SUMMARY OF PRODUCT CHARACTERISTICS
for
NanoScan, kit for radiopharmaceutical preparation
1. NAME OF THE MEDICINAL PRODUCT
NanoScan
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Active substance
Human Serum Albumin nano sized colloid 500 micrograms.
At least 95 % of human albumin colloidal particles have a diameter ≤ 80 nm.
NanoScan is prepared from human serum albumin derived from human blood donations tested according to the EEC Regulations and found non reactive for :
- hepatitis B surface antigen (HBsAg)
- antibodies to human immunodeficiency virus (anti-HIV 1/2)
- antibodies to hepatitis C virus (anti-HCV)
The radionuclide is not part of the kit.
Excipient(s)
Sodium: 0.045 mmol.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Kit for radiopharmaceutical preparation.
White powder.
Powder for solution for injection.
To be reconstituted with sodium pertechnetate (99mTc) solution for injection.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.
After radiolabelling with sodium (99mTc) pertechnetate solution for injection the solution obtained is indicated in:
· Bone marrow scanning (The product is not suitable to study the haematopoietic activity of the bone marrow)
· Inflammation scanning in areas other than the abdomen
· Conventional lymphoscintigraphy to demonstrate integrity of the lymphatic system and differentiation of venous from lymphatic obstruction
· Sentinel node detection in:
o Melanoma malignum
o Breast cancer
4.2 Posology and method of administration
Posology
Recommended activities in adults are as follows:
- Bone marrow scanning: 185-500 MBq as a single intravenous injection.
- Inflammation scanning: 370-500 MBq as a single intravenous injection.
- Conventional lymphoscintigraphy: The recommended activity by single or multiple subcutaneous injection ranges from 18.5 - 110 MBq per injection site and depends on the anatomical areas to be investigated and upon the time interval between injection and imaging. The injected volume should not exceed 0.2 - 0.3 ml. A maximum volume of 0.5 ml per injection is critical.
- Sentinel node detection:
- Malignant Melanoma: Total activity applied 40 – 100MBq by single or multiple injection. Other activities can be used in special circumstances and/or conditions. The volume per injection should be 0.05 – 0.2 ml. At least 4 injections should be made using an aliquot of the suggested total activity. The injection should be made intradermally or peritumoral
- Breast Cancer: Total activity applied 100 – 200MBq by single or multiple injection. Other activities can be used in special circumstances and/or conditions. The injected activity varies depending on the time elapsed between the scintigraphic imaging and surgery. The volume per injection should be 0.2 – 1.0 ml. The injection should be made as 1 application when using subdermal and/or subareolar technique and 4 applications should be made when applied peritumoral and/or circum areolar.
4.2.2 Pediatric doses
The use in paediatric children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefit ratio in this patient group. The activities to be administered to children and to adolescents may be calculated according to recommendations of the Paediatric Task Group of EANM from the body weight according to the following table.
Fraction of adult dose:
3 kg = 0.10 / 22 kg = 0.50 / 42 kg = 0.784 kg = 0.14 / 24 kg = 0.53 / 44 kg = 0.80
6 kg = 0.19 / 26 kg = 0.56 / 46 kg = 0.82
8 kg = 0.23 / 28 kg = 0.58 / 48 kg = 0.85
10 kg = 0.27 / 30 kg = 0.62 / 50 kg = 0.88
12 kg = 0.32 / 32 kg = 0.65 / 52-54 kg = 0.90
14 kg = 0.36 / 34 kg = 0.68 / 56-58 kg = 0.92
16 kg = 0.40 / 36 kg = 0.71 / 60-62 kg = 0.96
18 kg = 0.44 / 38 kg = 0.73 / 64-66 kg = 0.98
20 kg = 0.46 / 40 kg = 0.76 / 68 kg = 0.99
In very young children (up to 1 year) a minimum dose of 20 MBq (bone marrow scanning) is necessary in order to obtain images of sufficient quality.
Method of administration:
This medicinal product should be reconstituted before administration to the patient. For instructions on reconstitution of the medicinal product before administration, see section 12.
This agent is not intended for regular or continuous administration.
Image acquisition
· Bone marrow scanning: Images may be acquired 45-60 minutes after administration.
· Inflammation scanning: Dynamic imaging is performed immediately. Static imaging comprises an early phase, 15 minutes post-injection and a washout phase, 30-60 minutes post-injection.
· Conventional lymphoscintigraphy: The injection is given subcutaneously, after checking by aspiration, that a blood vessel has not been inadvertently punctured. When imaging the lower limbs, dynamic pictures are taken immediately following injection and static imaging 30-60 minutes later. In parasternal lymph scanning, repeated injections and additional images may be required.
· Sentinel node detection:
- Malignant Melanoma: Lymposcintigraphic images are obtained starting after injection and regularly thereafter until the SLN is visualized.
- Breast Cancer: Scintigraphic scans of breast and axillary region can be acquired 15-30 min and 3 hours after injection.
4.3 Contraindications
Hypersensitivity to the active substance(s), to any of the excipients or to any of the components of the labelled radiopharmaceutical. In particular, the use of 99mTc-human albumin colloidal particles is contra-indicated in persons with a history of hypersensitivity to products containing human albumin.
During pregnancy, lymphoscintigraphy involving the pelvis is strictly contraindicated due to the accumulation in lymph nodes.
4.4 Special warnings and precautions for use
Pregnancy, see section 4.6.
The preparation without reconstitution with sodium 99mTc-pertechnetate must not be administered to patients.
Potential for hypersensitivity or anaphylactic reactions
If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must be immediately available.
Individual benefit/ risk justification
For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information.
It cannot be administered to pregnant or lactating mothers or patients less than 18 years of age except when the value of the desired clinical information exceeds the risk of the radiation burden incurred by the patient. With women of child- bearing potential, the investigation should be performed during the first 10 days after the onset of menses.
Paediatric population
For information on the use in paediatric population, see section 4.2. or 5.1.
Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).
Adolescents, see section 4.2.
It is strongly recommended that the product name and batch number are stated every time Tc- albumin nanocolloid is given to a patient, in order to maintain a connection between the patient and the products batch number.
Standard measures for preventing transmission of infections from pharmaceuticals made of human blood or plasma, include selection of donators, test of individual donators and plasma pools for finding specific infective agents, and effective manufacturing steps for inactivation/elimination of virus as a part of manufacturing process as well. In spite of that, the risk of transmission of infectious agents cannot be eliminated completely, as long as pharmaceuticals made of human blood or plasma are used. This also applies to new virus of unknown nature and other pathogens as well.
There are no reports of virus transmission in connection with albumin, made in accordance with specifications in Ph. Eur. and in accordance with routine processes.
Lymphoscintigraphy is not advised in patients with total lymphatic obstruction because of the potential radiation hazard at injection sites. The subcutaneous injection must be made without pressure into loose connective tissue.
Precautions with respect to environmental hazard are in section 6.6.
The human albumin contained in Nanoscan corresponds to the requirements "Note for Guidance on Plasma Derived Products", CPMP/BWP/269/95, rev. 2. For the production of NanoScan only human albumin of plasma of donators was used whose blood on the occasion of every donation was checked individually with suitable methods for HBsAg and antibody against HIV-1, HIV-2 and HCV and was found not reactive. Blood or plasma of donators from a land in which several cases vCJK have appeared is not used for the production of the human albumin.
Patient preparation
The patient should be well hydrated before the start of the examination and urged to void as often as possible during the first hours after the study in order to reduce radiation.
Specific warnings
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
Interaction studies have only been performed in adults.
Iodinated contrast media used in lymphoangiography may interfere with lymphatic scanning using 99mTc-NanoScan.
4.6 Pregnancy and lactation
Women of childbearing potential
When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. Where uncertainty exists, it is important that radiation exposure should be the minimum consistent with achieving the desired clinical information. Alternative techniques, which do not involve ionising radiation should always considered.
Pregnancy
The subcutaneous administration of 99mTc-NanoScan for lymphoscintigraphy is strictly contraindicated during pregnancy due to the possible accumulation in pelvic lymph nodes.
Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus. Only imperative investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and foetus. An intravenous dose of 500 MBq of 99mTc-NanoScan, gives rise to an estimated uterus exposure of 0.9 mGy. An uterus exposure above 0.5 mGy is regarded as a potential risk to the foetus.
Breast-feeding
Before administering radiopharmaceuticals to a mother who is breast-feeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 13 hours and the expressed feeds discarded.
4.7 Effects on ability to drive and use machines
NanoScan has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
The following table presents how the frequencies are reflected in this section:
Very common (³1/10)
Common (³1/100 to <1/10)
Uncommon (³1/1,000 to <1/100)
Rare (³1/10,000 to <1/1,000)
Very rare (<1/10,000), not known (cannot be estimated from available data)
Congenital, familial and genetic disordersFrequency not known (cannot be estimated from the available data) / Hereditary defects
Neoplasms benign, malignant and unspecified (including cysts and polyps)
Frequency not known (cannot be estimated from the available data) / Cancer induction
Immune system disorders
Rare
Frequency not known (cannot be estimated from the available data). / Protein allergic (hypersensitive) reaction
Hypersensitivity reactions (including
very rare life-threatening anaphylaxis)
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 2.3 mSv when the maximal recommended activity of 500 MBq is administered these adverse events are expected to occur with a low possibility.
When a protein-containing radiopharmaceutical such as 99mTc-NanoScan is administered to a patient, hypersensitivity reactions may develop.
Adequate medication and reanimation equipment must therefore always be kept available during the investigation.
For safety with respect to transmissible agents see section 4.4.
4.9 Overdose
The risk of overdose lies in an unintentional high exposure to ionising radiation.
In the event of an overdose of radioactivity being administered when using 99mTc albumin nanocolloid, no practical measure can be recommended to satisfactorily diminish tissue exposure as the label is poorly eliminated in urine and faeces.
4.10 Udlevering
BEGR – kun til sygehuse.
5. PHARMACOLOGICAL PROPERTIES
5.0 Terapeutisk klassifikation
ATC code: V 09 DB 01. Technetium (99mTc), particles and colloids.
5.1 Pharmacodynamic properties
At the chemical concentrations and activities used for diagnostic procedures 99mTc-NanoScan does not appear to exert any pharmacodynamic effects.
5.2 Pharmacokinetic properties
The NanoScan colloidal product produced from human serum albumin consists of particles in 95 %, below 80 in size.
Reticuloendothelial cells in liver, spleen as well as in bone marrow are responsible for blood clearance after intravenous injection. A small fraction of 99mTc radioactivity passes through kidneys and is eliminated in urine.
The maximum concentration in the liver and spleen is reached after about 30 minutes, but in the bone marrow after only 6 minutes.
The proteolytic breakdown of the colloid begins immediately after its uptake by the RES, the products of degradation being excreted through the kidneys into the bladder.
After subcutaneous injection into connective tissue, 30-40 % of the administered 99mTc-NanoScan (colloidal particles in 95 %, below 80 nm) are filtered into lymphatic capillaries whose main function is the drainage of proteins from the interstitial fluid back into the blood pool.
The 99mTc-albumin colloidal particles are then transported along the lymphatic vessels to regional lymph nodes and main lymphatic vessels, and are finally trapped into the reticular cells of functionary lymph nodes. A fraction of the injected dose is phagocytized by histiocytes at the injection site. Another fraction appears in the blood and accumulates mainly in the RES of the liver, spleen and bone marrow; faint traces are eliminated via the kidneys.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humansbased on studies of single-dose toxicity.
Studies of genotoxicity, carcinogenicity and toxicity to reproduction have not been performed.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Stannous(II) Chloride dihydrate
Glucose