- 1. NAME OF THE MEDICINAL PRODUCT
- 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
- 3. PHARMACEUTICAL FORM
- 4. CLINICAL PARTICULARS
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. PHARMACOLOGICAL PROPERTIES
- 6. PHARMACEUTICAL PARTICULARS
- 7. MARKETING AUTHORISATION HOLDER
- 8. MARKETING AUTHORISATION NUMBER(S)
- 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
- 10. DATE OF REVISION OF THE TEXT
1.NAME OF THE MEDICINAL PRODUCT
Luminity 150 microlitres/ml gas and solvent for dispersion for injection/infusion
2.QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains a maximum of 6.4 x 109
Excipient(s) with known effect
Each ml contains 2.679 mg sodium
For the full list of excipients, see section 6.1.
Gas and solvent for dispersion for injection/infusion
Colourless, uniformly clear to translucent liquid.
This medicinal product is for diagnostic use only.
Luminity is an ultrasound
4.2Posology and method of administration
Luminity should only be administered by trained physicians with technical expertise in performing and interpreting contrast echocardiograms, and appropriate resuscitation equipment should be available in case of cardiopulmonary or hypersensitivity reactions (see section 4.4).
Bolus intravenous injection using
The recommended dose is multiple injections of 0.1 to 0.4 ml of dispersion, followed by a 3 to 5 ml bolus of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) solution for injection to maintain optimal contrast enhancement. The total dose of perflutren should not exceed 1.6 ml.
Bolus intravenous injection using fundamental imaging technique at rest:
The recommended dose is 10 microlitre dispersion/kg by slow bolus intravenous injection, followed by a 10 ml bolus of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) solution for injection. If necessary, a second 10 microlitre dispersion/kg dose followed by a second 10 ml bolus of sodium
chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) solution for injection may be administered 5 minutes after the first injection to prolong contrast enhancement.
Intravenous infusion using
The recommended dose via an intravenous infusion is 1.3 ml dispersion added to 50 ml of sodium chloride 9 mg/ml (0.9%) or glucose 50 mg/ml (5%) solution for injection. The rate of infusion should be initiated at 4 ml/minute, but titrated as necessary to achieve optimal image enhancement, not to exceed 10 ml/minute.
The safety and efficacy of Luminity in children and adolescents below 18 years have not been established. No data are available.
Patients with hepatic impairment
Luminity has not been specifically studied in patients with hepatic impairment. Use in this patient group should be on the basis of a benefit risk assessment by the physician.
Patients with renal impairment
Luminity has not been specifically studied in patients with renal impairment. Use in this patient group should be on the basis of a benefit risk assessment by the physician.
Luminity has not been specifically studied in elderly patients. Use in this patient group should be on the basis of a benefit risk assessment by the physician.
Method of administration
Before administering Luminity, the medicinal product must be activated by using a mechanical shaking device, the Vialmix, see section 6.6.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
4.4Special warnings and precautions for use
This product must only be administered intravenously.
Luminity should not be used with fundamental imaging technique for stress echocardiography since efficacy and safety have not been established.
Patients with unstable cardiopulmonary status
Patients with unstable cardiopulmonary status should be monitored during and for at least 30 minutes following Luminity administration. For such patients monitoring should include vital sign measurements, electrocardiography, and, if clinically appropriate, cutaneous oxygen saturation. Resuscitation equipment and trained personnel must always be readily available.
Patients with adult respiratory distress syndrome, endocarditis, prosthetic heart valves, systemic inflammation, sepsis, hyperactive coagulation and/or recurrent thromboembolism
Luminity should be used only after careful consideration and such use should be monitored closely during administration in patients with adult respiratory distress syndrome, endocarditis, a heart with prosthetic valves, acute states of systemic inflammation or sepsis, known states of hyperactive coagulation and/or recurrent thromboembolism.
Serious immediate hypersensitivity reactions (eg: anaphylaxis, anaphylactic shock and anaphylactoid reactions, hypotension and angioedema) have been reported following the administration of Luminity. Patients should be closely monitored and administration should be under the direction of a physician experienced in the management of hypersensitivity reactions including severe allergic reactions, which might require resuscitation. Emergency equipment and personnel trained in its use must be readily available.
Caution should be exercised in patients with clinically significant pulmonary disease, including diffuse interstitial pulmonary fibrosis and severe chronic obstructive pulmonary disease, as no studies have been performed in these patients.
- Optison - perflutren
Prescription drugs listed. Substance: "Perflutren"
Patients with Cardiac Shunts
The safety of Luminity in patients with
Patients on mechanical ventilation
The safety of microspheres in patients on mechanical ventilation has not been established. Caution should be exercised when considering the administration of Luminity to these patients.
Administration and mechanical activation procedure
Luminity should not be administered by methods not specified in section 4.2 (e.g.
If Luminity is administered directly to the patient without undergoing the mechanical activation procedure using the Vialmix (see section 6.6), the product will not produce its intended effect.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium- free’
4.5Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed and no other forms of interaction have been identified.
4.6Fertility, pregnancy and lactation
For perflutren, no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition
or postnatal development (see section 5.3). Caution should be exercised when prescribing to pregnant women.
It is not known whether Luminity is excreted in human breast milk. Therefore, caution should be exercised when Luminity is administered to
Animal studies do not indicate direct or indirect harmful effects on fertility.
4.7Effects on ability to drive and use machines
As Luminity has no pharmacologic effect, and on the basis of its pharmacokinetic and pharmacodynamic profiles, no or negligible influence is expected with the use of this product on the ability to drive or use machines.
Summary of the safety profile
The reported adverse reactions following the use of Luminity in pivotal and supportive trials (total of 2,526 patients) occur within minutes after administration and usually resolve without therapeutic intervention within 15 minutes. The most frequently reported adverse reactions are: headache (2.0%), flushing (1.0%) and back pain (0.9%).
Tabulated list of adverse reactions
Adverse reactions were reported with the following frequencies (Very common ≥ 1/10; Common
≥1/100 to < 1/10; Uncommon ≥ 1/1,000 to < 1/100; Rare ≥ 1/10,000 to < 1/1,000; Very rare
<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Immune system disorders
Not known: Allergic type reactions, anaphylaxis, anaphylactic
shock and anaphylactoid type reactions, hypotension, angioedema,
lip swelling, bronchospasm, rhinitis, upper airway swelling, throat
tightness, facial swelling, eye swelling
Nervous system disorders
Uncommon: Dizziness, dysgeusia
Not known: seizures, facial hypoaesthesia, loss of consciousness
Not known: Abnormal vision
Rare: Bradycardia, Tachycardia, Palpitations
Not known: Cardiac arrest, ventricular arrhythmias (ventricular
fibrillation, ventricular tachycardia, premature ventricular
contactions), asystole, atrial fibrillation, cardiac ischaemia,
supraventricular tachycardia, supraventricular arrhythmia
Rare: Syncope, hypertension, peripheral coldness
Respiratory, thoracic and
Uncommon: Dyspnoea, Throat Irritation
Rare: Respiratory Distress, Cough, Dry Throat
Not known: Respiratory arrest, decreased oxygenation, hypoxia,
Uncommon: Abdominal Pain, diarrhoea, nausea, vomiting,
Not known: Tongue disorder
Skin and subcutaneous
Uncommon: Pruritus, increased sweating
Rare: Rash, urticaria, erythema, erythematous rash
Uncommon: Back pain
connective tissue disorders
Rare: Arthralgia, flank pain, neck pain, muscle cramp
Not known: Muscle spasm, musculoskeletal pain,
musculoskeletal discomfort, myalgia, hypertonia
General disorders and
Uncommon: Chest Pain, fatigue, feeling hot, injection site pain
Rare: Pyrexia, rigors
Rare: Abnormal electrocardiogram
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.
The clinical consequences of overdose with Luminity are not known. Single doses of up to
100 microlitres dispersion/kg and multiple doses up to 150 microlitres dispersion/kg were tolerated well in Phase I clinical trials. Treatment of an overdose should be directed towards the support of all vital functions and prompt institution of symptomatic therapy.
Pharmacotherapeutic group: ultrasound contrast media, microspheres of phospholipids, ATC Code: V08DA04
The product consists of lipid encapsulated perflutren microspheres. Microspheres in the 1 to < 10 µm diameter size range contribute to the contrast effect by generating strongly enhanced echoes.
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 the product are very different from those of soft tissue and will generate strong echoes.
As Luminity consists of microspheres that are stable and small enough for transpulmonary passage, enhanced echo signals in the left heart and systemic circulation are obtained.
A strict dose/response relationship cannot be defined, although higher doses have been shown to produce a contrast effect of longer duration.
The pharmacokinetic properties of Luminity were evaluated in normal healthy subjects and subjects with chronic obstructive pulmonary disease (COPD) following intravenous administration of a
50 µl/kg dose of the product.
The perflutren component of Luminity was rapidly cleared from the systemic circulation via the lungs. The percentage of the perflutren dose excreted in expired air was approximately 50% of the administered dose due to the small quantities of perflutren given and the inability to quantify low levels of perflutren by gas chromatography. In most subjects after
The naturally occurring phospholipids in Luminity (see section 6.1) are distributed in the endogenous lipid pools in the body (for example, liver) whereas the synthetic component (MPEG5000) has been shown to be excreted in the urine in preclinical studies. All lipids are metabolised to free fatty acids. The pharmacokinetics and metabolism of MPEG5000 DPPE have not been evaluated in humans.
Pharmacokinetics in special population groups
Pharmacokinetics has not been specifically studied in the elderly.
- Sonovue - V08DA04
Prescription drugs listed. ATC Code: "V08DA04"
Pharmacokinetics has not been specifically studied in the renal disease patients.
Pharmacokinetics has not been specifically studied in the hepatic disease patients.
5.3Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of genotoxicity, fertility, embryo/foetal development, parturition or
Abnormal respiration, heart rate changes and decreased activity were observed soon after intravenous injection of Luminity at doses ≥ 0.3 ml/kg in single and
increased goblet cell size and number in the lungs. These effects were observed at exposure levels in excess of the maximum human exposure indicating little relevance to clinical use.
6.1List of excipients
Sodium dihydrogen phosphate monohydrate Disodium hydrogen phosphate heptahydrate Sodium chloride
Propylene glycol Glycerol
Water for injections
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
The product should be used within 12 hours of activation. The product can be
After activation: Do not store above 30°C.
6.4Special precautions for storage
Store in a refrigerator (2°C - 8°C)
For storage conditions after activation of the medicinal product, see section 6.3.
6.5Nature and contents of container
1.5 ml liquid in clear borosilicate Type I glass vial, closed with a chlorobutyl elastomeric lyophilisation stopper, and sealed with an aluminium crimp seal having a plastic
Pack sizes of 1 or 4 vials.
Not all pack sizes may be marketed.
6.6Special precautions for disposal and other handling
It is essential to follow instructions for use and handling of Luminity and to adhere to strict aseptic procedures during preparation. Like all parenteral products, the vials must be inspected visually for particulates and vial integrity. Before administering the product, it must be activated by using the Vialmix, a mechanical shaking device. The Vialmix is not included in the Luminity pack but will be provided to healthcare professionals upon ordering the pack.
Luminity is activated by using the Vialmix which has a programmed shaking time of 45 seconds. The Vialmix will alert the operator if the shaking frequency varies by 5% or more below the target
frequency. It also has been programmed to shut down and will provide visual and audio warnings if the shaking frequency exceeds the target frequency by 5%, or falls below the target frequency by 10%.
Activation process and administration
- The vial should be activated using the Vialmix. Immediately after activation, Luminity appears as a milky white dispersion.
Note: if the product is allowed to stand for more than 5 minutes after activation, it should be resuspended with 10 seconds of hand agitation prior to syringe withdrawal from the vial. Luminity should be used within 12 hours following activation. The product can be
-The vial should be vented with a sterile syringe needle or a sterile
-The dispersion should be withdrawn from the vial using a syringe with a 18 to 20 gauge sterile needle or attached to a sterile
-Luminity may be diluted with sodium chloride 9 mg/ml (0.9%) solution for injection or glucose
50 mg/ml (5%) solution for injection.
The contents of the vial are intended for single use only.
Any unused product or waste material should be disposed of in accordance with local requirements.
7.MARKETING AUTHORISATION HOLDER
Lantheus MI UK Limited
39 Oxford Street
Newbury, Berkshire, RG14 1JG
8.MARKETING AUTHORISATION NUMBER(S)
EU/1/06/361/001 - 002
9.DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 20 September 2006
Date of latest renewal: 15 July 2016
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.