Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: GE Healthcare AS, Nycoveien 1, NO-0485, Oslo, Norway
Pharmacotherapeutic group: Ultrasound contrast medium
ATC Code: V08DA01
When used in conjunction with diagnostic ultrasound, OPTISON provides opacification of cardiac chambers, improvement in delineation of endocardial borders, enhancement of the Doppler signal, and visualisation of wall motion and blood flow within the heart.
The ultrasound echoes from blood and biological soft tissues such as fat and muscles are generated at interfaces due to small differences in the ultrasonic properties of the tissues. The ultrasonic properties of microspheres containing perflutren are very different from that of soft tissue and will generate strong echoes.
OPTISON consists of perflutren -containing microspheres. The microspheres have a mean diameter of 2.5-4.5 microns and concentrations of 5-8 × 108 microspheres/ml. Microspheres in this size range contribute to the contrast effect by generating strongly enhanced echoes.
As OPTISON consists of microspheres that are stable and small enough for transpulmonary passage, it will also give enhanced echo signals in the left heart cavities.
As a consequence of the complex relationship between the concentration of the microspheres and the ultrasound signal, data processing within the ultrasound equipment and the fact that each individual responds differently due to variability in cardiac and pulmonary function, a strict dose/response relationship cannot be defined. The dose of OPTISON will therefore have to be adjusted individually, although clinical studies have shown that an initial dose of 0.5-3.0 ml per patient can be recommended for left heart opacification. Higher doses produce greater contrast effect of longer duration. Duration of useful contrast effect at the recommended dose is adequate to perform a complete echocardiographic examination including Doppler assessment.
Use the smallest dose for adequate opacification of cavities since larger doses produce image blocking effects with the possibility of obscuring important information.
In two uncontrolled studies including a total of 42 children and adolescents, aged 8 months to 19 years, the safety profile appeared to be similar to that seen in adults. Doses administered in one study were 0.2 ml above 25 kg body weight and 0.1ml under 25 kg, and in a second study 0.5ml above 20 kg body weight and 0.3 ml under 20 kg, by bolus peripheral intravenous injection followed by a saline flush. Low mechanical index was used for ultrasound imaging.
The effect of OPTISON on pulmonary haemodynamics was studied in a prospective, open-label study of 30 patients scheduled for pulmonary artery catheterisation, including 19 with an elevated baseline pulmonary arterial systolic pressure (PASP) (>35 mmHg; mean 70.1±33.0 mmHg; range 36.0-176.0 mmHg) and 11 with a normal PASP (≤35 mmHg; mean 29.3±4.6 mmHg; range 22.0-35.0 mmHg). Systemic haemodynamic parameters and ECGs were also evaluated. No clinically important pulmonary haemodynamic, systemic haemodynamic, or ECG changes were observed. This study did not assess the effect of OPTISON on visualisation of cardiac or pulmonary structures.
Following intravenous injection of 0.21 to 0.33 ml/kg of OPTISON to healthy volunteers, the perflutren component of OPTISON was rapidly and nearly completely eliminated in less than 10 minutes with a dominating pulmonary elimination half-life of 1.3±0.7 minutes. The perflutren levels detected in blood following this dosage were too low and transient to accurately determine pharmacokinetic parameters.
The disposition and elimination of the albumin microspheres have not been studied in humans. Information obtained from a preclinical study in rats with 125I-labelled albumin microspheres indicated that microspheres were rapidly cleared from the circulation, and radio-labelled microspheres, albumin shells and 125I were taken up primarily in the liver. The primary route of elimination of radioactivity was the urine. High levels of radioactivity were also retained in lungs for a considerable time, approx. 10% of the total dose 40 minutes after dose administration (cf. 35% in liver).
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, acute and repeated dose toxicity and genotoxicity. In the rabbit embryotoxicity study, a significant increase in the number of foetuses with dilated ventricles in the brain was observed (see section 4.6). No such finding was observed in the rat embryotoxicity study.
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