Levothyroxine Sodium

WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS Thyroid hormones, including Levothyroxine Sodium Injection, should not be used for the treatment of obesity or for weight loss. Larger doses may produce serious or even life threatening manifestations of toxicity. ( 6 , 10 ) WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS Thyroid hormones, including Levothyroxine Sodium Injection, should not be used for the treatment of obesity or for weight loss. Larger doses may produce serious or even life threatening manifestations of toxicity. ( 6 , 10 )

5 WARNINGS AND PRECAUTIONS • Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease: Overtreatment may cause arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death, particularly in patients with cardiovascular disease and in elderly patients. Start with lower doses in elderly patients and in patients with underlying cardiovascular disease and monitor patients after administration ( 5.1 ). • Acute Adrenal Crisis in Patients with Concomitant Adrenal Insufficiency: Initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy may precipitate an acute adrenal crisis in patients with adrenal insufficiency. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment ( 5.2 ). • Worsening of Diabetic Control: May worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control ( 5.3 ). 5.1 Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease Overtreatment with Levothyroxine Sodium Injection may cause arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death, particularly in patients with cardiovascular disease and in elderly patients. Start with lower doses in elderly patients and in patients with underlying cardiovascular disease and monitor patients after administration of Levothyroxine Sodium Injection for cardiac adverse reactions. 5.2 Acute Adrenal Crisis in Patients with Concomitant Adrenal Insufficiency Chronic autoimmune thyroiditis, which can lead to myxedema coma, may occur in association with other autoimmune disorders such as adrenal insufficiency. Thyroid hormone increases metabolic clearance of glucocorticoids. Initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy may precipitate an acute adrenal crisis in patients with adrenal insufficiency [see Contraindications ( 4 )]. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with Levothyroxine Sodium Injection. 5.3 Worsening of Diabetic Control Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control [see Drug Interactions ( 7.2 )].

6 ADVERSE REACTIONS Adverse reactions associated with levothyroxine are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions ( 5 ) , Overdosage ( 10 ) ] . They include the following: • General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating • Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia • Musculoskeletal: tremors, muscle weakness, muscle spasm • Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest • Respiratory: dyspnea • Gastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests • Dermatologic: flushing, rash Seizures have been reported rarely with the institution of levothyroxine therapy. Adverse reactions associated with Levothyroxine Sodium Injection are primarily those of hyperthyroidism due to therapeutic overdosage: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating, headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia, tremors, muscle weakness, muscle spasm, palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest, dyspnea, diarrhea, vomiting, abdominal cramps, elevations in liver function tests, flushing, and rash. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Hypersensitivity Reactions Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.