Liothyronine (liothyronine)

1 INDICATIONS AND USAGE Liothyronine sodium 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 Liothyronine sodium 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 Liothyronine sodium is indicated as an adjunct to surgery and radioiodine therapy in the management of well-differentiated thyroid cancer . 1.3 Thyroid Suppression Test Liothyronine sodium is indicated as a diagnostic agent in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy. Limitations of Use • Liothyronine sodium 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 liothyronine sodium may induce hyperthyroidism [see Warnings and Precautions (5.4) ] . • Liothyronine sodium is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.

2 DOSAGE AND ADMINISTRATION • Administer liothyronine sodium orally once daily and individual dosage according to patient response and laboratory findings ( 2.1 ) • See full prescribing information for recommended dosage for hypothyroidism ( 2.2 ) TSH suppression in well-differentiated thyroid cancer ( 2.3 ) and for thyroid suppression test ( 2.4 ) • When switching a patient to liothyronine sodium, discontinue levothyroxine therapy and initiate liothyronine sodium at a low dosage. Gradually increase the dose according to the patient's response ( 2.5 ) • Adequacy of therapy determined with periodic monitoring of TSH and T3 levels as well as clinical status ( 2.6 ) 2.1 General Principles of Dosing The dose of liothyronine sodium for hypothyroidism or pituitary TSH suppression depends on a variety of factors including: the patient's age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food and the specific nature of the condition being treated [see Dosage and Administration (2.2 , 2.3 , 2.4 ), Warnings and Precautions (5) , and Drug Interactions (7) ] . Dosing must be individualized to account for these factors and dose adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters [see Dosage and Administration (2.4) ] . Administer liothyronine sodium tablets orally once daily. 2.2 Recommended Dosage for Hypothyroidism Adults The recommended starting dosage is 25 mcg orally once daily. Increase the dose by 25 mcg daily every 1 or 2 weeks, if needed. The usual maintenance dose is 25 mcg to 75 mcg once daily. For elderly patients or patients with underlying cardiac disease, start with liothyronine sodium 5 mcg once daily and increase by 5 mcg increments at the recommended intervals. Serum TSH is not a reliable measure of liothyronine sodium dose adequacy in patients with secondary or tertiary hypothyroidism and should not be used to monitor therapy. Use the serum T3 level to monitor adequacy of therapy in this patient population. Pediatric Patients The recommended starting dosage is 5 mcg once daily, with a 5 mcg increase every 3 to 4 days until the desired response is achieved. Infants a few months old may require 20 mcg once daily for maintenance. At 1 year of age, 50 mcg once daily may be required. Above 3 years of age, the full adult dosage may be necessary [see Use in Specific Populations (8.4) ]. Newborns (0 to 3 months) at Risk for Cardiac Failure: Consider a lower starting dose in infants at risk for cardiac failure. Increase the dose as needed based on clinical and laboratory response. Pediatric Patients at Risk for Hyperactivity: To minimize the risk of hyperactivity in pediatric patients, start at one-fourth the recommended full replacement dose, and increase on a weekly basis by one-fourth the full recommended replacement dose until the full recommended replacement dose is reached. Pregnancy Pre-existing Hypothyroidism: Thyroid hormone dose requirements may increase during pregnancy. Measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range. For patients with serum TSH above the normal trimester-specific range, increase the dose of thyroid hormone and measure TSH every 4 weeks until a stable dose is reached and serum TSH is within the normal trimester-specific range. Reduce thyroid hormone dosage to pre-pregnancy levels immediately after delivery and measure serum TSH levels 4 to 8 weeks postpartum to ensure thyroid hormone dose is appropriate. 2.3 Recommended Dosage for TSH Suppression in Well-Differentiated Thyroid Cancer The dose of liothyronine sodium should target TSH levels within the desired therapeutic range. This may require higher doses, depending on the target level for TSH suppression. 2.4 Recommended Dosage for Thyroid Suppression Test The recommended dose is 75 mcg to 100 mcg daily for 7 days, with radioactive iodine uptake being determined before and after the 7 day administration of liothyronine sodium. If thyroid function is normal, the radioiodine uptake will drop significantly after treatment. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis. 2.5 Switching from Levothyroxine to Liothyronine Sodium Liothyronine sodium has a rapid onset of action and residual effects of the other thyroid preparation may persist for the first several weeks after initiating liothyronine sodium therapy. When switching a patient to liothyronine sodium, discontinue levothyroxine therapy and initiate liothyronine sodium at a low dosage. Gradually increase the liothyronine sodium dose according to the patient's response. 2.6 Monitoring TSH and Triiodothyronine (T3) Levels Assess the adequacy of therapy by periodic assessment of laboratory tests and clinical evaluation. Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of liothyronine sodium may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors. Adults In adult patients with primary hypothyroidism, monitor serum TSH periodically after initiation of the therapy or any change in dose. To check the immediate response to therapy before the TSH has had a chance to respond or if your patient's status needs to be assessed prior to that point, measurement of total T3 would be most appropriate. In patients on a stable and appropriate replacement dose, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient's clinical status. Pediatrics In pediatric patients with hypothyroidism, assess the adequacy of replacement therapy by measuring serum TSH and T3 levels. For pediatric patients three years of age and older, the recommended monitoring is every 3 to 12 months thereafter, following dose stabilization until growth and puberty are completed. Poor compliance or abnormal values may necessitate more frequent monitoring. Perform routine clinical examination, including assessment of development, mental and physical growth, and bone maturation, at regular intervals. While the general aim of therapy is to normalize the serum TSH level, TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum TSH to decrease below 20 IU per liter after initiation of liothyronine sodium therapy may indicate the child is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of liothyronine sodium [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4) ] . Secondary and Tertiary Hypothyroidism Monitor serum T3 levels and maintain in the normal range.

5 WARNINGS AND PRECAUTIONS • Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate liothyronine sodium 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 liothyronine sodium 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 liothyronine sodium 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 liothyronine sodium therapy. Monitor patients receiving concomitant liothyronine sodium and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiovascular symptoms develop or worsen, reduce or withhold the liothyronine sodium 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 liothyronine sodium [see Contraindications (4) ]. 5.4 Prevention of Hyperthyroidism or Incomplete Treatment of Hypothyroidism Liothyronine sodium has a narrow therapeutic index. Over- or undertreatment with liothyronine sodium 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 liothyronine sodium 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 liothyronine sodium and adjust the dose as necessary [see Drug Interactions (7) and Clinical Pharmacology (12.3) ]. 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 liothyronine sodium [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 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 liothyronine sodium that achieves the desired clinical and biochemical response to mitigate against this risk.

6 ADVERSE REACTIONS Adverse reactions associated with liothyronine sodium therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5.4) 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 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 liothyronine sodium 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 Viatris at 1-877-446-3679 (1-877-4-INFO-RX) 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.