as 1,1,1,2,2,3,3,3-octafluoropropane. It has a molecular weight of 188, empirical formula of C₃F₈ and has the following structural formula:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSPERFLU.gif CAS number. The CAS number of perflutren is [76-19-7].
The physical and chemical characteristics of perflutren gas are provided in Table 6.
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DEFINI06.gif

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DEFINIST.gif