Download 1. name of the medicinal product

27 May 2016
SUMMARY OF PRODUCT CHARACTERISTICS
for
CAPSION, capsules
1.
NAME OF THE MEDICINAL PRODUCT
CAPSION
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 50 to 3,700 MBq sodium iodide (131I) at calibration date.
Iodine-131 is produced by fission of uranium-235 and by neutron bombardment of stable
tellurium in a nuclear reactor. Iodine-131 has a half-life of 8.04 days. It decays by emission
of gamma radiation of 365 keV (81.2 %), 637 keV (7.3 %) and 284 keV (6.1 %) and βradiations of maximal energy of 606 keV to stable xenon-131.
Excipient with known effect:
Each capsule contains 110 mg of sodium.
For a full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Capsule hard.
Capsule green and orange.
4.
CLINICAL PARTICULARS
4.1. Therapeutic indications
Radioiodine thyroid therapy is indicated for:
 Treatment of Graves’ disease, toxic multinodular goitre or autonomous nodules.
 Treatment of papillary and follicular thyroid carcinoma including metastatic disease.
Sodium iodide (131I) therapy is often combined with surgical intervention and with
antithyroid medications.
4.2. Posology and method of administration
Posology
The activity administered is a matter for clinical judgment. The therapeutic effect is only
achieved after several weeks.
769844076
Page 1 of 17
- For the treatment of hyperthyroidism:
Patients should be rendered euthyroid medically whenever possible before giving
radioiodine treatment for hyperthyroidism. The dose required depends on the diagnosis, the
size of the gland, thyroid uptake and iodine clearance.
The range of activities currently prescribed, irrespective of the method used, vary in the
range 200–800 MBq, but repeated treatment may be necessary. Re-treatment after
six months is indicated for persisting hyperthyroidism.
The activity administered depends on the diagnosis, the size of the gland, thyroid uptake,
and iodine clearance. The following target organ doses may be used:
•
•
•
unifocal autonomy :
300-400 Gy target organ dose
multifocal and disseminated autonomy : 150-200 Gy target organ dose
Graves`disease :
200 Gy target organ dose
In Graves’ disease, multifocal or disseminated autonomy, the above mentioned target organ
doses are related to the overall volume of the thyroid gland, however in the unifocal
autonomy, the target organ dose is only related to the volume of the adenoma.
The activity to be administered may be calculated according to the following equation:
Target dose (Gy) x target volume (ml)
A (MBq) = ___________________________________________________
max. uptake 131I (%) x effective T ½ (days)
xK
Legend:
target dose
=
is the target absorbed dose in the whole thyroid gland or in
an adenoma
volume of the whole thyroid gland (Graves’ disease,
multifocal or disseminated autonomy)
target volume
=
max. uptake I-131
=
max. uptake of I-131 in the thyroid gland or nodules in % of
the administered activity as established in a test dose
effective T ½
=
effective half-life of I-131 in the thyroid gland
K
=
24.67
Other dosimetric procedures may also be used including sodium pertechnetate (Tc-99m)
thyroid uptake tests to determine the appropriate target organ dose (Gy).
Fixed dose protocols may also be used.
- For thyroid ablation and treatment of metastases
The administered activities following total or subtotal thyroidectomy to ablate remaining
thyroid tissue are in the range of 1,850 – 3,700 MBq. It depends on the remnant size and radioiodine uptake. In subsequent treatment for metastases, administered activity is in the
range 3,700 – 11,100 MBq.
769844076
Page 2 of 17
Renal impairment
Careful consideration of the activity to be administered is required since an increased
radiation exposure is possible in these patients.
An adjustment of the posology should be considered.
Paediatric population
The use in children and adolescents has to be considered carefully, based upon clinical
needs and assessing the risk/benefit ratio in this patient group.
The activity to be administered in children and adolescents should be determined after
performing an individual dosimetry (see sections 4.4 and 11).
Method of administration
Oral use.
For patient preparation, see section 4.4.
The capsule should be taken orally by the fasting patient. It should be swallowed whole
together with plenty of liquid. It must be ensured that the patient drinks sufficient amounts
of liquid.
To ease the passage of the capsule through the oesophagus and subsequently create the right
climate for the capsule to dissolve in, it is recommended to the patient to take hot drink,
rapidly after the administration.
Before giving the capsule to children, in particular to young children, it should be ensured
that the capsule can be swallowed whole.
4.3. Contraindications
 Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
 Pregnancy (see section 4.6).
 Breastfeeding (see section 4.6).
 Patients with dysphagia, oesophageal stricture, untreated oesophageal stenosis, oesophagus
diverticulum, active gastritis, gastric erosions and peptic ulcer.
 Patients with suspected reduced gastrointestinal motility (see section 4.4).
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.
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 therapeutic effect.
Renal impairment
Careful consideration of the benefit/risk ratio in these patients is required since an increased
radiation exposure is possible. The therapeutic administration of sodium iodide (131I)
capsules in patients with significant renal impairment, in which an activity adjustment is
necessary, requires special attention.
769844076
Page 3 of 17
Paediatric population
Careful consideration of the indication is required since the effective dose per MBq is higher than in adults (see section 11). In the treatment of children and adolescents, the radioiodine treatment of benign thyroid diseases may be performed in justified cases, especially in
relapse after use of anti-thyroid medicinal products or when serious adverse reactions to anti-thyroid medicinal products do occur. There is little evidence of an increased incidence of
cancer, leukemia or mutations in man with respect to patients treated for benign thyroid disease with radioiodine, despite extensive use. In the treatment of children and young people
however, account must be taken of the greater sensitivity of child tissue and the greater life
expectancy of such patients. The risks must also be weighed against those of other possible
treatments (see section 4.2 and 11).
Patient preparation
A low iodine diet prior to therapy will enhance uptake into functioning thyroid tissue.
Patients should be encouraged to increase oral fluids and urged to void as often as possible
to reduce bladder radiation, especially after high activities e.g. for radionuclide therapy.
Patients with bladder voiding problems should be catheterised after high activity
administration.
After the procedure
To reduce radiation exposure of the salivary glands and avoid sialadenitis which may
complicate high dose radioiodine administration, the patient may be advised to take sweets
or drinks containing citric acid which will stimulate saliva excretion.
To reduce colon exposure, laxatives (but not stool softeners which do not stimulate the
bowel) may be necessary in patient having less than one bowel movement a day.
The patient should be followed-up at appropriate intervals.
For radioprotection reasons, close contact with infants and pregnant women must be
restricted. The period of close contact restriction should be adapted to the administered
activity and the type of pathology.
Specific warnings:
Thyroid replacement should be stopped prior to radioiodine administration for thyroid
carcinoma to ensure adequate uptake. A period of fourteen days is recommended for
triiodothyronine and four to five weeks for thyroxine. They should be restarted two days
after treatment.
Similarly carbimazole and propylthiouracil should be stopped five days prior to treatment of
hyperthyroidism and possibly restarted several days later.
Sperm banking should be considered for men who have extensive disease (see section 4.6).
Breastfeeding women must be advised to discontinue breastfeeding for 6-8 weeks before
radioiodine administration (see section 4.6.).
In patients with suspected gastrointestinal disease, great care should be taken when
administering sodium iodide (131I) capsules. It must be ensured that the patient drinks
sufficient amounts of fluid to ensure clear passage into the stomach and upper small
intestine. Concomitant use of H2 antagonists or proton pump inhibitors is advised in order
to address the possible gastrointestinal reactions.
769844076
Page 4 of 17
Patients with eye symptoms to be treated for Graves’ disease, should to be treated
concomitantly with corticosteroids
This preparation is likely to result in a relatively high radiation dose to most patients (see sections 4.8 and 11).
The administration of high dose radioiodine may result in significant environmental hazard.
This may be of concern to the immediate family of those individuals undergoing treatment
or the general public depending on the level of activity administered. Suitable precautions in
accordance with national regulations should be taken concerning the activity eliminated by
the patients in order to avoid any contaminations.
There is little evidence of an increased incidence of cancer, leukaemia or mutations in man
with respect to patients treated for benign thyroid disease with radioiodine, despite extensive
use. In the treatment of children and young people, however, account must be taken of the
greater sensitivity of child tissue and the greater life expectancy of such patients.
The risks must also be weighed up against those of other possible treatments. In the treatment
of malignant thyroid disease, a higher incidence of bladder cancer has been reported in one
study of patients receiving more than 3,700 MBq of iodide (131I). Another study has reported a
small excess leukaemia in patients receiving very high doses. A cumulative total activity
higher than 26,000 MBq is therefore not advisable.
In patients with a known hypersensitivity for gelatine or their metabolites, sodium iodide
(131I) solution should be preferred for the radioiodine therapy.
Warning related to excipient:
This medicinal product contains 110 mg of sodium per capsule which has to be taken into
account in patients on 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
Many pharmacological agents are known to interact with radioiodide. This may happen by a
variety of mechanisms which can affect the protein binding, the pharmacokinetics or
influence the dynamic effects of labelled iodide. It is therefore necessary to take a full drug
history and ascertain whether any medications are required to be withheld prior to the
administration of sodium iodide (131I).
769844076
Page 5 of 17
For example, the treatment with the following substances should be discontinued:
Active substances
Period of withhold before
administration of131-iodine
Antithyroid agents (e.g. carbimazole, or other
imidazole derivatives such as propylthiouracil)
and perchlorate
Salicylates, steroids, sodium nitroprusside,
sodium sulfobromophthalein, anticoagulants,
antihistamines, antiparasitics, penicillins,
sulphonamides, tolbutamide, thiopentone
1 week before starting treatment till
several days after.
Phenylbutazone
1 - 2 week(s).
Containing iodine expectorants and vitamins
approx. 2 weeks.
Thyroid hormone preparations
Amiodarone*, benzodiazepines, lithium
Triiodothyronine 2 weeks.
Thyroxine 4-5 weeks
approx. 4 weeks.
Containing iodine preparations for topical use
1 - 9 months.
Containing iodine contrast media
up to 1 year.
1 week.
* Due to the long half-life of amiodarone, iodine uptake in the thyroid tissue can be
decreased for several months.
4.6. 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
her 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.
Women receiving sodium iodide (131I) should be advised NOT to become pregnant within
6-12 months of administration.
Contraception in males and females
Women are advised to use contraception for a time period of 6 -12 months.
As a precaution, men should not father a child for a time period of 6 months after
radioiodine treatment to allow the replacement of irradiated by non-irradiated spermatozoa.
Pregnancy
Sodium iodide (131I) is contraindicated during established or suspected pregnancy or when
pregnancy has not been excluded due to the fact that the absorbed dose to the uterus for this
agent is likely to be in the range 11-511 mGy, and foetal thyroid gland avidly concentrates
iodine during the second and third trimesters (see section 4.3).
Should differentiated thyroid carcinoma be diagnosed during pregnancy, radioactive iodine
treatment must be postponed until after the pregnancy.
769844076
Page 6 of 17
Breastfeeding
Before administering a radiopharmaceutical to a mother who is breastfeeding, 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 must be discontinued for 6-8 weeks
before radioiodine administration in order to ensure that lactation-associated increase in
breast sodium iodide symporter activity has returned to normal. Breastfeeding must not be
resumed after sodium iodide-131 therapy. Breastfeeding can be safely undertaken after
future pregnancy.
Close contact with infants must be restricted. The period of close contact restriction should
be adapted to the administered activity and the type of pathology.
Fertility
A potential transient impairment of gonadal function by high radioiodine therapeutic dose
can be observed in male and female (see section 4.4).
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 reported adverse reactions were derived from the medical literature. The
safety profile of sodium iodide I-131 differs widely according to the doses administered,
while the doses to be administered are dependent on the type of treatment (i.e. treatment of
benign or malignant disease). Moreover, the safety profile depends on the cumulative doses
administered and the dosing intervals which are used.
The following table presents how the frequencies are reflected in this section:
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)
MedDRA Body system
SOCs
Neoplasms benign,
malignant and unspecified
(incl. cysts and polyps)
Blood and lymphatic system
disorders
769844076
Preferred term
Gastric cancer
Bladder cancer
Leukaemia
Breast cancer
Cancer induction
Leukocytosis
Bone Marrow Failure
Thrombocytopenia
Erythrocytopenia
Frequency
Not known
Common
Not known
Page 7 of 17
Immune system disorders
Endocrine disorders
Nervous system disorders
Eye disorders
Respiratory, thoracic and
mediastinal disorders
Gastrointestinal disorders
Reproductive system and
breast disorders
Congenital, familial and
genetic disorders
General disorders and
administration site
conditions
Anaphylactoid reaction
Hypothyroidism
Thyroiditis
Basedow’s disease
Endocrine ophthalmopathy
Hypoparathyroidism
Hyperthyroidism
Thyrotoxic crisis
Brain oedema
Dry eye
Dacryostenosis acquired
Lacrimal disorders
Eye disorders
Pulmonary fibrosis,
Pneumonia,
Respiratory distress
Dyspnoea
Tracheal stenosis
Tracheitis
Salivary gland enlargment
Salivary gland pain
Sialoadenitis
Vomiting
Nausea
Gastrointestinal disorders
Ageusia, dysgeusia
Dry mouth
Tooth loss
Infertility male, azoospermia,
infertility female, menstrual
disorder, ovarian failure
Hereditary disorder
Congenital hypothyroidism
Localised oedema
Discomfort
Pain
Fatigue
Not known
Very common
Common
Uncommon
Not known
Not known
Very common
Uncommon
Not known
Very common
Not known
Not known
Not known
Not known
Early consequences
Some cases of adverse reactions have been reported following the administration of sodium
iodide (131I), including nausea, vomiting and unspecified possible allergic phenomena.
Nausea and vomiting are more frequent after administration by oral route especially after
therapeutic doses and the risks of contamination following the occurrence of vomiting have
to be considered.
Some cases of allergoid reactions following the administration of sodium iodide (131I) have
been reported (European system for reporting of adverse reactions and drug defects). These
reactions are most probably related to hypersensitivity against the gelatine of the capsules or
their metabolites.
769844076
Page 8 of 17
Therapeutic quantities of sodium iodide (131I) may worsen existing hyperthyroidism
temporarily. In the course of a toxic multinodular goitre treatment, (131I) may induce Graves'
disease or thyroid associated ophtalmopathy (incidence 1 to 5 %). This side effect has been
reported in a single case of differentiated thyroid cancer.
High levels of radioactivity may lead to gastrointestinal disturbance usually within the first
hours or days after administration. The incidence of gastrointestinal upset can be as high as
67 %. This can easily be prevented or counteracted by means of symptomatic treatment.
With high dose radioiodine treatment, 1-3 days after administration, the patient may
experience transient inflammatory thyroiditis (and tracheitis), with a possibility of severe
tracheal constriction, especially where there is existing tracheal stenosis.
Sialadenitis may occur, with swelling and pain in the salivary glands, partial loss of taste
and dry mouth. Incidence varies from 10 % (with precautions) and 60 % (without
precautions). Sialadenitis is usually reversible spontaneously or with anti-inflammatory
treatment but cases have occasionally been described of dose-dependent persistent loss of
taste and dry mouth, followed by loss of teeth. The radiation exposure of the salivary glands
should be reduced by stimulating saliva excretion with acidic substances.
The destruction of thyroid follicles caused by the radiation exposure of sodium iodide (I131) may lead to exacerbation of an already existing hyperthyroidism or even to thyrotoxic
crisis.
Malfunction of the lacrimal glands such as ocular dryness and nasolacrimal duct obstruction
may occur after radioiodine treatment. Although these symptoms are in the majority of
cases transient, they may persist for a longer period or appear late in some patients.
High levels of uptake of radioiodine given to the patients can be associated with local pain,
discomfort and oedema in the tissue taking up the radionuclide.
After radioiodine therapy of thyroid carcinoma, a dose dependent impairment of fertility
may occur in men and women.
Radiation induced pneumonia and pulmonary fibrosis have been observed in patients with
diffuse pulmonary metastases from differentiated thyroid carcinoma, due to destruction of
metastatic tissue. This occurs mainly after high dose radioiodine therapy.
In the treatment of metastasizing thyroid carcinomas with CNS involvement, the possibility
of local cerebral oedema and/or an increasing existing cerebral oedema must also be born in
mind.
Late consequences
Dose dependent hypothyroidism may occur as a late consequence of radioiodine treatment
of hyperthyroidism. This may manifest itself weeks or years after treatment, requiring
suitable timed measurement of thyroid function and appropriate thyroid replacement. The
incidence of hypothyroidism, generally not seen until 6-12 weeks, following radioiodine has
been variously reported as between 2-70 %.
Occasionally, cases of transient hypoparathyroidism have been observed after radioiodine;
they must be monitored accordingly and treated with replacement therapy.
769844076
Page 9 of 17
As a late consequence a single administration of over 5,000 MBq or an interval of below
6 months are more likely to be associated with reversible or in very rare cases irreversible
bone marrow depression may develop, with isolated thrombocytopenia or erythrocytopenia,
which may be fatal. Transient leucocytosis is frequently observed.
Epidemiological studies report a higher incidence of stomach cancer in patients receiving
(131I). After higher activities, typically those used in the treatment of thyroid malignancies,
an increased incidence of leukaemia has been observed. There may also be a small increase
in bladder and breast cancers.
Exposure to ionising radiation is linked with cancer induction and a potential for
development of hereditary effects. The radiation dose resulting from therapeutic exposure
may result in higher incidence of cancer and mutations. In all cases it is necessary to ensure
that the risks of the radiation are less than from the disease itself. The effective dose is
284 Sv when the maximal recommended activity of 11,100 MBq is administered and the
thyroid uptake is at 35 %.
Paediatric population
Types of adverse reactions in children are expected to be the same as in adults. Based on
greater radiation sensitivity of child tissue (see section 11) and the greater life expectancy
frequency and severity may be different.
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:
Lægemiddelstyrelsen
Axel Heides Gade 1
DK-2300 København S
Websted: www.meldenbivirkning.dk
E-mail: [email protected]
4.9. Overdose
In the event of administration of a radiation overdose, the absorbed dose to the patient
should be reduced where possible by increasing the elimination of the radionuclide from the
body by frequent micturition and by forced diuresis. Additionally, the blockade of the
thyroid gland should be recommended (e.g. with potassium iodide or perchlorate)
immediately following suspected overexposure in order to reduce the radiation exposure of
the thyroid gland. Emetics can also be given.
5.
PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Radiopharmaceutical product for therapeutic use.
ATC code: V10XA01.
Mechanism of action
The pharmacological active substance is iodine-131 in the form of sodium iodide that is
taken up by the thyroid. It decays mainly there during its long residence time and in this
manner induces a selective irradiation of this organ.
769844076
Page 10 of 17
The  irradiation will dose-dependently decrease cell function and cell division leading to
cell destruction.
Pharmacodynamic effects
Iodide in the amount used for therapeutic indications, is not known to have any
pharmacological effect. More than 90 % of the radiation effects result from β-radiation
which has a mean range of 0.5 mm.
5.2. Pharmacokinetic properties
Absorption
After oral administration sodium iodide (131I) is absorbed rapidly from the upper
gastrointestinal tract (90 % in 60 minutes).
The absorption is influenced by gastric emptying. It is increased by hyperthyroidism and
decreased by hypothyroidism.
Distribution and organ uptake
The pharmacokinetics follows that of unlabelled iodide. After entering the blood stream it is
distributed in the extra thyroidal compartment. From here it is predominantly taken up by
the thyroid or excreted through the kidneys. Small amounts of iodide (131I) are taken up by
salivary glands, gastric mucosa and would also be localised in breast milk, the placenta and
choroid plexus.
Half-life
The effective half-life of radioiodine in plasma is in the order of 12 hours whereas that for
radioiodine taken up by the thyroid gland is about 6 days. Thus after administration of
sodium iodide (131I) approximately 40 % of the activity has an effective half-life of 0.4 days
and the remaining 60 %, 8 days.
Elimination
Elimination is mainly via the urine. Urinary excretion is 37-75 %, faecal excretion is about
10 % with almost negligible excretion in the sweat.
5.3. Preclinical safety data
Because of the small quantities of substance administered compared with the normal food
intake of iodine (40-500 µg/day) no acute toxicity is expected or observed.
There are no data available on the toxicity of repeated doses of sodium iodide nor on its
effects on reproduction in animals or its mutagenic or carcinogenic potential.
6.
PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Anhydrous sodium pyrophosphate
Sodium thiosulphate
Gelatine capsule
upper part: green (titanium dioxide, yellow iron oxide, indigotine)
lower part: orange (titanium dioxide, red iron oxide, yellow iron oxide)
6.2. Incompatibilities
Not applicable.
769844076
Page 11 of 17
6.3. Shelf-life
21 days following manufacture.
The expiry date is indicated on each vial and on the outer packaging.
6.4. Special precautions for storage
Do not store above 25 °C.
Store in the original package.
Storage should be in accordance with national regulations for radioactive material.
6.5. Nature and contents of container
15 ml colourless glass (type I of European Pharmacopoeia) penicillin-type vial, closed with
polypropylene device (centring element and perforator), and sealed with aluminium flip-off
capsule.
Pack size: One capsule from 50 to 3,700 MBq at calibration date per vial.
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 licences 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.
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 capsule is ready for use.
Sodium iodide (131I) capsule is packed in such a way that patients can swallow the capsule
unaided.
It is advised to open the packaging under a ventilated hood.
The activity of the capsule should be checked prior to administration to the patient.
For method of administration, see section 4.2.
The administration of radiopharmaceuticals creates risks for other persons from external
radiation or contamination from spills of urine, vomiting etc. Radiation protection
precautions in accordance with national regulations must therefore be taken.
This preparation is likely to result in a relatively high radiation dose to most patients. The
administration of sodium iodide (131I) may result in significant environmental hazard.
This may be of concern to the immediate family of those individuals undergoing treatment
or the general public depending on the level of activity administered. Suitable precautions in
accordance with national regulations should be taken concerning the activity eliminated by
the patients in order to avoid any contaminations.
Any unused medicinal product or waste material should be disposed of in accordance with
local requirements.
769844076
Page 12 of 17
7.
MARKETING AUTHORISATION HOLDER
CIS BIO international
Route Nationale 306
BP 32
F-91192, GIF-SUR-YVETTE Cedex
France
8.
MARKETING AUTHORISATION NUMBER
DK R. 1174
9.
DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
Date of first authorisation: 26 January 1996
Date of latest renewal: 1 September 2010
10.
DATE OF REVISION OF THE TEXT
27 May 2016
11.
DOSIMETRY
Tabulated radiation dosimetry data, as reported in ICRP publication No 53 (1987), are
reported hereafter.
The ICRP model refers to intravenous administration. Since absorption of radioiodide is
rapid and complete, this model is applicable in case of oral administration also but there is a
further radiation dose to the stomach wall in addition to that due to gastric and salivary
excretion. Assuming that the mean residence time in the stomach is 0.5 hours, the absorbed
dose to the stomach wall increases by about 30 % for (131I) iodine.
Radiation dose to specific organs, which may not be the target organ of therapy, can be
influenced significantly by pathophysiological changes induced by the disease process.
As part of the risk-benefit assessment it is advised that the EDE (Effective Dose Equivalent)
and likely radiations doses to individual target organ(s) be calculated prior to
administration. The activity might then be adjusted according to thyroid mass, biological
half-life and the "re-cycling" factor which takes into account the physiological status of the
patient (including iodine depletion) and the underlying pathology.
769844076
Page 13 of 17
Radiation exposure (Thyroid blocked, uptake 0 %)
Organ
Adrenals
Bladder wall
Bone surfaces
Breast
GI-tract
Stomach wall
Small intest
ULI wall
LLI wall
Kidneys
Liver
Lungs
Ovaries
Pancreas
Red marrow
Spleen
Testes
Thyroid
Uterus
Other tissue
Effective dose equivalent
(mSv/MBq)
Absorbed dose per unit activity administered
(mGy/MBq)
Adult
15 years
10 years
5 years 1 year
0.037
0.042
0.067
0.11
0.20
0.61
0.75
1.1
1.8
3.4
0.032
0.038
0.061
0.097
0.19
0.033
0.033
0.052
0.085
0.17
0.034
0.038
0.037
0.043
0.065
0.033
0.031
0.042
0.035
0.035
0.034
0.037
0.029
0.054
0.032
0.072
0.040
0.047
0.045
0.052
0.080
0.040
0.038
0.054
0.043
0.042
0.040
0.045
0.038
0.067
0.039
0.088
0.064
0.075
0.070
0.082
0.12
0.065
0.060
0.084
0.069
0.065
0.065
0.075
0.063
0.11
0.062
0.14
0.10
0.12
0.12
0.13
0.17
0.10
0.096
0.13
0.11
0.10
0.10
0.12
0.10
0.17
0.10
0.21
0.19
0.22
0.21
0.23
0.31
0.20
0.19
0.24
0.21
0.19
0.20
0.23
0.20
0.30
0.19
0.40
According to ICRP 80, the Effective Dose for adults is 0.064 mSv/MBq. Bladder wall
contributes to 47.6 % of the effective dose.
After ingestion of 11,100 MBq, the Effective Dose is about 710 mSv. The absorbed doses
are 322 mGy and 6,770 mGy for thyroid and bladder wall, respectively.
Incomplete blockage
Effective dose equivalent (mSv/MBq) at small uptake in the thyroid
uptake: 0.5 %
uptake: 1.0 %
uptake: 2.0 %
769844076
0.30
0.52
0.97
0.45
0.81
1.5
0.69
1.2
2.4
1.5
2.7
5.3
2.8
5.3
10
Page 14 of 17
Radiation exposure (Thyroid uptake: 15 %)
Organ
Adrenals
Bladder wall
Bone surfaces
Breast
GI-tract
Stomach wall
Small intest
ULI wall
LLI wall
Kidneys
Liver
Lungs
Ovaries
Pancreas
Red marrow
Spleen
Testes
Thyroid
Uterus
Other tissue
Effective dose equivalent
(mSv/MBq)
769844076
Absorbed dose per unit activity administered
(mGy/MBq)
Adult
15 years 10 years
5 years
1 year
0.036
0.043
0.071
0.11
0.22
0.52
0.64
0.98
1.5
2.9
0.047
0.067
0.094
0.14
0.24
0.043
0.043
0.081
0.13
0.25
0.46
0.28
0.059
0.042
0.060
0.032
0.053
0.043
0.052
0.054
0.042
0.028
210
0.054
0.065
6.6
0.58
0.35
0.065
0.053
0.075
0.041
0.071
0.059
0.062
0.074
0.051
0.035
340
0.068
0.089
10
0.84
0.62
0.10
0.082
0.11
0.068
0.12
0.092
0.10
0.099
0.081
0.058
510
0.11
0.14
15
1.5
1.0
0.16
0.13
0.17
0.11
0.19
0.14
0.15
0.14
0.12
0.094
1100
0.17
0.22
34
2.9
2.0
0.28
0.23
0.29
0.22
0.33
0.26
0.27
0.24
0.23
0.18
2000
0.31
0.40
62
Page 15 of 17
Radiation exposure (Thyroid uptake: 35 %)
Organ
Adrenals
Bladder wall
Bone surfaces
Breast
GI-tract
Stomach wall
Small intest
ULI wall
LLI wall
Kidneys
Liver
Lungs
Ovaries
Pancreas
Red marrow
Spleen
Testes
Thyroid
Uterus
Other tissue
Effective dose equivalent
(mSv/MBq)
Absorbed dose per unit activity administered
(mGy/MBq)
Adult
15 years 10 years
5 years
1 year
0.042
0.050
0.087
0.14
0.28
0.40
0.50
0.76
1.2
2.3
0.076
0.12
0.16
0.23
0.35
0.067
0.066
0.13
0.22
0.40
0.46
0.28
0.058
0.040
0.056
0.037
0.090
0.042
0.054
0.086
0.046
0.026
500
0.050
0.11
15
0.59
0.35
0.065
0.051
0.072
0.049
0.12
0.057
0.069
0.12
0.059
0.032
790
0.063
0.16
24
0.85
0.62
0.10
0.080
0.11
0.082
0.21
0.090
0.11
0.16
0.096
0.054
1200
0.10
0.26
36
1.5
1.0
0.17
0.13
0.17
0.14
0.33
0.14
0.18
0.22
0.15
0.089
2600
0.16
0.41
78
3.0
2.0
0.30
0.24
0.29
0.27
0.56
0.27
0.32
0.35
0.28
0.18
4700
0.30
0.71
140
According to ICRP 80, the Effective Dose for adults is 25.6 mSv/MBq.
After ingestion of 11,100 MBq, the Effective Dose is about 284 Sv. The absorbed doses
are 5,550 Gy and 4.5 Gy for thyroid and bladder wall, respectively.
769844076
Page 16 of 17
Radiation exposure (Thyroid uptake: 55 %)
Organ
Adrenals
Bladder wall
Bone surfaces
Breast
GI-tract
Stomach wall
Small intest
ULI wall
LLI wall
Kidneys
Liver
Lungs
Ovaries
Pancreas
Red marrow
Spleen
Testes
Thyroid
Uterus
Other tissue
Effective dose equivalent
(mSv/MBq)
12.
769844076
Absorbed dose per unit activity administered
(mGy/MBq)
Adult
15 years 10 years
5 years
1 year
0.049
0.058
0.11
0.17
0.34
0.29
0.36
0.54
0.85
1.6
0.11
0.17
0.22
0.32
0.48
0.091
0.089
0.19
0.31
0.56
0.46
0.28
0.058
0.039
0.051
0.043
0.13
0.041
0.058
0.12
0.051
0.026
790
0.046
0.16
24
0.59
0.35
0.067
0.049
0.068
0.058
0.18
0.056
0.076
0.18
0.068
0.031
1200
0.060
0.24
37
0.86
0.62
0.11
0.078
0.10
0.097
0.30
0.090
0.13
0.22
0.11
0.052
1900
0.099
0.37
56
1.5
1.0
0.18
0.13
0.17
0.17
0.48
0.15
0.21
0.29
0.17
0.087
4100
0.16
0.59
120
3.0
2.0
0.32
0.24
0.29
0.33
0.80
0.27
0.38
0.46
0.33
0.17
7400
0.30
1.0
220
INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
Not appropriate.
Page 17 of 17