tic thyroid hormones triiodothyronine thyroxine 2 weeks 4 weeks iodide-containing foods: iodized salt, dairy products, egg yolks, seafood, turkey and liver 2 weeks kelp, agar, carrageenan, lugol solution 3 weeks saturated solution of potassium iodide 3 weeks topical iodide (e.g., surgical skin preparation) 3 weeks intravenous radiographic contrast agents water soluble lipophilic 2 months 6 months amiodarone 6 months many drugs and iodine-containing foods interfere with the accumulation of radioiodide by the thyroid. instruct patients to maintain a low-iodide diet (2 weeks) and discontinue anti-thyroid therapy (3 days) before administration. ( 5.8 , 7 )

ys before administration of sodium iodide i 131 [see drug interactions (7) ] . consider a beta-blocker pre or post-treatment to minimize the risk of hyperthyroidism and thyroid storm. the thyroiditis may cause gland enlargement resulting in tenderness and swelling of the neck, pain on swallowing, sore throat, and cough; which may occur approximately the third day after sodium iodide i 131 administration. consider management with pain-reliever or anti-inflammatory medications. 5.2 radiation-induced toxicities sodium iodide i 131 may cause radiation induced toxicities [see adverse reactions (6) ] : dose-dependent fatalities (bone marrow suppression, malignancy). dose-dependent hematopoietic suppression which manifests as a transient thrombocytopenia or neutropenia 3-5 weeks following sodium iodide i 131 administrations, may lead to increased susceptibility to infections or bleeding. salivary gland toxicity: sialadenitis, xerostomia. lacrimal gland toxicity: conjunctivitis, xerophthalmia, and epiphora. increased risk of developing new solid tumors and leukemias. obtain a complete blood count within one month of therapy. if patients show leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide i 131 activity, while delivering less than 2 gy to the bone marrow. advise good hydration for one week following sodium iodide i 131 administration and stimulate salivary flow via a sialagogue (e.g. sugar-free candy or gum, pilocarpine, and ascorbic acid) to reduce radiation exposure to the salivary glands. advise patients to void frequently after administration of radioiodide to enhance excretion. 5.3 hypersensitivity reactions hypersensitivity reactions including anaphylaxis may occur in patients who receive sodium iodide i 131. although iodide is not considered an allergen, hypersensitivity reactions may occur in relation with excipients or chemical component of the capsule, such as sodium thiosulfate. obtain and document an allergy history, particularly a sulfite allergy. emergency resuscitation equipment and personnel should be immediately available [see adverse reactions (6) ] . 5.4 embryo-fetal toxicity sodium iodide i-131 solution is contraindicated in pregnancy because sodium iodide i-131 crosses the placenta and fetal exposure can lead to neonatal hypothyroidism. multiple reports in the published literature describe hypothyroidism in the neonates following in utero exposure to sodium iodide i-131. some cases of neonatal hypothyroidism were severe and irreversible. verify pregnancy status of females of reproductive potential prior to initiating sodium iodide i-131 solution treatment. advise females and males of reproductive potential to use effective contraception during treatment with sodium iodide i-131 solution and for at least six months after the last dose [see use in specific populations (8.1 , 8.3) ]. 5.5 increased radiation exposure to breast tissue with lactation sodium iodide i-131 solution is contraindicated in lactating women because sodium iodide i-131 concentrates in the breast via the increased expression of the sodium iodide symporter in breast tissue with lactation. the literature describes moderate to marked radioiodine uptake in the breast tissue for 5 to 32 weeks post cessation of breast feeding. advise lactating women to discontinue breast feeding at least 6 weeks prior to administration of sodium iodide i-131 to allow sufficient time for involution to occur and to avoid excess concentration of sodium iodide i-131 in breast tissue. consider administration of drugs to suppress lactation. consider diagnostic scintigraphy before administration of sodium iodide i-131 to assess the persistence of uptake by breast tissue. if sodium iodide i-131 is administered in the postpartum period, the lactating mother should not breastfeed the infant [see use in specific populations (8.2) ] . 5.6 transient infertility transient dose-related impairment of testicular function in men and transient ovarian insufficiency in women has been reported after sodium iodide i-131 therapy. sperm banking for men may be considered prior to administration of sodium iodide i-131 solution for thyroid carcinoma [see use in specific populations (8.3) ] . 5.7 risk of radiation exposure household contacts instruct patients to follow radiation safety precautions after receiving sodium iodide i-131 to minimize the radiation contamination of other persons or the environment. patients should avoid close contact with others, especially pregnant women and children, and take care to avoid contamination of other persons or the environment with body fluids. patients and healthcare providers sodium iodide i-131 contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. follow safe handling and administration to minimize radiation exposure to the patient and healthcare providers. 5.8 risk of decreased effectiveness of therapy certain food or drugs may alter the thyroid uptake of sodium iodide i 131 and diminish its effectiveness. recent intake of stable iodide in any form, or the use of thyroid or anti-thyroid drugs may diminish thyroid uptake of sodium iodide i 131 [see drug interactions (7) ] .

the appropriate governmental agency authorized to license the use of radiopharmaceuticals. use waterproof gloves when handling and administering the product. maintain adequate shielding during the life of the product. measure patient dose with a suitable radioactivity calibration system immediately prior to administration. 2.2 important administration instructions do not directly administer the concentrated sodium iodide i-131 solution provided to patients. the concentrated sodium iodide i 131 solution must be diluted and prepared prior to administration [see dosage and administration (2.4) ] . obtain a pregnancy test in females of reproductive potential prior to administration to verify the absence of pregnancy [see contraindications (4) and use in specific populations (8.1, 8.3 )] . instruct patients to fast at least 2 hours before and 2 hours after administration to ensure absorption. instruct patients to hydrate before and after administration of sodium iodide i-131 and to void frequently to enhance urinary elimination of the radioiodide that is not absorbed by the thyroid gland [see warnings and precautions (5.2) ] . instruct patients to maintain a low-iodide diet two weeks prior to radioiodide administration and continue for several days during the uptake or imaging process [see warnings and precautions (5.8) and drug interactions (7) ] . instruct patients to discontinue the anti-thyroid therapy three days before administration of sodium iodide i 131 [see warnings and precautions (5.8) and drug interactions (7) ] . for patients with a history of renal impairment, evaluate renal function for therapeutic planning and consider dosimetry [see use in specific populations (8.6) ] . obtain a complete blood count within one month of therapy. if patients show leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide i 131 activity, while delivering less than 2 gy to the bone marrow [see warnings and precautions (5.2) ] . 2.3 recommended dosage and administration individualization of therapy the recommended dose for orally administered sodium iodide i 131 capsules or solution is based on the thyroid gland uptake as well as the size of the gland. thyroidal uptake and size should be determined by the physician prior to treatment and may be useful in calculating the therapeutic dose to be administered to the individual patient. treatment of hyperthyroidism the recommended dose is 148 to 370 mbq (4 to 10 mci) administered orally. toxic nodular goiter may require a larger dose. treatment of thyroid carcinoma the recommended dose is 1100 to 3700 mbq (30 to 100 mci) administered orally. for subsequent ablation of metastases, the recommended dose is 3700 to 7400 mbq (100 to 200 mci) administered orally. 2.4 dilution and preparation instructions drug handling wear waterproof gloves throughout the entire handling and administration procedure. make all transfers of radioactive solutions with an adequately shielded syringe or remote handling equipment and maintain adequate shielding around the vial during the useful life of the radioactive product. preparation of dilute sodium iodide i 131 solution 1. using the calibration date and radionuclidic concentration on the label of the product vial, calculate the required volume to produce the necessary dose in mbq or mci. 2. using a shielded syringe, remove the required volume. 3. using the shielded syringe, transfer the required volume to a suitably shielded receiving vial. 4. add diluent to the receiving vial to produce a final dose of the desired volume. 5. the recommended diluent is purified water usp containing 0.2 % sodium thiosulfate usp as a reducing agent. acidic diluents should not be used as they may cause the ph to drop below 7.5 and stimulate the volatilization of iodine i-131 hydriodic acid. 6. present the dose in a shielded container for administration to the patient with a straw. preparation of sodium iodide i 131 capsules 1. use one large gelatin capsule and one small gelatin capsule for each dose to be prepared. each large capsule is empty and each small capsule contains approximately 300 mg of dibasic sodium phosphate anhydrous as the absorbing buffer. 2. using the calibration date and radionuclidic concentration on the label of the sodium iodide i-131 lead shield, calculate the required volume to produce the necessary dose in mbq or mci. 3. open one large capsule by pulling apart the capsule into two pieces as illustrated below: 4. insert an unopened small capsule into the bottom half of the empty large capsule as illustrated below: 5. with an appropriate syringe, withdraw the required volume of sodium iodide i 131 solution (maximum 150 microliters) from the vial as illustrated below: 6. inject into the center of the small capsule through the top as illustrated below: 7. slip the upper half of the large capsule over the bottom half to completely cover the small capsule and push down gently until locked as illustrated below: 8. measure the patient dose in a suitable radioactivity calibration system immediately prior to administration. 9. prepared capsules may be stored in a suitable polypropylene container and place inside a lead pot until use, within seven days. image description image description image description image description image description 2.5 radiation dosimetry the biokinetic modeling and radiation dose distributions associated with thyroid uptake of iodide i 131 depend on dietary intake of stable iodide and presume normal production of thyroid hormone. table 1 shows a range of uptake percentages in an average adult (73.7 kg reference model). table 1 is not intended to be used for treatment planning. for a thyroid blocked from iodide uptake in the production of hormones, the effective half-life of iodide i 131 is approximately 1.4 hours; for "low" to "high" uptake, the effective half-life of i 131 ranges from approximately 80 to 90 hours. table 1 table 1 is not intended for treatment planning. absorbed dose per unit activity sodium iodide i 131 administered orally (mgy/mbq) in adult (73.7-kg reference model) organ thyroid uptake of i 131 (% administered activity a 0 ) 24 h after oral administration blocked thyroid (0% a 0 ) low uptake these columns are not applicable to estimate organ or effective doses in patients following thyroidectomy. in patients with thyroid cancer following thyroidectomy, organ and effective doses can be estimated from the "blocked"-thyroid-uptake values. (16% a 0 ) medium uptake (26% a 0 ) high uptake (36% a 0 ) adrenals 0.044 0.051 0.055 0.059 bone surfaces 0.030 0.089 0.12 0.16 brain 0.021 0.093 0.13 0.17 breast 0.020 0.038 0.048 0.058 gallbladder wall 0.037 0.043 0.046 0.049 gastrointestinal tract esophagus 0.024 0.10 0.14 0.19 stomach wall 0.87 0.77 0.71 0.66 small intestine wall 0.035 0.033 0.032 0.032 colon wall 0.14 0.14 0.14 0.14 (upper large intestine wall) 0.12 0.12 0.12 0.12 (lower large intestine wall) 0.17 0.17 0.17 0.16 heart wall 0.062 0.089 0.10 0.12 kidneys 0.27 0.27 0.27 0.27 liver 0.050 0.093 0.12 0.14 lungs 0.053 0.10 0.13 0.15 muscles 0.026 0.084 0.12 0.15 ovaries 0.038 0.037 0.036 0.035 pancreas 0.060 0.064 0.066 0.068 red marrow 0.031 0.072 0.095 0.12 salivary glands 0.27 0.22 0.19 0.16 skin 0.019 0.043 0.057 0.071 spleen 0.064 0.069 0.072 0.075 testes 0.025 0.024 0.023 0.22 thymus 0.024 0.10 0.14 0.19 thyroid 2.2 280 these values presume unimpeded production of thyroid hormone and may not be applicable to estimate thyroid dose and effective dose in patients who have had previous treatment with i 131 for hyperthyroidism 430 580 urinary bladder wall 0.54 0.45 0.39 0.34 uterus 0.045 0.042 0.040 0.038 remaining organs 0.029 0.084 0.11 0.15 effective dose per administered activity (msv/mbq) 0.28 14 22 29

on, lacrimal gland dysfunction, hypothyroidism, hyperthyroidism, thyrotoxic crisis.( 6 ) to report suspected adverse reactions, contact international isotopes inc. at 1-800-699-3108 or fda at 1-800-fda-1088 or www.fda.gov/medwatch. 6.1 postmarketing experience the following adverse reactions have been reported during post-approval use of sodium iodide i-131 (table 3). because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. table 3 postmarket adverse reactions by system organ class system organ class* symptoms* cardiac disorders chest pain, tachycardia congenital, familial and genetic disorders chromosomal abnormalities, congenital hypothyroidism endocrine disorders hyperthyroidism, hypoparathyroidism, hypothyroidism, thyrotoxic crisis eye disorders lacrimal gland dysfunction gastrointestinal disorders gastritis, nausea, salivary gland dysfunction, sialadenitis, vomiting general disorders and administration site conditions local swelling of thyroid or sites of iodide avid tumor hematologic and lymphatic disorders including fatalities anemia, blood dyscrasia, bone marrow depression, leukopenia, thrombocytopenia immune system disorders bronchospasm neoplasms benign, malignant and unspecified (including cysts and polyps) acute leukemia, solid cancer nervous system disorders +cerebral edema, headache respiratory, thoracic and mediastinal disorders ♦pulmonary fibrosis, ♦radiation pneumonitis skin and subcutaneous tissue disorders hives, itching, rash * in alphabetical order + in patients with iodide-avid brain metastases ♦ in patients with iodide-avid lung metastases

tic thyroid hormones triiodothyronine thyroxine 2 weeks 4 weeks iodide-containing foods: iodized salt, dairy products, egg yolks, seafood, turkey and liver 2 weeks kelp, agar, carrageenan, lugol solution 3 weeks saturated solution of potassium iodide 3 weeks topical iodide (e.g., surgical skin preparation) 3 weeks intravenous radiographic contrast agents water soluble lipophilic 2 months 6 months amiodarone 6 months many drugs and iodine-containing foods interfere with the accumulation of radioiodide by the thyroid. instruct patients to maintain a low-iodide diet (2 weeks) and discontinue anti-thyroid therapy (3 days) before administration. ( 5.8 , 7 )

al capacity and delayed bone age. monitor thyroid function in any infant born after in utero exposure to sodium iodide i 131. data human data sodium iodide i 131 crosses the placenta and the fetal thyroid begins to concentrate iodide during the 10-12 th week of gestation. in literature reports of maternal exposures to sodium iodide i 131 at doses of 333 – 8325 mbq (9 – 225 mci) during 4-26 weeks gestational age, the most common adverse outcomes were hypothyroid infants and children. 8.2 lactation risk summary sodium iodide i-131 solution is contraindicated during lactation because i-131 concentrates in the breast during lactation via the increased expression of the sodium iodide symporter in breast tissue and can lead to hypothyroidism in the infant through breastfeeding. if sodium iodide i-131 is administered postpartum, breastfeeding should not be restarted for the remainder of the postpartum period. in addition, to minimize the absorbed radiation dose to the breast tissue, breastfeeding and breast-pumping should be discontinued for at least 6 weeks before administration of sodium iodide i-131 [see warnings and precautions (5.5) ] . infants exposed to sodium iodide i-131 through breast milk are at risk for development of hypothyroidism because sodium iodide i-131 is distributed into breast milk and may reach concentrations equal to or greater than concentrations in maternal plasma(see data ). data published literature describes sodium iodide i-131 transfer into breast milk and uptake by the thyroid of the breastfed infant. the amount of sodium iodide i-131 detected in the breast milk at 36 to 48 hours after administration is 1% to 27% of the injected dose (with injected doses between 1.1 mbq to 5,143 mbq). 8.3 females and males of reproductive potential sodium iodide i-131 is contraindicated in pregnancy because of the risk of fetal hypothyroidism [see warnings and precautions (5.4) and [see use in specific populations (8.1) ] . pregnancy testing obtain a pregnancy test in females of reproductive potential and verify the absence of pregnancy before initiating treatment [see dosage and administration (2.2) ]. contraception advise females and males of reproductive potential to use effective contraception during treatment with sodium iodide i-131 solution and for at least six months after the last dose of sodium iodide i-131 solution. infertility females fertility may be impaired with sodium iodide i-131 solution treatment. transient amenorrhea and ovarian insufficiency have been observed after sodium iodide i-131 therapy in females. the literature describes reports of transient menstrual cycle irregularities, including amenorrhea, and ovarian failure in females treated with cumulative doses of 1,000 mbq to 59,000 mbq (27 mci to 1,595 mci) sodium iodide i-131. in a published literature analysis, the effects on fertility occurred in up to 30% of women treated with sodium iodide i-131, and may resolve 12 months after treatment. males fertility may be impaired with sodium iodide i-131 solution treatment. discuss sperm banking for males who are expected to receive a high cumulative dose of sodium iodide i-131. transient dose-related impairment of testicular function after sodium iodide i-131 therapy has been reported in the published literature. the literature describes reports of males treated with sodium iodide i-131 at doses of 370 mbq to 22,000 mbq (10 mci to 595 mci) resulting in transiently impaired testicular function (including spermatogenesis). the risk of persistent testicular dysfunction increases after administration of repeated or high cumulative radioiodide exposure. 8.4 pediatric use the safety and effectiveness of sodium iodide i-131 solution have not been established in pediatric patients. pediatric patients are at an increased lifetime risk for malignancy from radiation exposure. 8.5 geriatric use clinical experience has not identified differences in safety or effectiveness in geriatric patients compared to younger patients. however, elderly patients are more likely to have decreased renal function and radiation exposure is greater in patients with impaired renal function [see use in specific populations (8.6) , clinical pharmacology (12.3) ]. 8.6 renal impairment sodium iodide i 131 is primarily excreted by the kidneys. renal function impairment decreases excretion of sodium iodide i 131 and increases the radiation exposure and risk of radiation toxicity. for patients with a history of renal impairment, evaluate renal function for therapeutic planning and consider dosimetry. sodium iodide i 131 is dialyzable. hemodialysis can be used to reduce total body radiation exposure [see clinical pharmacology (12.3) ].

reports of maternal exposures to sodium iodide i 131 at doses of 333 – 8325 mbq (9 – 225 mci) during 4-26 weeks gestational age, the most common adverse outcomes were hypothyroid infants and children.

ds to thyroglobulin resulting in accumulation in the thyroid. the thyroid uptake of iodide is usually increased in hyperthyroidism and in goiter, and is decreased in hypothyroidism. sodium iodide i 131 also accumulates in the stomach, choroid plexus, salivary glands, breast, liver, gall bladder, and kidneys. elimination metabolism in thyroidal follicular cells iodide is oxidized through the action of thyroid peroxidase to iodinium (i + ) which in turn iodinates tyrosine residues of thyroglobulin. excretion sodium iodide i 131 is excreted in urine and feces. the normal range of urinary excretion is 37% to 75% of the administered dose, varying with the thyroid and renal function of the patient. fecal excretion is about 10%.

, varying with the thyroid and renal function of the patient. fecal excretion is about 10%.

pulations (8.1) ] . advise females and males of reproductive potential to use effective contraception during treatment with sodium iodide i 131 and for at least 6 months after the last dose [see warnings and precautions (5.4) , use in specific populations (8.3) ] . advise female patients to contact their healthcare provider with a known or suspected pregnancy. lactation • instruct women to stop breastfeeding and breast-pumping at least 6 weeks prior to sodium iodide i 131 administration [see contraindications (4) , warnings and precautions (5.5) and use in specific populations (8.2) ]. effects on fertility • advise females and males of reproductive potential of the potential for impaired fertility with sodium iodide i-131 treatment [see warnings and precautions (5.6) and use in specific populations (8.3) ]. manufactured by: idaho falls, idaho 83401, usa 1-208-524-5300 www.intisoid.com