LEVOXYL

WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS Thyroid hormones, including LEVOXYL, 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) , Overdosage (10) ] . WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS See full prescribing information for complete boxed warning. Thyroid hormones, including LEVOXYL, 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 , 7.7 , 10 ).

5 WARNINGS AND PRECAUTIONS Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate LEVOXYL at less than the full replacement dose because of the increased risk of cardiac adverse reactions, including atrial fibrillation. ( 2.3 , 5.1 , 8.5 ) Myxedema coma: Do not use oral thyroid hormone drug products to treat myxedema coma. ( 5.2 ) Acute adrenal crisis in patients with concomitant adrenal insufficiency: Treat with replacement glucocorticoids prior to initiation of LEVOXYL treatment. ( 5.3 ) Prevention of hyperthyroidism or incomplete treatment of hypothyroidism: Proper dose titration and careful monitoring is critical to prevent the persistence of hypothyroidism or the development of hyperthyroidism. ( 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 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 LEVOXYL 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) , Use in Specific Populations (8.5) ] . Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive LEVOXYL therapy. Monitor patients receiving concomitant LEVOXYL and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiovascular symptoms develop or worsen, reduce or withhold the LEVOXYL dose for one week and restart at a lower dose. 5.2 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. 5.3 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 LEVOXYL [see Contraindications (4) ] . 5.4 Prevention of Hyperthyroidism or Incomplete Treatment of Hypothyroidism LEVOXYL has a narrow therapeutic index. Over- or undertreatment with LEVOXYL may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and on glucose and lipid metabolism. Titrate the dose of LEVOXYL carefully and monitor response to titration to avoid these effects [see Dosage and Administration (2.4) ] . Monitor for the presence of drug or food interactions when using LEVOXYL and adjust the dose as necessary [see Drug Interactions (7) , Clinical Pharmacology (12.3) ] . 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 LEVOXYL [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 LEVOXYL that achieves the desired clinical and biochemical response to mitigate against this risk.

6 ADVERSE REACTIONS Common adverse reactions with LEVOXYL therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5.4) , 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 and cramps 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 : hair loss, flushing Endocrine : decreased bone mineral density Reproductive : menstrual irregularities, impaired fertility Seizures have been reported rarely with levothyroxine therapy. Common adverse reactions for LEVOXYL are primarily those of hyperthyroidism due to therapeutic overdosage: 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 Pfizer, Inc. at 1-800-438-1985 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 and premature closure of the epiphysis in pediatric patients 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 gastrointestinal symptoms (abdominal pain, nausea, vomiting, and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur. Choking and Gagging on LEVOXYL Tablets There have been reports of choking, gagging, tablet stuck in throat, and dysphagia with LEVOXYL tablets, predominately when LEVOXYL tablets were not taken with water [see Dosage and Administration (2.1) ] .