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Active substance(s): SODIUM IODIDE I 131 SOLUTION / SODIUM IODIDE I 131 SOLUTION / SODIUM IODIDE I 131 SOLUTION

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
CAPSION
Sodium iodide [131I] capsule for therapy.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

The capsule contains as active substance sodium iodide [131I], with activities of 50 to
3700 MBq per capsule at calibration date.
[131I] iodine is produced by fission of [235U]uranium and by neutron bombardment of
stable tellurium in a nuclear reactor. [131I] iodine has a half-life of 8.04 days. It decays
by emission of gamma radiation of 365 keV (81 %), 637 keV (7.3 %) and 284 keV
(6.0 %) and beta radiation of 606 keV to stable [131Xe] xenon.
3.

PHARMACEUTICAL FORM

Capsule.
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

The activity administered is a matter for clinical judgement. The therapeutic effect is
only achieved after several months.
-

For the treatment of hyperthyroidism

The activity administered is usually in the range of 200 - 800 MBq but repeated
treatment may be necessary. The dose required depends on the diagnosis, the size of
the gland, thyroid uptake and iodine clearance. Patients should be rendered euthyroid
medically whenever possible before giving radioiodine treatment for hyperthyroidism.
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 1850 - 3700 MBq. It depends on the
remnant size and radioiodine uptake. In subsequent treatment for metastases,
administered activity is in the range 3700 - 11100 MBq.
The activity to be administered in children and adolescents should be a fraction of the
adult dose calculated from the body weight/surface area methods according to the
following equations :
Paediatric dose (MBq) = Error!
Paediatric dose (MBq) = Error!
Correction factors given for guidance are proposed below.
Fraction of adult dose :
3
kg
=
0.10
4
kg
=
0.14
6
kg
=
0.19
8
kg
=
0.23
10
kg
=
0.27
12
kg
=
0.32
14
kg
=
0.36
16
kg
=
0.40
18
kg
=
0.44
20
kg
=
0.46
(Paediatric Task Group, EANM)

22
0.50
24
0.53
26
0.56
28
0.58
30
0.62
32
0.65
34
0.68
36
0.71
38
0.73
40
0.76

kg

=

42 kg =

0.78

kg

=

44 kg =

0.80

kg

=

46 kg =

0.82

kg

=

48 kg =

0.85

kg

=

50 kg =

0.88

kg

=

=

kg

=

kg

=

kg

=

kg

=

52-54 kg
0.90
56-58 kg
0.92
60-62 kg
0.96
64-66 kg
0.98
68 kg =

=
=
=
0.99

The capsule is administered orally together with a drink. It should be swallowed
whole.
In patients with suspected gastrointestinal disease, great care should be taken when
administering [131I] capsules. The capsules should be swallowed whole with sufficient
fluid to ensure clear passage into the stomach and upper small intestine. Concomitant
use of H2 antagonists or proton pump inhibitors is advised.

After high doses used e.g. for the treatment of thyroid carcinoma, patients should be
encouraged to increase oral fluids to have frequent bladder emptying to reduce
bladder radiation.
4.3.

Contra-indications

Pregnancy.
For diagnostic purpose children under 10 years of age.
Thyroid scanning except in the follow-up of malignant disease or when [123I]
or [99mTc] are not available.
Patients with dysphagia, oesophageal stricture, active gastritis, gastric erosions
and peptic ulcer.
Patients with suspected reduced gastrointestinal motility.
4.4

Special warnings and precautions for use

This radiopharmaceutical may be received, used and administered only by authorised persons,
in designated clinical setting. Their receipt, storage, use, transfer and disposal are subject to
the regulations and/or appropriate licences of the local competent official organisation.
Radiopharmaceuticals should be prepared by the user in a manner which satisfies both
radiological and pharmaceutical quality requirements.
This preparation is likely to result in relatively a high radiation dose to most patients (see
section 4.8 and 5.4).
The administration of high dose radioiodine may result in significant environmental hazard.
These 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
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 3700 MBq [131I]. Another study has reported a small excess
leukaemia in patients receiving very high doses. A cumulative total activity higher than
26000 MBq is therefore not advisable.
The therapeutic administration of [131I] capsules in patients with significant renal impairment,
in which an activity adjustment is necessary, requires special attention.
To 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 compensate a potential transient impairment of male gonadal function by high radioiodine
therapeutic dose, sperm banking should be considered for men who have extensive disease.

A low iodine diet prior to therapy will enhance uptake into functioning thyroid tissue.
Thyroid replacement should be stopped prior to radioiodine administration for thyroid
carcinoma to ensure adequate uptake. A period of ten days is recommended for
triiodothyronine and six weeks for thyroxine. They should be restarted two weeks after
treatment. Similarly carbimazole and propylthiouracil should be stopped five days prior to
treatment of hyperthyroidism and restarted several days later.
In patients with a known hypersensitivity for gelatine or their metabolites, sodium iodide [131I]
solution should be preferred for the radioiodine therapy.

4.5.

Interaction with other medicinal products and other forms of interaction

Many pharmacological agents are known to interact with radioiodide. These may do
so 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].
For example antithyroid agents, carbimazole (or other imidazole derivatives such as
propylthiouracil), salicylates, steroids, sodium nitroprusside, sodium
sulfobromophthalein, perchlorate, miscellaneous agents (anticoagulants, antihistamines, antiparasitics, penicillins, sulphonamides, tolbutamide,
thiopentone), are normally withheld for 1 week ; phenylbutazone for 1-2 weeks,
expectorants, vitamins for 2 weeks ; natural or synthetic thyroid preparations (sodium
thyroxine, sodium liothyronine, thyroid extract) for 2-3 weeks ; amiodarone,
benzodiazepines, lithium for 4 weeks, topical iodides for 1-9 months ; and for
intravenous contrast agents, oral cholecystographic agents, iodine containing contrast
media for periods up to 1 year.
4.6.

Pregnancy and lactation

Sodium iodide [131I] is contraindicated during established or suspected pregnancy or
when pregnancy has not been excluded (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).
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. Alternative techniques which do not involve ionising radiation should be
considered. In the case of differentiated thyroid carcinoma diagnosed in pregnancy
therefore, radioiodine treatment should be postponed until after the pregnancy has
ended. Women receiving Sodium iodide [131I] should be advised NOT to become
pregnant within four months of administration.
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 the mother has ceased breast feeding and as to whether the
most appropriate choice of radiopharmaceutical has been made, bearing in mind the

secretion activity in breast milk. Breast feeding should be discontinued indefinitely
after Sodium iodide [131I] administration.
4.7.

Effects on ability to drive and use machines

No effects on the ability to drive or to operate machinery are to be expected after use
of the drug.
4.8

Undesirable effects

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.
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 radiation dose delivered (EDE) after therapeutic doses of Sodium iodide [131I] is
higher than 20 mSv.
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 adverse reactions of the allergic type following the administration of
sodium iodide [131I] have been reported (European system for reporting of adverse
reactions and drug defects). It is very probable that these reactions occur due to a
hypersensitivity against the gelatine of the capsules or their metabolites.
Early consequences
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 %).
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
antiinflammatory treatment but cases have occasionally been described of dosedependent 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.

Malfunction of the lachrymal glands, such as ocular dryness and nasolachrymal 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.
Transient impairment of male gonadal function may occur after high radioiodine
therapeutic dose or in the presence of pelvic metastasis.
In the treatment of metastasising 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. As a late consequence a single administration of over 5000 MBq or in
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.

4.9.

Overdose

This agent is intended for use by competent personnel within a hospital setting. As
such the risk of overdose is theoretical. The risks are related to the inadvertent
administration of excess radioactivity. High radiation exposure through overdose can
be reduced by means of administration of thyroid blocking agent, such as potassium
perchlorate, the use of the emetics and promoting a diuresis with frequent voiding of
urine.
5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic properties

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 beta
radiation which has a mean range of 0.5 mm.

5.2.

Pharmacokinetic properties

After oral administration sodium iodide [131I] is absorbed rapidly from the upper
gastrointestinal tract (90 % in 60 minutes). The pharmacokinetics follow 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 renally. 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. 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. 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 g/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.

5.4.

Radiation 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 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 "recycling" factor which takes into account the physiological status of the patient
(including iodine depletion) and the underlying pathology.

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
0.037
0.042
0.067
0.11
0.61
0.75
1.1
1.8
0.032
0.038
0.061
0.097
0.033
0.033
0.052
0.085

1 year
0.20
3.4
0.19
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

0.19
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
0.4

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

Bladder wall contributes to 50.8 % of the effective dose equivalent.

Incomplete blockage
Effective dose equivalent (mSv/MBq) at small uptake in the thyroid

uptake : 0.5 %
uptake : 1.0 %
uptake : 2.0 %

0.3
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

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)

Absorbed dose per unit activity administered
(mGy/MBq)
Adults
15 years 10 years 5 years
0.036
0.043
0.071
0.11
0.52
0.64
0.98
1.5
0.047
0.067
0.094
0.14
0.043
0.043
0.081
0.13

1 year
0.22
2.9
0.24
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

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

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

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
0.042
0.050
0.087
0.14
0.40
0.50
0.76
1.2
0.076
0.12
0.16
0.23
0.067
0.066
0.13
0.22

1 year
0.28
2.3
0.35
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

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

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

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)

Absorbed dose per unit activity administered
(mGy/MBq)
Adult
15 years 10 years 5 years
0.049
0.058
0.11
0.17
0.29
0.36
0.54
0.85
0.11
0.17
0.22
0.32
0.091
0.089
0.19
0.31

1 year
0.34
1.6
0.48
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

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

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

6.

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

PHARMACEUTICAL PARTICULARS

6.1.

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

List of excipients

Anhydrous sodium pyrophosphate
Sodium thiosulphate
Gelatine capsule
6.2.

Incompatibilities

None known
6.3.

Shelf life

21 days following manufacture.
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.
One capsule per vial.
6.6.

Instruction for use, handling and disposal

Capsules ready for use.
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.
The disposal of radioactive waste should be in accordance with relevant national and
international regulations.
7.

MARKETING AUTHORISATION HOLDER

CIS bio international
B.P. 32
91192 Gif-sur-Yvette Cedex
FRANCE
Tel. : +33-(0)1.69.85.70.70
Fax
: +33-(0)1.69.85.70.71
8.

MARKETING AUTHORISATION NUMBER

PL 11876/0015
9.
DATE OF FIRST AUTHORISATION/ RENEWAL OF
AUTHORISATION
5 October 2000

10

DATE OF REVISION OF THE TEXT
23/12/2008

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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