Drug Label

Uses

1 INDICATIONS AND USAGE Sodium Iodide I 131 Capsules Therapeutic is indicated for the treatment of hyperthyroidism and thyroid carcinomas that take up iodide. Palliative effects may be observed in patients with advanced thyroid malignancy if the metastatic lesions take up iodide. Sodium Iodide I 131 Capsules Therapeutic is a radioactive therapeutic agent indicated for the treatment of hyperthyroidism and thyroid carcinomas that take up iodine. Palliative effects may be observed in patients with advanced thyroid malignancy if the metastatic lesions take up iodine. ( 1 )

Dosage & Administration

2 DOSAGE AND ADMINISTRATION Use safe handling measures to minimize inadvertent radiation exposure. ( 2.1 ) Hyperthyroidism 148 to 370 megabecquerels (MBq) (4 to 10 millicuries, mCi). Toxic nodular goiter and other situations may require larger doses. ( 2.2 ) Thyroid Carcinoma For thyroid carcinoma, 3700 to 5550 MBq (100 to 150 mCi). ( 2.3 ) For post-operative ablation of normal thyroid tissue: 1850 MBq (50 mCi). ( 2.3 ) Individualize therapy, including dose selection, based upon patient-specific factors detected during the therapeutic planning process. ( 2.4 ) 2.1 Radiation Safety Sodium iodide I-131 capsules emit radiation and must be handled with safety measures to minimize inadvertent radiation exposure to clinical personnel and patients [see Warnings and Precautions ( 5.7 )] . Radiopharmaceuticals should be used only by or under the direction of physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. Wear waterproof gloves during the entire sodium iodide I-131 capsule handling and administration procedure. Maintain adequate shielding during the radiation-emitting life of the product. Measure the patient dose using a suitable radioactivity calibration system immediately prior to administration. 2.2 Hyperthyroidism For hyperthyroidism, the usual sodium iodide I-131 dose range is 148 to 370 MBq (4 to 10 mCi). Higher doses may be necessary for the treatment of toxic nodular goiter and other special situations. Consider discontinuation of anti-thyroid therapy in a severely hyperthyroid patient three to four days before administration of sodium iodide I-131. Evaluate patients for risk of thyroid enlargement and obstruction of structures in the neck [see Warnings and Precautions ( 5.1 , 5.2 )] . 2.3 Thyroid Carcinoma For thyroid carcinoma, the usual sodium iodide I-131 therapeutic dose is 3700 to 5550 MBq (100 to 150 mCi). For ablation of post-operative residual thyroid tissue, the usual dose is 1850 MBq (50 mCi). 2.4 Individualization of Therapy Individualize sodium iodide I-131 therapy, including dose selection, based upon patient-specific factors such as the nature of the underlying condition, co-morbidities, age, estimated thyroid tissue iodine uptake, thyroid size, as well as ability of the patient to comply with the therapeutic regimen and radiation safety procedures. Perform a clinical assessment, including history, physical examination and laboratory testing when preparing patients for sodium iodide I-131 therapy in order to detect conditions which may alter thyroid iodine uptake and increase the risks of the therapy or diminish its effectiveness. For example, intake of iodine in radiographic contrast may diminish thyroid iodine uptake while low serum chloride or nephrosis may increase thyroid iodine uptake. Obtain a drug history and ascertain whether any medications need to be withheld before the administration of the therapy [see Drug Interactions ( 7 )] . 2.5 Radiation Dosimetry The estimated absorbed radiation doses 1 to an average (70 kg) euthyroid (normal functioning thyroid) patient from an oral dose of iodine-131 in both milligray (mGy) per megabecquerel (MBq) and rad per millicurie (mCi) are shown in Table 1. Table 1. Absorbed Radiation Doses Tissue Thyroid Uptake 5% 15% 25% mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi Thyroid 72 266 210 777 360 1300 Stomach Wall 0.45 1.7 0.46 1.7 0.46 1.7 Red Marrow 0.038 0.14 0.054 0.20 0.07 0.26 Liver 0.03 0.11 0.032 0.12 0.035 0.13 Testes 0.029 0.11 0.028 0.10 0.027 0.10 Ovaries 0.044 0.16 0.043 0.16 0.043 0.16 Urinary Bladder 0.58 2.1 0.52 1.9 0.46 1.7 Salivary Glands 2 0.5 1.85 0.5 1.85 0.5 1.85 Other 0.040 0.15 0.065 0.24 0.090 0.33 2.1 Radiation Safety Sodium iodide I-131 capsules emit radiation and must be handled with safety measures to minimize inadvertent radiation exposure to clinical personnel and patients [see Warnings and Precautions ( 5.7 )] . Radiopharmaceuticals should be used only by or under the direction of physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. Wear waterproof gloves during the entire sodium iodide I-131 capsule handling and administration procedure. Maintain adequate shielding during the radiation-emitting life of the product. Measure the patient dose using a suitable radioactivity calibration system immediately prior to administration. 2.2 Hyperthyroidism For hyperthyroidism, the usual sodium iodide I-131 dose range is 148 to 370 MBq (4 to 10 mCi). Higher doses may be necessary for the treatment of toxic nodular goiter and other special situations. Consider discontinuation of anti-thyroid therapy in a severely hyperthyroid patient three to four days before administration of sodium iodide I-131. Evaluate patients for risk of thyroid enlargement and obstruction of structures in the neck [see Warnings and Precautions ( 5.1 , 5.2 )] . 2.3 Thyroid Carcinoma For thyroid carcinoma, the usual sodium iodide I-131 therapeutic dose is 3700 to 5550 MBq (100 to 150 mCi). For ablation of post-operative residual thyroid tissue, the usual dose is 1850 MBq (50 mCi). 2.4 Individualization of Therapy Individualize sodium iodide I-131 therapy, including dose selection, based upon patient-specific factors such as the nature of the underlying condition, co-morbidities, age, estimated thyroid tissue iodine uptake, thyroid size, as well as ability of the patient to comply with the therapeutic regimen and radiation safety procedures. Perform a clinical assessment, including history, physical examination and laboratory testing when preparing patients for sodium iodide I-131 therapy in order to detect conditions which may alter thyroid iodine uptake and increase the risks of the therapy or diminish its effectiveness. For example, intake of iodine in radiographic contrast may diminish thyroid iodine uptake while low serum chloride or nephrosis may increase thyroid iodine uptake. Obtain a drug history and ascertain whether any medications need to be withheld before the administration of the therapy [see Drug Interactions ( 7 )] . 2.5 Radiation Dosimetry The estimated absorbed radiation doses 1 to an average (70 kg) euthyroid (normal functioning thyroid) patient from an oral dose of iodine-131 in both milligray (mGy) per megabecquerel (MBq) and rad per millicurie (mCi) are shown in Table 1. Table 1. Absorbed Radiation Doses Tissue Thyroid Uptake 5% 15% 25% mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi mGy/ MBq rads/ mCi Thyroid 72 266 210 777 360 1300 Stomach Wall 0.45 1.7 0.46 1.7 0.46 1.7 Red Marrow 0.038 0.14 0.054 0.20 0.07 0.26 Liver 0.03 0.11 0.032 0.12 0.035 0.13 Testes 0.029 0.11 0.028 0.10 0.027 0.10 Ovaries 0.044 0.16 0.043 0.16 0.043 0.16 Urinary Bladder 0.58 2.1 0.52 1.9 0.46 1.7 Salivary Glands 2 0.5 1.85 0.5 1.85 0.5 1.85 Other 0.040 0.15 0.065 0.24 0.090 0.33

Warnings & Cautions

5 WARNINGS AND PRECAUTIONS Radiation-induced thyroiditis: may cause or worsen hyperthyroidism; consider pre-treatment with anti-thyroid medications. ( 5.1 ) Thyroid enlargement, including that due to thyroid stimulating hormone concomitant therapy, may obstruct structures in the neck. Evaluate patients at high risk. ( 5.2 ) Multiple non-thyroid radiation toxicities have been reported following sodium iodide I-131 therapy, including increased risks for neoplasia, hematopoietic suppression, and fetal or reproductive toxicity. Individualize dosage, verify absence of pregnancy, monitor patients for toxicity, and advise patients on contraceptive use. ( 5.3 , 5.5 , 5.6 ) 5.1 Radiation-induced Thyroiditis Sodium iodide I-131 may cause thyroiditis with gland enlargement and release of thyroid hormone, particularly when used to treat hyperthyroidism. The thyroiditis may cause or worsen hyperthyroidism, and may cause thyroid storm. When treating hyperthyroidism, consider pre-treatment with 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. Consider beta-blocker therapy before administration of sodium iodide I-131 to minimize the risk of hyperthyroidism and thyroid storm. 5.2 Thyroid-stimulating Hormone (TSH) and Thyroid Enlargement Enhanced TSH secretion, e.g., following discontinuation of anti-thyroid medications, or the administration of TSH to enhance sodium iodide I-131 uptake, may cause thyroid enlargement and obstructive complications of the trachea, esophagus, or blood vessels in the neck. Evaluate patients at high risk of obstructive complications before preparative treatments known to cause thyroid enlargement. 5.3 Radiation-induced Toxicities Radiation-induced toxicities, including dose-dependent fatalities, have been reported following sodium iodide I-131 therapy. Post-marketing reports have identified an increased risk for neoplasia, as well as risks for hematopoietic suppression. Salivary and lacrimal gland toxicity is relatively common and may manifest as conjunctivitis, xerophthalmia, epiphora, sialadenitis and xerostomia [see Adverse Reactions ( 6 )] . 5.4 Hypersensitivity Reactions Hypersensitivity reactions, including rash and hives have been reported following administration of sodium iodide I-131. Sodium iodide I-131 capsules may contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. During the pre-therapy assessment, question patients about a history of hypersensitivity to sulfite [see Adverse Reactions ( 6 )] . 5.5 Fetal Risk Transplacental passage of sodium iodide I-131 can cause severe and possibly irreversible hypothyroidism in neonates [see Contraindications ( 4 )] . Females and Males of Childbearing Potential When planning sodium iodide I-131 therapy for women of childbearing potential, obtain a pregnancy test and verify the absence of a pregnancy before initiating treatment. Advise women and men of childbearing potential to use two effective methods of contraception to avoid pregnancy for at least six months after sodium iodide I-131 administration. Advise patients of the potential need to use two effective methods of contraception to avoid pregnancy for an even longer period of time (e.g., one year) if additional sodium iodide I-131 therapy or radionuclide imaging is anticipated. 5.6 Transient Infertility Transient, dose-related impairment of testicular function has been reported after sodium iodide I-131 therapy. Consider sperm banking for men who are anticipated to receive a high cumulative sodium iodide I-131 dose (e.g., greater than 14 GBq). In females, transient ovarian failure has been observed after sodium iodide I-131 therapy. 5.7 Radiation Exposure Risk to Other Individuals Unwanted radiation exposure can occur from handling and administration of radiopharmaceuticals or from contaminated waste products, including urine and feces. Follow safe administration instructions to minimize unnecessary radiation exposure to patients and health care workers [see Dosage and Administration ( 2.1 )] . Instruct patients on how to reduce unnecessary radiation exposure to others, especially family members following treatment. Review the most recent professional society guidelines and publications that describe the procedures for the safe use of sodium iodide I-131 therapy to minimize radiation toxicity risks to patients, radiation exposure risks to other individuals, and environmental radiation contamination risks. 5.1 Radiation-induced Thyroiditis Sodium iodide I-131 may cause thyroiditis with gland enlargement and release of thyroid hormone, particularly when used to treat hyperthyroidism. The thyroiditis may cause or worsen hyperthyroidism, and may cause thyroid storm. When treating hyperthyroidism, consider pre-treatment with 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. Consider beta-blocker therapy before administration of sodium iodide I-131 to minimize the risk of hyperthyroidism and thyroid storm. 5.2 Thyroid-stimulating Hormone (TSH) and Thyroid Enlargement Enhanced TSH secretion, e.g., following discontinuation of anti-thyroid medications, or the administration of TSH to enhance sodium iodide I-131 uptake, may cause thyroid enlargement and obstructive complications of the trachea, esophagus, or blood vessels in the neck. Evaluate patients at high risk of obstructive complications before preparative treatments known to cause thyroid enlargement. 5.3 Radiation-induced Toxicities Radiation-induced toxicities, including dose-dependent fatalities, have been reported following sodium iodide I-131 therapy. Post-marketing reports have identified an increased risk for neoplasia, as well as risks for hematopoietic suppression. Salivary and lacrimal gland toxicity is relatively common and may manifest as conjunctivitis, xerophthalmia, epiphora, sialadenitis and xerostomia [see Adverse Reactions ( 6 )] . 5.4 Hypersensitivity Reactions Hypersensitivity reactions, including rash and hives have been reported following administration of sodium iodide I-131. Sodium iodide I-131 capsules may contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. During the pre-therapy assessment, question patients about a history of hypersensitivity to sulfite [see Adverse Reactions ( 6 )] . 5.5 Fetal Risk Transplacental passage of sodium iodide I-131 can cause severe and possibly irreversible hypothyroidism in neonates [see Contraindications ( 4 )] . Females and Males of Childbearing Potential When planning sodium iodide I-131 therapy for women of childbearing potential, obtain a pregnancy test and verify the absence of a pregnancy before initiating treatment. Advise women and men of childbearing potential to use two effective methods of contraception to avoid pregnancy for at least six months after sodium iodide I-131 administration. Advise patients of the potential need to use two effective methods of contraception to avoid pregnancy for an even longer period of time (e.g., one year) if additional sodium iodide I-131 therapy or radionuclide imaging is anticipated. 5.6 Transient Infertility Transient, dose-related impairment of testicular function has been reported after sodium iodide I-131 therapy. Consider sperm banking for men who are anticipated to receive a high cumulative sodium iodide I-131 dose (e.g., greater than 14 GBq). In females, transient ovarian failure has been observed after sodium iodide I-131 therapy. 5.7 Radiation Exposure Risk to Other Individuals Unwanted radiation exposure can occur from handling and administration of radiopharmaceuticals or from contaminated waste products, including urine and feces. Follow safe administration instructions to minimize unnecessary radiation exposure to patients and health care workers [see Dosage and Administration ( 2.1 )] . Instruct patients on how to reduce unnecessary radiation exposure to others, especially family members following treatment. Review the most recent professional society guidelines and publications that describe the procedures for the safe use of sodium iodide I-131 therapy to minimize radiation toxicity risks to patients, radiation exposure risks to other individuals, and environmental radiation contamination risks.

Pregnancy

8.1 Pregnancy Pregnancy Category X [see Warnings and Precautions ( 5.5 )] .

Nursing Mothers

8.3 Nursing Mothers Sodium iodide I-131 is excreted into human milk and may reach concentrations equal to or greater than concentrations in maternal plasma. To minimize the absorbed radiation dose to the breast tissue, breastfeeding and breast-pumping should be discontinued for at least four weeks before administration of sodium iodide I-131. Sodium iodide I-131 is contraindicated in pregnancy; if sodium iodide I-131 is administered in the postpartum period, the lactating mother should not breast-feed the infant. Breastfeeding may resume with the birth of another child, if the mother does not receive sodium iodide I-131 during that postpartum period.

Pediatric Use

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Published reports suggest that the thyroid gland of pediatric patients is more sensitive to the effects of sodium iodide I-131; however, it is unknown if the I-131 dose-response relationship is similar to that of adults. When considering the use of sodium iodide I-131 in pediatric patients, the risks, particularly carcinogenic risks, and benefits of sodium iodide I-131 must be carefully weighed against those of other possible treatments.

Geriatric Use

8.5 Geriatric Use Because elderly patients are more likely to have decreased renal function and co-morbid conditions, enhanced evaluation, dose-selection consideration and follow-up may be necessary for elderly patients receiving sodium iodide I-131 therapy, compared to younger patients [see Use in Specific Populations ( 8.6 )] . When treating hyperthyroidism in geriatric patients at risk of developing cardiac complications, pre-treatment and post-treatment with anti-thyroid drugs and/or beta-blockers may help minimize the risk of excessive post-treatment hyperthyroidism due to radiation-induced thyroiditis [see Warnings and Precautions ( 5.1 )] .

Side Effects

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Radiation-induced Thyroiditis [see Warnings and Precautions ( 5.1 )] Thyroid-stimulating Hormone and Thyroid Enlargement [see Warnings and Precautions ( 5.2 )] Radiation-induced Toxicities [see Warnings and Precautions ( 5.3 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] Fetal Risk [see Warnings and Precautions ( 5.5 )] Transient Infertility [see Warnings and Precautions ( 5.6 )] Radiation Exposure to Other Individuals [see Warnings and Precautions ( 5.7 )] Radiation-related adverse reactions are a function of the dose level received by the patient. The following adverse reactions have been reported with doses of sodium iodide I-131 used in the treatment of benign disease, such as hyperthyroidism: Gastrointestinal disorders: sialadenitis Cardiac disorders: chest pain and tachycardia Skin and subcutaneous tissue disorders: iododerma, itching skin, rash, and hives Endocrine disorders: hypothyroidism, hyperthyroidism, thyrotoxic crisis, hypoparathyroidism General disorders and administration site conditions: local swelling The following adverse reactions have been reported with doses of sodium iodide I-131 used in the treatment of malignant disease: Blood and lymphatic system disorders including fatalities: radiation sickness, bone marrow depression, anemia, leucopenia, thrombocytopenia, and blood dyscrasia Neoplasms benign, malignant and unspecified (including cysts and polyps): leukemia and solid cancers Eye disorders: lacrimal gland dysfunction Gastrointestinal disorders: salivary gland dysfunction, nausea, vomiting Congenital, familial and genetic disorders: congenital hypothyroidism and chromosomal abnormalities Adverse reactions that occur after treatment of benign disease may also occur after treatment of malignant disease. Tenderness, pain on swallowing, sore throat, and cough have been reported, generally around the third day after sodium iodide I-131 administration. Adverse reactions that have been reported with doses of sodium iodide I-131 used in the treatment of benign disease include sialadenitis, chest pain, tachycardia, iododerma, itching skin, rash, hives, hypothyroidism, hyperthyroidism, thyrotoxic crisis, hypoparathyroidism, and local swelling. ( 6 ) Adverse reactions that have been reported with doses of sodium iodide I-131 used in the treatment of malignant disease include radiation sickness, bone marrow depression, anemia, leucopenia, thrombocytopenia, blood dyscrasia, leukemia, solid cancers, lacrimal gland dysfunction, salivary gland dysfunction, congenital hypothyroidism, and chromosomal abnormalities. ( 6 ) To report SUSPECTED ADVERSE REACTIONS contact Mallinckrodt Inc. at 1-888-744-1414 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Drug Interactions

7 DRUG INTERACTIONS Many pharmacologic agents interact with sodium iodide I-131. These agents may affect the iodide protein binding and alter the iodide pharmacokinetics and pharmacodynamics. Table 3. Drug Interactions Substance Average Duration of Effect Anti-thyroid drugs e.g., carbimazole, propylthiouracil 5 days Natural or synthetic thyroid hormone e.g., thyroxine tri-iodothyronine 4 weeks 2 weeks Iodine-containing medications e.g., amiodarone expectorants, vitamins 4 weeks 2 weeks Topical iodide 1-9 months X-ray contrast agents iodine-containing agents Up to 1 year Other drugs anticoagulants, antihistamines corticosteroids, sulfonamides tolbutamide, perchlorate phenylbutazone lithium 1 week 1 week 1 week 1-2 weeks 4 weeks Many pharmacologic agents are known to interact with radioiodide. See full prescribing information complete list. ( 7 )

Contraindications

4 CONTRAINDICATIONS Sodium Iodide I 131 Capsules Therapeutic is contraindicated in: Patients with vomiting and diarrhea [see Warnings and Precautions ( 5.7 )] . The treatment of thyroid malignancies shown to have no iodide uptake, which include the majority of medullary and anaplastic carcinomas. Pregnancy [see Warnings and Precautions ( 5.5 )] . Breastfeeding [see Use in Specific Populations ( 8.3 )] .

Overdose

10 OVERDOSAGE In case of exposure to a radioactive dose of sodium iodide I-131 exceeding the intended therapeutic dose provide general supportive care, monitor for bone marrow and thyroid suppression and consider administering a thyroid blocking agent such as potassium iodide (KI) or perchlorate promptly within 4 to 6 hours after the exposure. Thyroid blockade may reduce radiation exposure of thyroid tissue but would not prevent radiation injury to the rest of the body. Assess the benefit of administering a blocking agent against the risk of failure of sodium iodide I-131 therapy.