sodium iodide 200 MG/ML Injectable Solution

INDICATIONS AND USAGE Sodium Iodide I 131 Capsules Diagnostic is indicated for use in adults for: Assessment of thyroid function using radioactive iodine (RAI) uptake test Imaging the thyroid (scintigraphy) Sodium Iodide I 131 Capsules Diagnostic is a radioactive diagnostic agent indicated for the assessment of thyroid function and for thyroid imaging.

The concentrated sodium iodide I 131 solution provided must be diluted. ( 2.2 ) See Full Prescribing Information for important administration instructions and dilution and preparation instructions for sodium iodide l 131 capsules or oral solution. ( 2.2 , 2.4 ) The recommended dose is based on the thyroid gland uptake as well as the size of the gland: Treatment of Hyperthyroidism: Recommended dosage is 148 to 370 megabecquerels (MBq) [4 to 10 millicuries (mCi). ( 2.3 ) Treatment of Thyroid Carcinoma: Recommended dosage is 1,110 to 33,700 MBq (30 to 100 mCi). ( 2.3 ) 2.1 Radiation Safety Sodium Iodide I-131 is a radioactive drug. Handle with appropriate safety measures to minimize radiation exposure to the patient and healthcare workers [see Warnings and Precautions (5.7) ]: Use only by, or under the direction of, physicians who are qualified by specific training and experience in the safe use and handling of radioactive materials, and whose experience and training have been approved by 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 0.06

WARNINGS AND PRECAUTIONS Radiation-induced thyroiditis may cause or worsen hyperthyroidism. Consider pre-treatment with anti-thyroid medications. ( 5.1 ) Multiple non-thyroid radiation toxicities, including hematopoietic suppression: Individualize dose and monitor for toxicity. ( 5.2 ) Embryo-Fetal toxicity: May cause severe and irreversible hypothyroidism in the neonate. Verify pregnancy status in females of reproductive potential prior to initiating treatment. Females and males of reproductive potential should use effective contraception. ( 5.4 , 8.1 , 8.3 ) Radiation exposure to breast tissue with lactation: Sodium iodide I 131 concentrates in the breast of lactating women. Discontinue breast feeding at least 6 weeks prior to therapy. ( 5.5 , 8.2 ) 5.1 Radiation-induced Thyroiditis Sodium iodide I 131 may cause thyroiditis with gland enlargement and release of thyroid hormone, which may cause or aggravate hyperthyroidism, thyroid storm and thyrotoxic cardiac disease [see Adverse Reactions (6) ] . When treating hyperthyroidism, consider pre-treatment anti-thyroid medication to help deplete the thyroid hormone content within the gland. Discontinue the anti-thyroid medication at least three days 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. 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 to 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 HICON ® 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 HICON ® treatment. Advise females and males of reproductive potential to use effective contraception during treatment with HICON ® and for at least 6 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] . 5.5 Increased Radiation Exposure to Breast Tissue with Lactation HICON ® 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 HICON ® for thyroid carcinoma [see Use in Specific Populations ( 8.3 )]. 5.7 Radiation Exposure to Other Individuals Household Contacts Instruct patients to follow radiation safety precautions after receiving HICON ® 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 HICON ® 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 )] .

CONTRAINDICATIONS HICON ® is contraindicated in: Patients with vomiting and diarrhea [see Warnings and Precautions ( 5.7 )] . Patients with thyroid malignancies shown to have no iodide update, which include the majority of medullary or anaplastic carcinomas. Patients receiving concurrent anti-thyroid therapy [see Warnings and Precautions ( 5.1 ) and Drug Interactions ( 7 )] . Pregnancy [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 )] . Lactation [see Warnings and Precautions ( 5.5 ), Use in Specific Populations ( 8.2 )] . Patients with vomiting and diarrhea. ( 4 ) Patients with thyroid malignancies shown to have no iodide uptake. ( 4 ) Patients receiving concurrent anti-thyroid therapy. ( 4 ) Pregnancy. ( 4 ) Lactation. ( 4 )

CLINICAL PHARMACOLOGY Sodium iodide I-123 is readily absorbed from the upper gastrointestinal tract. Following absorption, the iodide is distributed primarily within the extracellular fluid of the body. It is trapped and organically bound by the thyroid and concentrated by the stomach, choroid plexus and salivary glands. It is excreted by the kidneys. The fraction of the administered dose which is accumulated in the thyroid gland may be a measure of thyroid function in the absence of unusually high or low iodine intake or administration of certain drugs which influence iodine accumulation by the thyroid gland. Accordingly, the patient should be questioned carefully regarding previous medications and/or procedures involving radiographic media. Normal subjects can accumulate approximately 10 to 50% of the administered iodine dose in the thyroid gland, however, the normal and abnormal ranges are established by individual physician's criteria. The mapping (imaging) of sodium iodide I-123 distribution in the thyroid gland may provide useful information concerning thyroid anatomy and definition of normal and/or abnormal functioning of tissue within the gland.