FDA label ca2a90c4-a855-445e-8ddc-625fdbae574a

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 )] .

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 )] Most reported reactions were manifestations of radiation toxicity and were related to sodium iodide I-131 dose, and patient-specific factors, such as the location of metastatic lesions and co-morbid conditions. Common adverse reactions to sodium iodide I-131 therapy include: Gastrointestinal: nausea and vomiting Cardiovascular: chest pain and tachycardia Allergic: itching skin, rash, and hives The following adverse reactions have been reported with large doses of sodium iodide I-131: Hematopoietic toxicities including fatalities: radiation sickness, bone marrow depression, anemia, leucopenia, thrombocytopenia, blood dyscrasia, and chromosomal abnormalities Malignancies: leukemia; stomach, bladder and breast cancer Published reports have described salivary and lacrimal gland dysfunction. Tenderness and swelling of the neck, pain on swallowing, sore throat, and cough have been reported, generally around the third day after sodium iodide I-131 administration [see Warnings and Precautions ( 5.4 )] . Common adverse reactions are: nausea, vomiting, chest pain, tachycardia, itching skin, rash and hives. ( 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