Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS

6.1   List of excipients
Capsule contents:
Disodium hydrogen phosphate dihydrate
Sodium thiosulphate
Sodium hydrogen carbonate
Sodium hydroxide
Sucrose
Sodium chloride
Water for injections
Capsule shell:
Gelatine

6.2   Incompatibilities
Not applicable.

6.3   Shelf life
Sodium iodide (I131) Capsules T expires 2 - 6 weeks after activity reference date and time.
Activity reference date and time and expiry date are printed on the label on the outer pack- age.

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
1 Capsule in a PETP single dose container.

6.6   Special precautions for disposal and other handling of the product The administration of radiopharmaceuticals creates risks for other persons from external ra- diation or contamination from spill of urine, vomiting etc. Radiation protection precautions in accordance with national regulations must therefore be taken.



When opening the container personnel should be aware that free radioactivity may be registered on monitors. This activity is due to Xe-131m which is formed for 1.17 % in the decay of I-131.
Though visible on monitors this does not pose a relevant risk for personnel.
The effective dose rate by inhalation of the Xe-131m formed is 0.1% of the dose rate at 1 m from a lead-shielded capsule.

Any unused product or waste material should be disposed of in accordance with local re- quirements.



7.    MANUFACTURED AND RELEASED BY
Mallinckrodt Medical B.V.
Westerduinweg 3
1755 LE Petten
The Netherlands

8.    MARKETING AUTHORISATION NUMBER(S)


9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION


10.   DATE OF REVISION OF THE TEXT
January 2011
11.   DOSIMETRY
Tabulated radiation dosimetry as reported in ICRP publication n°53 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 wall in addition to that due to gastric and salivary excretion. Assuming that the mean resi- dence time in the stomach is 0.5 hr, the absorbed dose to the stomach increases by about 30% for I-131.

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 “re-cycling” factor which takes into account the physiological sta- tus of the patient (including iodine depletion) and the underlying pathology.

The radiation exposure is mainly affecting the thyroid. The radiation exposure of the other organs is in the range of thousandths lower than that of the thyroid. It is dependant on the dietary intake of iodine (the uptake of radioactive iodine is in iodine deficient areas increased by up to 90 % and is decreased in iodine rich areas to 5 %). It is further dependant on the thyroid function (Eu-, hyper-, or hypothyroid) and on the presence of iodine accumulating tissues in the body. (E.g. the situation after excision of the thyroid, the presence of iodine accumulating metastases and on blockade of the thyroid.) The radiation exposure of all other organs is correspondingly higher or lower, depending on the degree of accumulation in the thyroid.



IODIDE
Thyroid blocked, uptake 0%

131
I 8.04 days
Absorbed dose per unit activity administered (mGy/MBq)
Organ                          Adult         15 years      10 years       5 years   1 year 
Adrenals                       3.7E-02       4.2E-02       6.7E-02        1.1E-01   2.0E-01 *Bladder wall                  6.1E-01       7.5E-01       1.1E+00        1.8E+00   3.4E+00 Bone surfaces                  3.2E-02       3.8E-02       6.1E-02        9.7E-02   1.9E-01 Breast                         3.3E-02       3.3E-02       5.2E-02        8.5E-02   1.7E-01 
GI-tract
Stomach wall                   3.4E-02       4.0E-02       6.4E-02        1.0E-01   1.9E-01 *Small intestine               3.8E-02       4.7E-02       7.5E-02        1.2E-01   2.2E-01 *ULI wall                      3.7E-02       4.5E-02       7.0E-02        1.2E-01   2.1E-01 *LLI wall                      4.3E-02       5.2E-02       8.2E-02        1.3E-01   2.3E-01 
*Kidneys                       6.5E-02       8.0E-02       1.2E-01        1.7E-01   3.1E-01 Liver                          3.3E-02       4.0E-02       6.5E-02        1.0E-01   2.0E-01 Lungs                          3.1E-02       3.8E-02       6.0E-02        9.6E-02   1.9E-01 Ovaries                        4.2E-02       5.4E-02       8.4E-02        1.3E-01   2.4E-01 Pancreas                       3.5E-02       4.3E-02       6.9E-02        1.1E-01   2.1E-01 
Red marrow                     3.5E-02       4.2E-02       6.5E-02        1.0E-01   1.9E-01 Spleen                         3.4E-02       4.0E-02       6.5E-02        1.0E-01   2.0E-01 Testes                         3.7E-02       4.5E-02       7.5E-02        1.2E-01   2.3E-01 Thyroid                        2.9E-02       3.8E-02       6.3E-02        1.0E-01   2.0E-01 Uterus                         5.4E-02       6.7E-02       1.1E-01        1.7E-01   3.0E-01 
Other tissue                   3.2E-02       3.9E-02       6.2E-02        1.0E-01   1.9E-01 
Effective dose equivalent 7.2E-02            8.8E-02       1.4E-01        2.1E-01   4.0E-01 (mSv/MBq)


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%:           3.0E-01        4.5E-01       6.9E-01        1.5E+00     2.8E+00 uptake 1%:             5.2E-01        8.1E-01       1.2E+00        2.7E+00     5.3E+00 uptake 2%:             9.7E-01        1.5E+00       2.4E+00        5.3E+00     1.0E+01 
Thyroid uptake 15%

Organ                   Adult         15 years      10 years      5 years      1 year 
Adrenals                3.6E-02       4.3E-02       7.1E-02       1.1E-01      2.2E-01 *Bladder wall           5.2E-01       6.4E-01       9.8E-01       1.5E+00      2.9E+00 Bone surfaces           4.7E-02       6.7E-02       9.4E-02       1.4E-01      2.4E-01 Breast                  4.3E-02       4.3E-02       8.1E-02       1.3E-01      2.5E-01 
GI-tract
Stomach wall            4.6E-01       5.8E-01       8.4E-01       1.5E+00      2.9E+00 *Small intestine        2.8E-01       3.5E-01       6.2E-01       1.0E+00      2.0E+00 *ULI wall               5.9E-02       6.5E-02       1.0E-01       1.6E-01      2.8E-01 *LLI wall               4.2E-02       5.3E-02       8.2E-02       1.3E-01      2.3E-01 
*Kidneys                6.0E-02       7.5E-02       1.1E-01       1.7E-01      2.9E-01 Liver                   3.2E-02       4.1E-02       6.8E-02       1.1E-01      2.2E-01 Lungs                   5.3E-02       7.1E-02       1.2E-01       1.9E-01      3.3E-01 Ovaries                 4.3E-02       5.9E-02       9.2E-02       1.4E-01      2.6E-01 Pancreas                5.2E-02       6.2E-02       1.0E-01       1.5E-01      2.7E-01 
Red marrow              5.4E-02       7.4E-02       9.9E-02       1.4E-01      2.4E-01 Spleen                  4.2E-02       5.1E-02       8.1E-02       1.2E-01      2.3E-01 Testes                  2.8E-02       3.5E-02       5.8E-02       9.4E-02      1.8E-01 Thyroid                 2.1E+02       3.4E+02       5.1E+02       1.1E+03      2.0E+03 Uterus                  5.4E-02       6.8E-02       1.1E-01       1.7E-01      3.1E-01 
Other tissue            6.5E-02       8.9E-02       1.4E-01       2.2E-01      4.0E-01 
Effective dose       6.6E+00          1.0E+01       1.5E+01       3.4E+01      6.2E+01 equivalent (mSv/MBq)



Thyroid uptake 35%


Organ                  Adult     15 years   10 years   5 years   1 year 
Adrenals               4.2E-02   5.0E-02    8.7E-02    1.4E-01   2.8E-01 *Bladder wall          4.0E-01   5.0E-01    7.6E-01    1.2E+00   2.3E+00 Bone surfaces          7.6E-02   1.2E-01    1.6E-01    2.3E-01   3.5E-01 Breast                 6.7E-02   6.6E-02    1.3E-01    2.2E-01   4.0E-01 
GI-tract
Stomach wall           4.6E-01   5.9E-01    8.5E-01    1.5E+00   3.0E+00 *Small intestine       2.8E-01   3.5E-01    6.2E-01    1.0E+00   2.0E+00 *ULI wall              5.8E-02   6.5E-02    1.0E-01    1.7E-01   3.0E-01 *LLI wall              4.0E-02   5.1E-02    8.0E-02    1.3E-01   2.4E-01 
*Kidneys               5.6E-02   7.2E-02    1.1E-01    1.7E-01   2.9E-01 Liver                  3.7E-02   4.9E-02    8.2E-02    1.4E-01   2.7E-01 Lungs                  9.0E-02   1.2E-01    2.1E-01    3.3E-01   5.6E-01 Ovaries                4.2E-02   5.7E-02    9.0E-02    1.4E-01   2.7E-01 Pancreas               5.4E-02   6.9E-02    1.1E-01    1.8E-01   3.2E-01 
Red marrow             8.6E-02   1.2E-01    1.6E-01    2.2E-01   3.5E-01 Spleen                 4.6E-02   5.9E-02    9.6E-02    1.5E-01   2.8E-01 Testes                 2.6E-02   3.2E-02    5.4E-02    8.9E-02   1.8E-01 Thyroid                5.0E+02   7.9E+02    1.2E+03    2.6E+03   4.7E+03 Uterus                 5.0E-02   6.3E-02    1.0E-01    1.6E-01   3.0E-01 
Other tissue           1.1E-01   1.6E-01    2.6E-01    4.1E-01   7.1E-01 
Effective dose       1.5E+01     2.4E+01    3.6E+01    7.8E+01   1.4E+02 equivalent (mSv/MBq)



Thyroid uptake 55%

Organ                    Adult          15 years       10 years       5 years       1 year 
Adrenals                 4.9E-02        5.8E-02        1.1E-01        1.7E-01       3.4E-01 *Bladder wall            2.9E-01        3.6E-01        5.4E-01        8.5E-01       1.6E+00 Bone surfaces            1.1E-01        1.7E-01        2.2E-01        3.2E-01       4.8E-01 Breast                   9.1E-02        8.9E-02        1.9E-01        3.1E-01       5.6E-01 
GI-tract
Stomach wall             4.6E-01        5.9E-01        8.6E-01        1.5E+00       3.0E+00 *Small intestine         2.8E-01        3.5E-01        6.2E-01        1.0E+00       2.0E+00 *ULI wall                5.8E-02        6.7E-02        1.1E-01        1.8E-01       3.2E-01 *LLI wall                3.9E-02        4.9E-02        7.8E-02        1.3E-01       2.4E-01 
*Kidneys                 5.1E-02        6.8E-02        1.0E-01        1.7E-01       2.9E-01 Liver                    4.3E-02        5.8E-02        9.7E-02        1.7E-01       3.3E-01 Lungs                    1.3E-01        1.8E-01        3.0E-01        4.8E-01       8.0E-01 Ovaries                  4.1E-02        5.6E-02        9.0E-02        1.5E-01       2.7E-01 Pancreas                 5.8E-02        7.6E-02        1.3E-01        2.1E-01       3.8E-01 
Red marrow               1.2E-01        1.8E-01        2.2E-01        2.9E-01       4.6E-01 Spleen                   5.1E-02        6.8E-02        1.1E-01        1.7E-01       3.3E-01 Testes                   2.6E-02        3.1E-02        5.2E-02        8.7E-02       1.7E-01 Thyroid                  7.9E+02        1.2E+03        1.9E+03        4.1E+03       7.4E+03 Uterus                   4.6E-02        6.0E-02        9.9E-02        1.6E-01       3.0E-01 
Other tissue             1.6E-01        2.4E-01        3.7E-01        5.9E-01       1.0E+00 
Effective dose       2.4E+01            3.7E+01        5.6E+01        1.2E+02       2.2E+02 equivalent (mSv/MBq)


12.      INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
The capsules are ready to use.

For the recommendation how to measure the activity see section 4.2, paragraph administration pro- tocol.

Any unused product or waste material should be disposed of in accordance with local requirements.