Summary of Product Characteristics (SmPC) - Tauroselcholic Acid (75Se) 370 kBq capsules
1 NAME OF THE MEDICINAL PRODUCT
Tauroselcholic Acid (75Se) 370 kBq capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
[75Se]tauroselcholic acid is supplied as capsules of 370 kBq at the activity reference date.
Each capsule contains less than 0.1mg of tauroselcholic acid.
Selenium-75 has a physical half-life of approximately 118 days and decays by gamma emission with principal energies at 0.136 MeV and 0.265 MeV.
Excipient(s) with known effect
This medicinal product contains:
Sodium: 71.04 mg in each capsule.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Capsule, hard.
Hard, gelatin capsule.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicinal product is for diagnostic use only.
[75Se]tauroselcholic acid is used for the investigation of bile acid malabsorption and measurement of bile acid pool loss. It may be used in the assessment of ileal function, in the investigation of inflammatory bowel disease and chronic diarrhoea and in the study of entero-hepatic circulation.
4.2 Posology and method of administration
Posology
Adult and elderly patients
The normal dose for adults and the elderly is one capsule, administered orally.
Paediatric population
If the product is to be administered to children the same dosage as in adults is used.
There is no paediatric dosage form or clinical experience of the use of this product in children. A careful assessment of the risk/benefit ratio should be undertaken before use of the product in children, particularly since use of a fixed dose results in an increased Effective Dose Equivalent in children (see section 11).
Hepatic impairment
Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.
Method of administration
To ensure smooth passage of the capsule into the stomach, it is recommended that 15ml drinks of water are taken by the patient before, during and after swallowing the capsule. The patient should be in a sitting or standing position during administration.
The instructions for preparation of radiopharmaceuticals are given in section 12.
For patient preparation, see section 4.4.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
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.
Caution is advised in the administration of [75Se]tauroselcholic acid to patients with severe hepatic dysfunction or biliary tract obstruction as in these conditions radiation dose to the liver will be significantly increased.
For each patient, exposure to ionising radiation must be justifiable on the basis of likely benefit. The activity administered must be such that the resulting radiation dose is as low as reasonably achievable bearing in mind the need to obtain the intended diagnostic or therapeutic result.
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.
Hepatic impairment
Careful consideration of the benefit risk ratio in these patients is required since an increased radiation exposure is possible.
Paediatric population
No data are available. Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11).
Specific warnings
This medicinal product contains 3.01 mmol (71.04 mg) sodium in each capsule. This should be taken into account in patients on a low sodium diet.
Precautions with respect to environmental hazard see section 6.6.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed to date.
Bile Acid Sequestrants (BAS)
Bile acid sequestrants (BAS) such as cholestyramine and colesevelam, may interfere with Tauroselcholic Acid (75Se) results. It is recommended that BAS be discontinued for 7 days before the examination with Tauroselcholic Acid (75Se) and resumed after the 7th-day scan.
Clinicians may need to consider symptomatic management, dietary modifications, or alternative therapies (and their combinations) based on relevant treatment guidelines and therapeutic protocols where appropriate during the 14-day period when patients are temporarily discontinuing BAS treatment.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about the potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient.
Pregnancy:
No data are available on the use of this product in human pregnancy. Animal reproduction studies have not been performed.
Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. Only essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds the risk incurred by the mother and the foetus.
Breast-feeding:
Before administering a radioactive medicinal product to a mother who is breast feeding consideration should be given as to whether the investigation could be reasonably delayed until after the mother has ceased breast feeding and as to whether the most appropriate choice of radiopharmaceutical has been made, bearing in mind the secretion of activity in breast milk.
If the administration is considered necessary, breast feeding should be interrupted.
Breast milk should be expressed and discarded about three to four hours after [75Se]tauroselcholic acid administration, after which breast feeding can be resumed.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
4.8 Undesirable effects
The frequencies of undesirable effects are defined as follows:
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) and not known (cannot be estimated from the available data).
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is 0.26 mSv when the maximal recommended activity of 370 kBq is administered these adverse reactions are expected to occur with a low probability.
Immune system disorders
Not known: Hypersensitivity
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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Paediatric population
No data are available.
4.9 Overdose
It is considered that overdosage is unlikely as the product is presented as a capsule which is administered orally in a controlled clinical setting. Should overdosage occur there are no known procedures which could be used to increase the clearance of activity from the body.
Paediatric population
No data are available.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: diagnostic radiopharmaceuticals, hepatic and reticulo endothelial system, selenium (75Se) tauroselcholic acid, ATC Code: V09DX01
Mechanism of action
Tauroselcholic acid is a bile acid analogue which shows identical physiological behaviour with naturally occurring bile acid conjugates.
Pharmacodynamic effects
At the chemical concentrations and activities used for diagnostic procedures [75Se]tauroselcholic acid does not appear to exert any pharmacodynamic effects.
Clinical efficacy and safety
See Pharmacodynamic effects.
Paediatric population
No data are available.
5.2 Pharmacokinetic properties
Distribution
The distribution of activity is almost entirely confined to the lumen of the biliary ducts, gut and liver.
Organ Uptake
Following oral administration in normal subjects, approximately 95% of the labelled bile acid is absorbed, mainly by the terminal ileum during each enterohepatic cycle.
Elimination
See Half-life.
Half-life
Whole body retention data from normal subjects showed 97 to 100% of [75Se]tauroselcholic was excreted with a biological half-life of 2.6 days and that, in most cases, a small component of about 3% was eliminated with a mean half time of 62 days.
Paediatric population
No data are available.
5.3 Preclinical safety data
A single dose study in rats has indicated a safety margin of greater than 10,000 times the maximum human oral dosage. This agent is not intended for regular or continuous administration. Repeat dose toxicity studies, mutagenicity and long-term carcinogenicity studies have not been performed.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Disodium phosphate dihydrate
Gelatin capsule
The gelatin capsule contains the following ingredients:
Titanium dioxide
Quinoline yellow
Erythrosine
Gelatin
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
The shelf life for this product is 18 weeks from the date of manufacture. The activity reference date is 12 weeks before expiry.
6.4 Special precautions for storage
Store below 25°C. Do not freeze. Protect from light.
Store in accordance with national regulations for radioactive materials.
6.5 Nature and contents of container
Tauroselcholic Acid (75Se) is available in polystyrene containers with polythene caps. The capsules are held in place with polyether foam pads.
Pack size: single capsule packs.
6.6 Special precautions for disposal and other handling
General warning
Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licenses of the competent official organisation.
Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.
If at any time in the preparation of this product the integrity of this container is compromised it should not be used.
Administration procedures should be carried out in a way to minimise risk of contamination of the medicinal product and irradiation of the operators. Adequate shielding is mandatory.
The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill of urine, vomiting, etc. Radiation protection precautions in accordance with national regulations must therefore be taken.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
GE Healthcare Limited
Pollards Wood
Nightingales Lane
Chalfont St Giles
Buckinghamshire HP8 4SP
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 00221/0105
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of first authorisation: 07 January 2002
Date of last renewal: 20 April 2006
10 DATE OF REVISION OF THE TEXT
14/01/2026
11 DOSIMETRY
The table below shows the dosimetry as calculated according to the Publication 80 of the ICRP (International Commission on Radiological Protection, Radiation Dose to Patients from Radiopharmaceuticals, Pergamon Press 1998).
| Absorbed dose per unit activity administered (mGy/MBq) | |||||
| Organ | Adult | 15 years | 10 years | 5 years | 1 year |
| Adrenals | 3.2E-01 | 4.1E-01 | 6.2E-01 | 9.4E-01 | 1.5E+00 |
| Bladder | 3.3E-01 | 4.2E-01 | 6.7E-01 | 1.0E+00 | 1.7E+00 |
| Bone surfaces | 2.3E-01 | 3.0E-01 | 4.3E-01 | 6.4E-01 | 1.2E+00 |
| Brain | 4.8E-02 | 5.6E-02 | 7.9E-02 | 1.2E-01 | 2.0E-01 |
| Breast | 7.7E-02 | 9.6E-02 | 1.8E-01 | 2.8E-01 | 5.2E-01 |
| Gall bladder | 6.4E+00 | 7.1E+00 | 9.0E+00 | 1.5E+01 | 4.8E+01 |
GI-tract Stomach SI Colon ULI LLI | 4.2E-01 1.9E+00 2.0E+00 1.9E+00 2.1E+00 | 5.5E-01 2.4E-+00 2.4E-+00 2.3E-+00 2.6E-+00 | 9.3E-01 3.8E+00 3.8E+00 3.5E+00 4.2E-00 | 1.5E+00 5.9E+00 5.8E+00 5.3E+00 6.5E+00 | 2.5E+00 1.0E+01 1.0E+01 9.1E+00 2.1E+01 |
| Heart | 3.3E-01 | 4.3E-01 | 6.4E-01 | 9.6E-01 | 1.6E+00 |
| Kidneys | 5.0E-01 | 6.1E-01 | 8.9E-01 | 1.3E+00 | 2.0E+00 |
| Liver | 6.9E-01 | 8.7E-01 | 1.3E+00 | 1.8E-00 | 3.2E+00 |
| Lungs | 2.4E-01 | 3.3E-01 | 4.7E-01 | 7.2E-01 | 1.3E+00 |
| Muscles | 2.0E-01 | 2.5E-01 | 3.7E-01 | 5.5E-01 | 9.8E-01 |
| Oesophagus | 1.1E-01 | 1.4E-01 | 1.9E-01 | 2.9E-01 | 4.8E-01 |
| Ovaries | 1.0E+00 | 1.3E+00 | 2.0E+00 | 2.9E+00 | 4.9E+00 |
| Pancreas | 4.5E-01 | 5.8E-01 | 1.1E+00 | 1.7E+00 | 2.6E+00 |
| Red marrow | 2.9E-01 | 3.4E-01 | 4.6E-01 | 6.0E-01 | 8.3E-01 |
| Skin | 7.5E-02 | 9.1E-02 | 1.4E-01 | 2.2E-01 | 4.2E-01 |
| Spleen | 3.0E-01 | 4.1E-01 | 6.6E-01 | 1.0E+00 | 1.7E+00 |
| Testes | 9.2E-02 | 1.3E-01 | 2.2E-01 | 3.7E-01 | 7.0E-01 |
| Thymus | 1.1E-01 | 1.4E-01 | 1.9E-01 | 2.9E-01 | 4.8E-01 |
| Thyroid | 6.9E-02 | 9.6E-02 | 1.5E-01 | 2.7E-01 | 5.2E-01 |
| Uterus | 7.5E-01 | 9.4E-01 | 1.5E+00 | 2.3E+00 | 3.8E+00 |
| Remaining Organs | 2.6E-01 | 3.4E-01 | 5.3E-01 | 8.3E-01 | 1.3E+00 |
| Effective Dose (mSv/MBq) | 6.9E-01 | 8.6E-01 | 1.3E+00 | 2.0E+00 | 3.9E+00 |
For this product the Effective Dose to a healthy adult resulting from the administration of a 370 kBq capsule is typically 0.26mSv.
In most clinical investigations for which this substance is used (e.g. Crohn's disease) the effects of impaired ileal absorption and shorter gastrointestinal transit time tend to reduce the dose commitment compared with the normal case. However, in patients with severe cholestatic jaundice, the liver dose has been estimated to be about 100 times the normal value.
12 INSTRUCTIONS FOR PREPARATION OF
RADIOPHARMACEUTICALS
PROCEDURE FOR USE
Measurement of bile pool loss
Measurement of the rate of bile loss from the endogenous pool using Tauroselcholic Acid (75Se) may be achieved either by determining the retention of activity in the body over a period of days or by determining the excretion of activity in faeces. The results may be expressed as a rate of loss if several measurements are taken, or more simply as a retained percentage after a fixed period (7 days is convenient). A whole body counter or other counter or other counting techniques may be used. For some investigations scintigraphic studies may be appropriate.
Measurement of retained activity whole body counter
A 370 kBq (10 μCi) capsule is administered to the patient together with a drink of water. Using conventional whole body counting techniques an initial count of the patient provides, after background subtraction, a zero- time or 100% value. After 7 days the patient is counted again, and the retained activity expressed as a percentage of the original value.
Alternative techniques
If a whole body counter is not available, other counting techniques may be used successfully. Since the activity is confined to the abdominal region, a counter with a field of view encompassing the abdomen can be employed.
A gamma camera is used extensively and single crystal probes have also been used. A gamma camera with its collimator removed has proved successful and is the most commonly used technique. Collimated cameras have also shown to be useful. However, the use of this technique may require an increase in acquisition time to reduce uncertainties in Tauroselcholic Acid (75Se) retention measurements.
A standard axial positioning of the patient along the centreline of the counter should be maintained. The centre of the crystal should be positioned midway between the umbilicus and the base of the sternum.
To avoid excessive background interference from sources of technetium-99m, it is recommended that the camera window be set at the 265 keV photon peak of selenium-75 (20% window).
It is important that same technique is used at day 0 and day 7 to avoid any errors in the final calculation of the retention rate.
It is also important to keep the positioning of the patient constant at each measurement.
Procedure
- 1. The patient should be given at least 15 ml of water to drink prior to taking the capsule. A similar drink of water should be taken with the capsule and again afterwards to encourage rapid transit of the capsule to the stomach and subsequent dispersion of the contents.
- 2. Allow 1-3 hours for physiological equilibration.
- 3. Measure the background before the first count of the patient. A preset time may be used.
- 4.
Place the patient on the couch as described above. AP Count for preset time
(300 seconds suggested and record the counts).
- 5. Turn the patient and repeat the count from the other view, PA.
- 6. Measure the background again.
- 7. After background subtraction, calculate the geometric mean of the two patient counts √(PA x AP).
- 8. Repeat steps 3-7 after 7 days.
- 9. Correct the day 7 value for radioactive decay by multiplying by 1.04
- 10. Express day 7 value as percentage of day 0 value.
Measurement of excreted activity
The alternative method of estimating bile acid loss is by scintillation counting of total faecal samples collected over a period (e.g. 7 days). A dosage of 370 kBq (10 μCi) (orange and yellow capsule) is recommended. It is important to ensure that standard geometry is monitored and that total collection of faeces is achieved. Samples from patients undergoing two simultaneous radionuclide is known investigations should not be counted unless faecal excretion of the other radionuclide is known to be insignificant, or unless the counting equipment can be selectively set to accumulate only selenium-75 photon emissions.
Counting of the faecal γ activity using a sodium iodide crystal detector in a well counter or other suitable instrument is the counting method of choice.
The procedure for the administration of the capsule of Tauroselcholic Acid (75Se) is the same as when measuring retained activity.