Cytomel®(liothyronine sodium)

1 INDICATIONS AND USAGE CYTOMEL is an L-triiodothyronine (T3) indicated for:

• Hypothyroidism: As replacement in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism (1.1)
• Pituitary Thyroid-Stimulating Hormone (TSH) Suppression: As an adjunct to surgery and radioiodine therapy in the management of well-differentiated thyroid cancer (1.2)
• Thyroid Suppression Test: As a diagnostic agent in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy (1.3)

Limitations of Use: - Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients. (1) - Not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis. (1)

1.1 Hypothyroidism CYTOMEL is indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

1.2 Pituitary Thyroid-Stimulating Hormone (TSH) Suppression CYTOMEL is indicated as an adjunct to surgery and radioiodine therapy in the management of well-differentiated thyroid cancer.

1.3 Thyroid Suppression Test CYTOMEL is indicated as a diagnostic agent in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy.

Limitations of Use

• CYTOMEL is not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients as there are no clinical benefits and overtreatment with CYTOMEL may induce hyperthyroidism.
• CYTOMEL is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.

4 CONTRAINDICATIONS CYTOMEL is contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)]. Uncorrected adrenal cortical insufficiency (4)

5 WARNINGS AND PRECAUTIONS

• Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate CYTOMEL 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 CYTOMEL 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 thyroid hormone 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 CYTOMEL therapy in this population at lower doses than those recommended in younger individuals or in patients without cardiac disease. Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive CYTOMEL therapy. Monitor patients receiving concomitant CYTOMEL and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiovascular symptoms develop or worsen, reduce or withhold the CYTOMEL 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 thyroid hormone 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 CYTOMEL.

5.4 Prevention of Hyperthyroidism or Incomplete Treatment of Hypothyroidism CYTOMEL has a narrow therapeutic index. Over- or undertreatment with CYTOMEL 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 CYTOMEL carefully and monitor response to titration to avoid these effects.

5.5 Worsening of Diabetic Control Addition of thyroid hormone 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 CYTOMEL.

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 thyroid hormone 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 CYTOMEL that achieves the desired clinical and biochemical response to mitigate against this risk.

6 ADVERSE REACTIONS Adverse reactions associated with CYTOMEL therapy are primarily those of hyperthyroidism due to therapeutic overdosage. 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 Most common adverse reactions for CYTOMEL are primarily those of hyperthyroidism due to therapeutic overdosage: arrhythmias, myocardial infarction, dyspnea, 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 thyroid replacement therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses 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.

11 DESCRIPTION CYTOMEL tablets contain the active ingredient, liothyronine (L-triiodothyronine or LT3), a synthetic form of a thyroid hormone liothyronine in sodium salt form. It is chemically designated as L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-, monosodium salt. CYTOMEL tablets contain liothyronine sodium equivalent to liothyronine in 5 mcg, 25 mcg, and 50 mcg. Inactive ingredients consist of calcium sulfate, corn starch, gelatin, stearic acid, sucrose and talc.