Levothyroxine: uses, appearance and warnings

Hypothyroidism Levothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression Levothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. Limitations of Use Levothyroxine sodium tablets are 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 levothyroxine sodium tablets may induce hyperthyroidism [see Warnings and Precautions ( 5.1 )]. Levothyroxine sodium tablets are not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis. Levothyroxine sodium tablets are a L-thyroxine (T4) indicated in adult and pediatric patients, including neonates, for: Hypothyroidism: As replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. ( 1 ) Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression: As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. ( 1 ) Limitations of Use: Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients Not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis

Levothyroxine sodium tablets, USP are available as follows (Table 4): Table 4: Levothyroxine Sodium Tablet, USP Strengths and Identifying Features Levothyroxine Sodium Tablets, USP 25 mcg are available as Orange coloured, circular tablets debossed with ‘M56’ on one side and break line on other side. Free from physical defects. Levothyroxine Sodium Tablets, USP 50 mcg are available as White to off white coloured, circular tablets debossed with ‘M57’ on one side and break line on other side. Free from physical defects. Levothyroxine Sodium Tablets, USP 75 mcg are available as Violet coloured, circular tablets debossed with ‘M58’ on one side and break line on other side. Free from physical defects. Levothyroxine Sodium Tablets, USP 88 mcg are available as Olive coloured, circular tablets debossed with ‘M59’ on one side and break line on other side. Free from physical defects. Levothyroxine Sodium Tablets, USP 100 mcg are available as Yellow coloured, circular tablets, debossed with ‘M60’ on one side and break line on the other side. Free from physical defects. Levothyroxine Sodium Tablets, USP 112 mcg are available as Rose coloured, circular tablets debossed with ‘M61’ on one side and break line on other side. Free from physical defects. Levothyroxine Sodium Tablets, USP 125 mcg are available as Brown coloured, circular tablets debossed with ‘M62’ on one side and break line on other side. Free from physical defects. …

How Supplied Levothyroxine sodium tablets, USP are supplied as follows: Levothyroxine Sodium Tablets, USP 25 mcg are available as Orange coloured, circular tablets debossed with ‘M56’ on one side and break line on other side. Bottles of 90 NDC 72603-660-01 Bottles of 1000 NDC 72603-660-02 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-660-11 Levothyroxine Sodium Tablets, USP 50 mcg are available as White to off white coloured, circular tablets debossed with ‘M57’ on one side and break line on other side. Bottles of 90 NDC 72603-661-02 Bottles of 1000 NDC 72603-661-01 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-661-11 Levothyroxine Sodium Tablets, USP 75 mcg are available as Violet coloured, circular tablets debossed with ‘M58’ on one side and break line on other side. Bottles of 90 NDC 72603-662-02 Bottles of 1000 NDC 72603-662-01 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-662-11 Levothyroxine Sodium Tablets, USP 88 mcg are available as Olive coloured, circular tablets debossed with ‘M59’ on one side and break line on other side. Bottles of 90 NDC 72603-663-02 Bottles of 1000 NDC 72603-663-01 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-663-11 Levothyroxine Sodium Tablets, USP 100 mcg are available as Yellow coloured, circular tablets debossed with ‘M60’ on one side and break line on other side. Bottles of 90 NDC 72603-664-01 Bottles of 1000 NDC 72603-664-02 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-664-11 Levothyroxine Sodium Tablets, USP 112 mcg are available as Rose coloured, circular tablets debossed with ‘M61’ on one side and break line on other side. Bottles of 90 NDC 72603-665-02 Bottles of 1000 NDC 72603-665-01 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-665-11 Levothyroxine Sodium Tablets, USP 125 mcg are available as Brown coloured, circular tablets debossed with ‘M62’ on one side and break line on other side. Bottles of 90 NDC 72603-666-02 Bottles of 1000 NDC 72603-666-01 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-666-11 Levothyroxine Sodium Tablets, USP 137 mcg are available as Turquoise coloured, circular tablets debossed with ‘M63’ on one side and break line on other side. Bottles of 90 NDC 72603-667-01 Bottles of 1000 NDC 72603-667-02 Unit dose carton of 100 tablets (10 x 10s) NDC 72603-667-11 Levothyroxine Sodium Tablets, USP 150 mcg are available as Blue coloured, circular tablets debossed with ‘M64’ on one side and break line on other side. …

Levothyroxine sodium tablets are contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions ( 5.4 )]. Uncorrected adrenal insufficiency. ( 4 )

Serious risks related to overtreatment or undertreatment with levothyroxine sodium: Titrate the dose of levothyroxine sodium carefully and monitor response to titration. ( 5.1 ) Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate levothyroxine sodium 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 levothyroxine sodium 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 Levothyroxine Sodium Levothyroxine sodium has a narrow therapeutic index. Overtreatment or undertreatment with levothyroxine sodium 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 levothyroxine sodium 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 levothyroxine sodium as needed [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.1) , and Clinical Pharmacology ( 12.3) ]. 5.2 Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease Over-treatment 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 levothyroxine 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 levothyroxine sodium therapy. Monitor patients receiving concomitant levothyroxine sodium and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiac symptoms develop or worsen, reduce the levothyroxine sodium dose or withhold 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 levothyroxine sodium [ 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 levothyroxine 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 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 levothyroxine sodium that achieves the desired clinical and biochemical response to mitigate this risk.

Adverse reactions associated with levothyroxine sodium 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: 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 …

See full prescribing information for drugs that affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to levothyroxine sodium. ( 7 ) 7.1 Drugs Known to Affect Thyroid Hormone Pharmacokinetics Many drugs can exert effects on thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to levothyroxine sodium (Tables 5 to 8). Table 5. Drugs That May Decrease T4 Absorption (Hypothyroidism) Potential impact: Concurrent use may reduce the efficacy of levothyroxine sodium by binding and delaying or preventing absorption, potentially resulting in hypothyroidism. …