Oral Sodium Iodide 131 I Solution
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
I-131-S-1.
Sodium iodide (131I) CIS bio international 1110 MBq/mL oral solution.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 2 mg lacidipine.
Excipient with known effect:
Each film-coated tablet contains 124.25 mg lactose monohydrate.
For the full list of excipients, see section 6.1.
Each mL contains 1110 MBq of sodium iodide (131I) at calibration date.
The total activity per vial ranges from 1 110 MBq to 11 100 MBq at calibration date.
Iodine-131 is produced by fission of uranium-235 or neutron bombardment of stable tellurium in a nuclear reactor. It decays by emission of gamma radiations of 365 Kev (81%), 637 Kev (7.3%) and 284 Kev (6.1%) and beta radiations of maximal energy of 606 Kev to stable Xenon-131. Iodine-131 has a half life of 8.04 days.
Excipient with known effect:
Each mL contains 1.8 mg of sodium.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Oral solution.
Clear, colourless solution with a pH between 7.0 and 10.0
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Diagnostic indications
- In the management of thyroid carcinoma, sodium iodide is used to identify thyroid remnant and metastases (after ablation).
For diagnostic use, sodium iodide (131I) is indicated in adults. In children over 10 years old it is indicated when radiopharmaceuticals with more favourable dosimetry, eg Iodide-123 or Technetium-99m, are not available.
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 (131-I) therapy is often combined with surgical intervention and with antithyroid medications.
4.2 Posology and method of administration
Posology Diagnostic use
The maximum recommended activity for an adult patient (70 kg) for metastases and thyroid remnant post thyroid ablation is 400 MBq.
Therapeutic use
The activity administered is a matter for clinical judgement. The therapeutic effect is only achieved after several weeks.
- For the treatment of hyperthyroidism
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.
The following target organ doses may be used for posology calculation:
• autonomous nodule 300 - 400 Gy absorbed dose to target organ
• toxic multinodular goitre 150 - 200 Gy absorbed dose to target organ
• Graves’ disease 200 Gy absorbed dose to target organ
In Graves’ disease, multifocal or disseminated autonomy, the above mentioned target organ doses are related to the overall weight of the thyroid gland, however in the unifocal autonomy, the target organ dose is only related to the weight of the adenoma.
The activity to be administered may be calculated according to the following equation:
A (MBq)
Target dose (Gy) x target volume (ml) max. uptake 131I (%) x effective T (days)
x K
Legend:
target dose target volume
max. uptake I-131
effective T
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) max. uptake of I-131 in the thyroid gland or nodules in % of the administered activity as established in a test dose effective half life of I-131 in the thyroid gland
K 24.67
Other dosimetric procedures may also be used including sodium pertechnetate (99mTc) thyroid uptake tests to determine the appropriate target organ dose (Gy).
Fixed dose protocols may also be used.
The range of activities usually 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.
- For thyroid ablation and treatment of metastases
The administered activities following total or sub total 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.
Renal impairment
Careful consideration of the activity to be administered is required since an increased radiation exposure is possible in these patients.
An adjustement of the posology should be considered.
Paediatric population
For therapeutic use 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 Multidose vial.
For patient preparation, see section 4.4.
Oral solution of sodium iodide (131I) is administered orally by instructing the patients to drink the liquid through a straw (see section 6.6).
Acquisition of images
Images should be obtained at 18 - 24 hours after ingestion.
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).
- For diagnostic purpose in children under 10 years of age.
- Patients with dysphagia, oesophageal stricture, 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 diagnostic information or 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) in patients with significant renal impairment, in which an activity adjustment is necessary, requires special attention.
Paediatric population
For information on the use in paediatric population, see section 4.2.
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 antithyroid medicinal products or when serious adverse reactions to antithyroid medicinal products do occur.
Patient preparation
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.
A low iodine diet prior to therapy will enhance uptake into functioning thyroid tissue. Sperm banking should be considered for men who have extensive disease (see section 4.6.).
Breast-feeding women must be advised to discontinue breast-feeding 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 ( I). Concomitant use of H2 antagonists or proton pump inhibitors is advised in order to address the possible gastrointestinal reactions.
The treatment of Graves’ disease by radioactive iodine should be associated to concomitant medication by corticosteroids in patients with Graves’ ophthalmopathy.
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 treatment
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, it is recommended to avoid close contact between treated patients and infants and pregnant women. The period of close contact restriction should be adapted to the administered activity and the type of pathology.
Specific warnings
There is no evidence of an increased incidence of malignancies (cancer, leukemia or mutations) in man with patients treated for diagnostic purpose with Sodium Iodide I-131.
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 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 greater than 3,700 MBq 131-I. Another
study has reported a small excess leukemia in patients receiving very high doses. A cumulative total activity higher than 26000 MBq is therefore not advisable.
This medicinal product contains 1.8 mg of sodium per ml, which is less than 1 mmol (23 mg) per dose administered at calibration date, i.e. is essentially “sodium free”.
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. 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 I-131.
For example, the treatment with the following substances should be discontinued:
|
Active substances |
Period of withhold before administration of 131-iodine |
|
Antithyroid agents (e.g. carbimazole, or other imidazole derivatives such as propylthiouracil) and perchlorate |
1 week before starting treatment till several days after |
|
Salicylates, steroids, sodium nitroprusside, sodium sulfobromophthalein, anticoagulants, antihistamines, antiparasitics, penicillins, sulphonamides, tolbutamide, thiopentone |
1 week |
|
Phenylbutazone |
1-2 week(s) |
|
Containing iodine expectorants and vitamins |
Approx. 2 weeks |
|
Thyroid hormone preparations |
Triiodothyronine 2 weeks Thyroxine 5 weeks |
|
Amiodarone *, benzodiazepines, lithium |
Approx. 4 weeks |
|
Containing iodine preparations for topical use |
1-9 months |
|
Containing iodine contrast media |
Up to 1 year |
*Due to the long half-life of amiodarone, iodine uptake in the thyroid tissue can be decreased for several months.
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 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 ( I) 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 the foetal thyroid gland avidly concentrates iodine during the second and third trimesters).
Should differentiated thyroid carcinoma be diagnosed during pregnancy, radioactive iodine treatment must be postponed until after the pregnancy.
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 breast-feeding, 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, breast-feeding must be discontinued for 68 weeks before radioiodine administration in order to ensure that lactation-associated increase in breast sodium iodide symporter activity has returned to normal. Breast-feeding must not be resumed after sodium iodide-131.therapy. Breast-feeding can be safely undertaken after future pregnancy.
Close contact
For radioprotection reasons, it is recommended to avoid close contact with infants and pregnant women. 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 (131I) 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:
|
MedDRA Body system SOCs |
Preferred term |
Frequency |
|
Neoplasms benign, malignant and unspecified (incl.cysts and polyps) |
Gastric cancer |
Not known |
|
Bladder cancer | ||
|
Leukaemia | ||
|
Breast cancer | ||
|
Cancer induction | ||
|
Blood and lymphatic system disorders |
Bone Marrow Failure |
Not known |
|
Thrombocytopenia | ||
|
Erythrocytopenia | ||
|
Leukocytosis |
Common | |
|
Immune system disorders |
Hypersensitivity |
Not known |
|
Endocrine disorders |
Basedow’s disease |
Common |
|
Hyperthyroidism |
Not known | |
|
Hypothyroidism |
Very common | |
|
Hypoparathyroidism |
Uncommon | |
|
Thyroiditis |
Very common | |
|
Thyrotoxic crisis |
Not known | |
|
Endocrine ophthalmopathy |
Common | |
|
Nervous system disorders |
Brain oedema |
Not known |
|
Eye disorders |
Dry eye |
Very common |
|
Dacryostenosis acquired | ||
|
Lacrimal disorders | ||
|
Eye disorders |
Uncommon | |
|
Respiratory, thoracic and mediastinal disorders |
Pulmonary fibrosis, pneumonia, respiratory distress |
Not known |
|
Dyspnoea | ||
|
Tracheal stenosis | ||
|
Tracheitis | ||
|
Gastrointestinal disorders |
Salivary gland enlargment |
Very common |
|
Salivary gland pain | ||
|
Sialoadenitis | ||
|
Vomiting | ||
|
Nausea | ||
|
Tooth loss |
Not known | |
|
Gastrointestinal disorders |
Very common | |
|
Ageusia, dysgeusia | ||
|
Dry mouth | ||
|
Reproductive system and breast disorders |
Infertility male, infertility female, azoospermia, menstrual disorder, ovarian failure |
Not known |
|
Congenital, familial and genetic disorders |
Hereditary defects |
Not known |
|
Congenital hypothyroidism | ||
|
General disorders and administration site conditions |
Localised oedema |
Not known |
|
Discomfort | ||
|
Pain | ||
|
Fatigue |
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)
- Early consequences
Some cases of adverse reactions have been reported following the administration of sodium iodide I-131, 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).
Therapeutic quantities of I-131 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 trachaeal 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 (131I) may lead to exacerbation of an already existing hyperthyroidism after 2 - 10 days or even to thyrotoxic crisis.
Malfunction of the lachrymal glands, such as ocular dryness and nasolachrimal 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.
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 erytrocytopenia, which may be fatal. Transient leucocytosis is frequently observed.
Epidemiological studies report a higher incidence of stomach cancer in patients receiving I-131.
After higher activities, typically those used in the treatment of thyroid malignancies, an increased incidence of leukemia 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. As the effective dose equivalent is 28.8 mSv when the maximal recommended activity of 400 MBq is administered for diagnostic dose, these adverse reactions are expected to occur with a low probability. The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer (leukemia, gastric, bladder or breast cancers) 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 equivalent is 799 mSv when the maximal recommended activity of 11,100 MBq is administered.
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 the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard.
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. To reduce the uptake of iodide-131, emetics can be given.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group:
Diagnostic Radiopharmaceuticals, ATC code: V09FX03. Therapeutic Radiopharmaceuticals, 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.
The P irradiation will dose-dependently decrease cell function and cell division leading to cell destruction.
Pharmacodynamic effects
Iodide in the amount used for diagnostic and 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
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 I-131 sodium iodide approximately 40% of the activity has an effective half life of 0.4 days and the remaining 60%, 8 days.
Elimination
Urinary excretion is 37-75%, faecal excretion is about 10% with almost negligible excretion in sweat.
5.3 Preclinical safety data
Because of the small quantities of substance administered compared with the normal food intake of iodine (40-500 mcg/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
Sodium carbonate
Sodium bicarbonate
Sodium thiosulfate
Sodium hydroxide (pH adjustement)
Water for injections
6.2 Incompatibilities
Not appropriate.
6.3 Shelf life 29 days from the day of 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 of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.
6.5 Nature and contents of container
15 mL colourless, European Pharmacopoeia type I, drawn glass vial, closed with a grey rubber stopper and an aluminium capsule.
Pack size: One multidose vial containing 1 110 MBq (1 ml) to 11 100 MBq (10 ml) at calibration date.
6.6 Special precautions for disposal
General warnings
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.
Solution ready to use.
Usual precautions regarding sterility and radioprotection should be respected.
Before use, packaging, pH, radioactivity and gamma spectrum will be checked.
If at any time in the preparation of this product the integrity of this vial is compromised it should not be used.
The vial should never be opened and must be kept inside its lead shielding.
After disinfection of the stopper, perforate it with a needle fitted with an air intake connected to a single use tubing. The solution is then sucked up by the patient through the tubing. The volume corresponding to the calculated activity can also be withdrawn from the vial to be administered orally by instructing the patients to drink the liquid through a straw.
Solutions of sodium iodide (131I) should be handled strictly under a ventilated hood and the personnel handling these solutions should be given a urinary radiotoxicologic control examination.
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 a high dose of 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.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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(S)
PL 11876/0014
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 19 September 1997 Date of latest renewal: 12 June 2006
10 DATE OF REVISION OF THE TEXT
27/11/2015
11 DOSIMETRY
Tabulated radiation dosimetry as reported in ICRP publication n°53 (1987) are reported.
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 in addition to that due to gastric and salivary excretion. Assuming that the mean residence time in the stomach is 0.5 hr, the absorbed dose to the stomach increases by about 30% for I-131.
For diagnostic use
The Effective Dose Equivalent resulting from an administration activity of 400 MBq is typically between 28.8 (0% thyroid uptake) and 9,600 mSv (55% thyroid uptake).
Under similar circumstances, the dose to the thyroid will vary from 11.6 to 316,000 mGy and the dose to the bladder wall from 244 mGy to 116 mGy.
The figures quoted are on the basis of:
Thyroid mass : 20 g
Biological half-life : 80 days
Recycling factor : 1.8
For therapeutic use
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 radiation 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.
IODIDE
Thyroid blocked, uptake 0%
_8.04 days
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) | ||||
|
Adult |
15 years |
10 years |
5 years |
1 year | |
|
Adrenals |
0.037 |
0.042 |
0.067 |
0.11 |
0.20 |
|
Bladder wall |
0.61 |
0.75 |
1.1 |
1.8 |
3.4 |
|
Bone surfaces |
0.032 |
0.038 |
0.061 |
0.097 |
0.19 |
|
Breast |
0.033 |
0.033 |
0.052 |
0.085 |
0.17 |
|
GI-tract | |||||
|
Stomach wall |
0.034 |
0.040 |
0.064 |
0.10 |
0.19 |
|
Small intest |
0.038 |
0.047 |
0.075 |
0.12 |
0.22 |
|
ULI wall |
0.037 |
0.045 |
0.070 |
0.12 |
0.21 |
|
LLI wall |
0.043 |
0.052 |
0.082 |
0.13 |
0.23 |
|
Kidneys |
0.065 |
0.080 |
0.12 |
0.17 |
0.31 |
|
Liver |
0.033 |
0.040 |
0.065 |
0.10 |
0.20 |
|
Lungs |
0.031 |
0.038 |
0.060 |
0.096 |
0.19 |
|
Ovaries |
0.042 |
0.054 |
0.084 |
0.13 |
0.24 |
|
Pancreas |
0.035 |
0.043 |
0.069 |
0.11 |
0.21 |
|
Red marrow |
0.035 |
0.042 |
0.065 |
0.10 |
0.19 |
|
Spleen |
0.034 |
0.040 |
0.065 |
0.10 |
0.20 |
|
Testes |
0.037 |
0.045 |
0.075 |
0.12 |
0.23 |
|
Thyroid |
0.029 |
0.038 |
0.063 |
0.10 |
0.20 |
|
Uterus |
0.054 |
0.067 |
0.11 |
0.17 |
0.30 |
|
Other tissue |
0.032 |
0.039 |
0.062 |
0.10 |
0.19 |
|
Effective dose equivalent (mSv/MBq) |
0.072 |
0.088 |
0.14 |
0.21 |
0.4 |
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 % |
0.3 |
0.45 |
0.69 |
1.5 |
2.8 |
|
uptake: 1.0 % |
0.52 |
0.81 |
1.2 |
2.7 |
5.3 |
|
uptake: 2.0 % |
0.97 |
1.5 |
2.4 |
5.3 |
10 |
|
Absorbed dose per unit activity administered (mGy/MBq) | |||||
|
Organ |
Adults |
15 years |
10 years |
5 years |
1 year |
|
Adrenals |
0.036 |
0.043 |
0.071 |
0.11 |
0.22 |
|
Bladder wall |
0.52 |
0.64 |
0.98 |
1.5 |
2.9 |
|
Bone surfaces |
0.047 |
0.067 |
0.094 |
0.14 |
0.24 |
|
Breast |
0.043 |
0.043 |
0.081 |
0.13 |
0.25 |
|
Gl-tract | |||||
|
Stomach wall |
0.46 |
0.58 |
0.84 |
1.5 |
2.9 |
|
Small intest |
0.28 |
0.35 |
0.62 |
1.0 |
2.0 |
|
ULI wall |
0.059 |
0.065 |
0.10 |
0.16 |
0.28 |
|
LLI wall |
0.042 |
0.053 |
0.082 |
0.13 |
0.23 |
|
Kidneys |
0.060 |
0.075 |
0.11 |
0.17 |
0.29 |
|
Liver |
0.032 |
0.041 |
0.068 |
0.11 |
0.22 |
|
Lungs |
0.053 |
0.071 |
0.12 |
0.19 |
0.33 |
|
Ovaries |
0.043 |
0.059 |
0.092 |
0.14 |
0.26 |
|
Pancreas |
0.052 |
0.062 |
0.10 |
0.15 |
0.27 |
|
Red marrow |
0.054 |
0.074 |
0.099 |
0.14 |
0.24 |
|
Spleen |
0.042 |
0.051 |
0.081 |
0.12 |
0.23 |
|
Testes |
0.028 |
0.035 |
0.058 |
0.094 |
0.18 |
|
Thyroid |
210 |
340 |
510 |
1100 |
2000 |
|
Uterus |
0.054 |
0.068 |
0.11 |
0.17 |
0.31 |
|
Other tissue |
0.065 |
0.089 |
0.14 |
0.22 |
0.40 |
|
Effective dose equivalent (mSv/MBq) |
6.6 |
10 |
15 |
34 |
62 |
|
Organ |
Absorbed dose per unit activity administered (mGy/MBq) | ||||
|
Adult |
15 years |
10 years |
5 years |
1 year | |
|
Adrenals |
0.042 |
0.050 |
0.087 |
0.14 |
0.28 |
|
Bladder wall |
0.40 |
0.50 |
0.76 |
1.2 |
2.3 |
|
Bone surfaces |
0.076 |
0.12 |
0.16 |
0.23 |
0.35 |
|
Breast |
0.067 |
0.066 |
0.13 |
0.22 |
0.40 |
|
Gl-tract | |||||
|
Stomach wall |
0.46 |
0.59 |
0.85 |
1.5 |
3.0 |
|
Small intest |
0.28 |
0.35 |
0.62 |
1.0 |
2.0 |
|
ULI wall |
0.058 |
0.065 |
0.10 |
0.17 |
0.30 |
|
LLI wall |
0.040 |
0.051 |
0.080 |
0.13 |
0.24 |
|
Kidneys |
0.056 |
0.072 |
0.11 |
0.17 |
0.29 |
|
Liver |
0.037 |
0.049 |
0.082 |
0.14 |
0.27 |
|
Lungs |
0.090 |
0.12 |
0.21 |
0.33 |
0.56 |
|
Ovaries |
0.042 |
0.057 |
0.090 |
0.14 |
0.27 |
|
Pancreas |
0.054 |
0.069 |
0.11 |
0.18 |
0.32 |
|
Red marrow |
0.086 |
0.12 |
0.16 |
0.22 |
0.35 |
|
Spleen |
0.046 |
0.059 |
0.096 |
0.15 |
0.28 |
|
Testes |
0.026 |
0.032 |
0.054 |
0.089 |
0.18 |
|
Thyroid |
500 |
790 |
1200 |
2600 |
4700 |
|
Uterus |
0.050 |
0.063 |
0.10 |
0.16 |
0.30 |
|
Other tissue |
0.11 |
0.16 |
0.26 |
0.41 |
0.71 |
|
Effective dose equivalent (mSv/MBq) |
15 |
24 |
36 |
78 |
140 |
|
Absorbed dose per unit activity administered (mGy/MBq) | |||||
|
Organ |
Adult |
15 years |
10 years |
5 years |
1 year |
|
Adrenals |
0.049 |
0.058 |
0.11 |
0.17 |
0.34 |
|
Bladder wall |
0.29 |
0.36 |
0.54 |
0.85 |
1.6 |
|
Bone surfaces |
0.11 |
0.17 |
0.22 |
0.32 |
0.48 |
|
Breast |
0.091 |
0.089 |
0.19 |
0.31 |
0.56 |
|
GI-tract | |||||
|
Stomach wall |
0.46 |
0.59 |
0.86 |
1.5 |
3.0 |
|
Small intest |
0.28 |
0.35 |
0.62 |
1.0 |
2.0 |
|
ULI wall |
0.058 |
0.067 |
0.11 |
0.18 |
0.32 |
|
LLI wall |
0.039 |
0.049 |
0.078 |
0.13 |
0.24 |
|
Kidneys |
0.051 |
0.068 |
0.10 |
0.17 |
0.29 |
|
Liver |
0.043 |
0.058 |
0.097 |
0.17 |
0.33 |
|
Lungs |
0.13 |
0.18 |
0.30 |
0.48 |
0.80 |
|
Ovaries |
0.041 |
0.056 |
0.090 |
0.15 |
0.27 |
|
Pancreas |
0.058 |
0.076 |
0.13 |
0.21 |
0.38 |
|
Red marrow |
0.12 |
0.18 |
0.22 |
0.29 |
0.46 |
|
Spleen |
0.051 |
0.068 |
0.11 |
0.17 |
0.33 |
|
Testes |
0.026 |
0.031 |
0.052 |
0.087 |
0.17 |
|
Thyroid |
790 |
1200 |
1900 |
4100 |
7400 |
|
Uterus |
0.046 |
0.060 |
0.099 |
0.16 |
0.30 |
|
Other tissue |
0.16 |
0.24 |
0.37 |
0.59 |
1.0 |
|
Effective dose equivalent (mSv/MBq) |
24 |
37 |
56 |
120 |
220 |
Detailed information on this medicinal product is available on the website of the MHRA.
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
No data held.