Tirosint SOL

WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS Thyroid hormones, including TIROSINT-SOL, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects [see Adverse Reactions (6) , Drug Interactions (7.7) , and Overdosage (10) ]. WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS See full prescribing information for complete boxed warning Thyroid hormones, including TIROSINT-SOL, should not be used for the treatment of obesity or for weight loss. Doses beyond the range of daily hormonal requirements may produce serious or even life threatening manifestations of toxicity ( 6 , 10 ).

5 WARNINGS AND PRECAUTIONS Serious risks related to overtreatment or undertreatment with TIROSINT-SOL: Titrate the dose of TIROSINT-SOL carefully and monitor response to titration. ( 5.1 ) Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease : Initiate TIROSINT-SOL at less than the full replacement dose because of the increased risk of cardiac adverse reactions, including atrial fibrillation. ( 2.3 , 5.2 , 8.5 ) Myxedema coma: Do not use oral thyroid hormone drug products to treat myxedema coma. ( 5.3 ) Acute adrenal crisis in patients with concomitant adrenal insufficiency: Treat with replacement glucocorticoids prior to initiation of TIROSINT‑SOL treatment. ( 5.4 ) Worsening of diabetic control: therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing, or discontinuing thyroid hormone therapy. ( 5.5 ) Decreased bone mineral density associated with thyroid hormone over-replacement: Over-replacement can increase bone resorption and decrease bone mineral density. Give the lowest effective dose. 5.6 ) 5.1 Serious Risks Related to Overtreatment or Undertreatment with TIROSINT-SOL TIROSINT-SOL has a narrow therapeutic index. Overtreatment or undertreatment with TIROSINT-SOL may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, gastrointestinal function, and glucose and lipid metabolism in adult or pediatric patients. In pediatric patients with congenital and acquired hypothyroidism, undertreatment may adversely affect cognitive development and linear growth, and overtreatment is associated with craniosynostosis and acceleration of bone age [see Use in Specific Populations (8.4)]. Titrate the dose of TIROSINT-SOL carefully and monitor response to titration to avoid these effects [see Dosage and Administration (2.4)]. Consider the potential for food or drug interactions and adjust the administration or dosage of TIROSINT-SOL as needed [see Dosage and Administration (2.4), Drug Interactions (7.1), and Clinical Pharmacology (12.3)]. 5.2 Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease Overtreatment with levothyroxine may cause an increase in heart rate, cardiac wall thickness, and cardiac contractility, and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. Initiate TIROSINT-SOL therapy in this population at lower doses than those recommended in younger individuals or in patients without cardiac disease [see Dosage and Administration (2.3) and Use in Specific Populations (8.5) ]. Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive TIROSINT-SOL therapy. Monitor patients receiving concomitant TIROSINT-SOL and sympathomimetic agents for signs and symptoms of coronary insufficiency . If cardiac symptoms develop or worsen, reduce the TIROSINT-SOL dose or withhold it for one week and restart at a lower dose. 5.3 Myxedema Coma Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, and may result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract. Use of oral thyroid hormone drug products is not recommended to treat myxedema coma. Administer thyroid hormone products formulated for intravenous administration to treat myxedema coma. 5.4 Acute Adrenal Crisis in Patients with Concomitant 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. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with TIROSINT-SOL [see Contraindications (4)]. 5.5 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 after starting, changing, or discontinuing TIROSINT-SOL [see Drug Interactions (7.2) ] . 5.6 Decreased Bone Mineral Density Associated with Thyroid Hormone Over-Replacement Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in post-menopausal women. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase, and suppressed serum parathyroid hormone levels. Administer the minimum dose of TIROSINT-SOL that achieves the desired clinical and biochemical response to mitigate this risk.

6 ADVERSE REACTIONS Adverse reactions associated with TIROSINT-SOL therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5) and 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 (GI): diarrhea, vomiting, abdominal cramps, elevations in liver function tests Dermatologic: hair loss, flushing, rash Endocrine: decreased bone mineral density Reproductive: menstrual irregularities, impaired fertility Seizures have been reported rarely with the institution of levothyroxine therapy. Adverse reactions associated with TIROSINT-SOL are primarily those of hyperthyroidism due to therapeutic overdosage including: arrhythmias, myocardial infarction, dyspnea, muscle spasm, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact IBSA Pharma Inc. at 1-800-587-3513, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Adverse Reactions in Pediatric Patients Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants who have not undergone closure of the fontanelles, and in premature closure of the epiphyses in pediatric patients still experiencing growth with resultant compromised adult height. 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 GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.