These Highlights Do Not Include All The Information Needed To Use Levothyroxine Sodium Tablets Safely And Effectively. See Full Prescribing Information For Levothyroxine Sodium Tablets.

Hypothyroidism

Levothyroxine Sodium Tablets are indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

Storage Conditions

Store at 25°C (77°F); excursions permitted to 15° C to 30° C (59° F to 86° F) [see USP Controlled Room Temperature]. Levothyroxine Sodium Tablets should be protected from light and moisture.

Concurrent use of ketamine and Levothyroxine Sodium Tablets may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients.

The signs and symptoms of overdosage are those of hyperthyroidism [see Warnings and Precautions (5) and Adverse Reactions (6)]. In addition, confusion and disorientation may occur.

Cerebral embolism, shock, coma, and death have been reported. Seizures occurred in a 3-year-old child ingesting 3.6 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.

Reduce the Levothyroxine Sodium Tablets dose or discontinue temporarily if signs or symptoms of overdosage occur. Initiate appropriate supportive treatment as dictated by the patient's medical status.

For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.

Levothyroxine Sodium Tablets contain the active ingredient, levothyroxine, a synthetic crystalline L-3,3',5,5'- tetraiodothyronine in sodium salt form. Synthetic T4 is identical in chemical structure to the T₄ produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C₁₅H₁₀I₄NNaO₄∙xH₂O (where x = 5), molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown:

Levothyroxine Sodium Tablets for oral administration are available in the following strengths: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg, and 300 mcg. Each levothyroxine sodium tablet contains the inactive ingredients butylatedhydroxy toluene, calcium phosphate dibasic dihydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, and color additive(s). Table 6 provides a listing of the color additives by tablet strength:

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.

The initial dose of Levothyroxine Sodium Tablets varies with age and body weight. Dosing adjustments are based on an assessment of the individual patient's clinical and laboratory parameters [see Dosage and Administration (2.3 , 2.4)].

In children in whom a diagnosis of permanent hypothyroidism has not been established, discontinue Levothyroxine Sodium Tablets administration for a trial period, but only after the child is at least 3 years of age. Obtain serum T4 and TSH levels at the end of the trial period, and use laboratory test results and clinical assessment to guide diagnosis and treatment, if warranted.

Because of the increased prevalence of cardiovascular disease among the elderly, initiate Levothyroxine Sodium Tablets at less than the full replacement dose [see Warnings and Precautions (5.1) and Dosage and Administration (2.3)]. Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with levothyroxine overtreatment in the elderly.

Levothyroxine Sodium Tablets are contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)].

Adverse reactions associated with Levothyroxine Sodium Tablets therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5), 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 have been reported rarely with the institution of levothyroxine therapy.

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 Tablets. (7)

Concurrent use of sympathomimetics and Levothyroxine Sodium Tablets may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.

Oral levothyroxine sodium is a synthetic T4 hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present.

Levothyroxine Sodium Tablets are L-thyroxine (T4) indicated 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 increase the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the Levothyroxine Sodium Tablets dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T3) and L-thyroxine (T4) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins.

The physiological actions of thyroid hormones are produced predominantly by T3, the majority of which (approximately 80%) is derived from T4 by deiodination in peripheral tissues.

Addition of Levothyroxine Sodium Tablets therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control, especially when thyroid therapy is started, changed, or discontinued [see Warnings and Precautions (5.5)].

Levothyroxine Sodium Tablets may reduce the therapeutic effects of digitalis glycosides. Serum digitalis glycoside levels may decrease when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.

• •
  Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate Levothyroxine Sodium Tablets 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 Levothyroxine Sodium Tablets 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)

Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and Levothyroxine Sodium Tablets may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk of cardiac arrhythmias and central nervous system stimulation. Levothyroxine Sodium Tablets may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on Levothyroxine Sodium Tablets may result in increased Levothyroxine Sodium Tablets requirements.

Consumption of certain foods may affect Levothyroxine Sodium Tablets absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1)]. Soybean flour, cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of Levothyroxine Sodium Tablets from the gastrointestinal tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability.

• •
  Administer once daily, preferably on an empty stomach, one-half to one hour before breakfast. (2.1)
• •
  Administer at least 4 hours before or after drugs that are known to interfere with absorption. (2.1)
• •
  Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect absorption. (2.1)
• •
  Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, and concomitant medications. Peak therapeutic effect may not be attained for 4-6 weeks. (2.2)
• •
  See full prescribing information for dosing in specific patient populations. (2.3)
• •
  Adequacy of therapy determined with periodic monitoring of TSH and/or T4 as well as clinical status. (2.4)

Levothyroxine Sodium Tablets, in the shape of caplet are available as follows:

Pregnancy may require the use of higher doses of Levothyroxine Sodium Tablets. (2.3, 8.1)

Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. Closely monitor TSH levels in such patients.

The dose of Levothyroxine Sodium Tablets 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 (2.3), 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)].

The peak therapeutic effect of a given dose of Levothyroxine Sodium Tablets may not be attained for 4 to 6 weeks.

NDC 68788-7725

Levothyroxine Sodium Tablets, USP

75 mcg

Rx Only

Inform the patient of the following information to aid in the safe and effective use of Levothyroxine Sodium Tablets:

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 Tablets [see Drug Interactions (7.2)].

Levothyroxine Sodium Tablets, in the shape of caplet are supplied as follows:

Administer Levothyroxine Sodium Tablets as a single daily dose, on an empty stomach, one-half to one hour before breakfast.

Administer Levothyroxine Sodium Tablets at least 4 hours before or after drugs known to interfere with Levothyroxine Sodium Tablets absorption [see Drug Interactions (7.1)].

Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect Levothyroxine Sodium Tablets absorption [see Drug Interactions (7.9) and Clinical Pharmacology (12.3)].

Administer Levothyroxine Sodium Tablets to infants and children who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 mL to 10 mL or 1 teaspoon to 2 teaspoons) of water and immediately administering the suspension by spoon or dropper. Do not store the suspension. Do not administer in foods that decrease absorption of Levothyroxine Sodium Tablets, such as soybean-based infant formula [see Drug Interactions (7.9)].

Consider changes in TBG concentration when interpreting T4 and T3 values. Measure and evaluate unbound (free) hormone and/or determine the free-T4 index (FT4I) in this circumstance. Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentration. Nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens, and corticosteroids decrease TBG concentration. Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

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 Levothyroxine Sodium Tablets may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

Thyroid hormones, including Levothyroxine Sodium Tablets, 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)].

Standard animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of levothyroxine.

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 Tablets (see Tables 2-5 below).

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 Tablets [see Contraindications (4)].

Levothyroxine Sodium Tablets have a narrow therapeutic index. Over- or undertreatment with Levothyroxine Sodium Tablets may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and glucose and lipid metabolism. Titrate the dose of Levothyroxine Sodium Tablets 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 Levothyroxine Sodium Tablets and adjust the dose as necessary [see Drug Interactions (7.9)and Clinical Pharmacology (12.3)].

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 Tablets that achieves the desired clinical and biochemical response to mitigate this risk.

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 Tablets 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 Levothyroxine Sodium Tablets therapy. Monitor patients receiving concomitant Levothyroxine Sodium Tablets and sympathomimetic agents for signs and symptoms of coronary insufficiency.

If cardiac symptoms develop or worsen, reduce the Levothyroxine Sodium Tablets dose or withhold for one week and restart at a lower dose.

Hypothyroidism

Levothyroxine Sodium Tablets are indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

Storage Conditions

Store at 25°C (77°F); excursions permitted to 15° C to 30° C (59° F to 86° F) [see USP Controlled Room Temperature]. Levothyroxine Sodium Tablets should be protected from light and moisture.

Concurrent use of ketamine and Levothyroxine Sodium Tablets may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients.

The signs and symptoms of overdosage are those of hyperthyroidism [see Warnings and Precautions (5) and Adverse Reactions (6)]. In addition, confusion and disorientation may occur.

Cerebral embolism, shock, coma, and death have been reported. Seizures occurred in a 3-year-old child ingesting 3.6 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.

Reduce the Levothyroxine Sodium Tablets dose or discontinue temporarily if signs or symptoms of overdosage occur. Initiate appropriate supportive treatment as dictated by the patient's medical status.

For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.

Levothyroxine Sodium Tablets contain the active ingredient, levothyroxine, a synthetic crystalline L-3,3',5,5'- tetraiodothyronine in sodium salt form. Synthetic T4 is identical in chemical structure to the T₄ produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C₁₅H₁₀I₄NNaO₄∙xH₂O (where x = 5), molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown:

Levothyroxine Sodium Tablets for oral administration are available in the following strengths: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg, and 300 mcg. Each levothyroxine sodium tablet contains the inactive ingredients butylatedhydroxy toluene, calcium phosphate dibasic dihydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, and color additive(s). Table 6 provides a listing of the color additives by tablet strength:

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.

The initial dose of Levothyroxine Sodium Tablets varies with age and body weight. Dosing adjustments are based on an assessment of the individual patient's clinical and laboratory parameters [see Dosage and Administration (2.3 , 2.4)].

In children in whom a diagnosis of permanent hypothyroidism has not been established, discontinue Levothyroxine Sodium Tablets administration for a trial period, but only after the child is at least 3 years of age. Obtain serum T4 and TSH levels at the end of the trial period, and use laboratory test results and clinical assessment to guide diagnosis and treatment, if warranted.

Because of the increased prevalence of cardiovascular disease among the elderly, initiate Levothyroxine Sodium Tablets at less than the full replacement dose [see Warnings and Precautions (5.1) and Dosage and Administration (2.3)]. Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with levothyroxine overtreatment in the elderly.

Levothyroxine Sodium Tablets are contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)].

Adverse reactions associated with Levothyroxine Sodium Tablets therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5), 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 have been reported rarely with the institution of levothyroxine therapy.

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 Tablets. (7)

Concurrent use of sympathomimetics and Levothyroxine Sodium Tablets may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.

Oral levothyroxine sodium is a synthetic T4 hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present.

Levothyroxine Sodium Tablets are L-thyroxine (T4) indicated 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 increase the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the Levothyroxine Sodium Tablets dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T3) and L-thyroxine (T4) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins.

The physiological actions of thyroid hormones are produced predominantly by T3, the majority of which (approximately 80%) is derived from T4 by deiodination in peripheral tissues.

Addition of Levothyroxine Sodium Tablets therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control, especially when thyroid therapy is started, changed, or discontinued [see Warnings and Precautions (5.5)].

Levothyroxine Sodium Tablets may reduce the therapeutic effects of digitalis glycosides. Serum digitalis glycoside levels may decrease when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.

• •
  Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate Levothyroxine Sodium Tablets 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 Levothyroxine Sodium Tablets 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)

Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and Levothyroxine Sodium Tablets may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk of cardiac arrhythmias and central nervous system stimulation. Levothyroxine Sodium Tablets may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on Levothyroxine Sodium Tablets may result in increased Levothyroxine Sodium Tablets requirements.

Consumption of certain foods may affect Levothyroxine Sodium Tablets absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1)]. Soybean flour, cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of Levothyroxine Sodium Tablets from the gastrointestinal tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability.

• •
  Administer once daily, preferably on an empty stomach, one-half to one hour before breakfast. (2.1)
• •
  Administer at least 4 hours before or after drugs that are known to interfere with absorption. (2.1)
• •
  Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect absorption. (2.1)
• •
  Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, and concomitant medications. Peak therapeutic effect may not be attained for 4-6 weeks. (2.2)
• •
  See full prescribing information for dosing in specific patient populations. (2.3)
• •
  Adequacy of therapy determined with periodic monitoring of TSH and/or T4 as well as clinical status. (2.4)

Levothyroxine Sodium Tablets, in the shape of caplet are available as follows:

Pregnancy may require the use of higher doses of Levothyroxine Sodium Tablets. (2.3, 8.1)

Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. Closely monitor TSH levels in such patients.

The dose of Levothyroxine Sodium Tablets 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 (2.3), 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)].

The peak therapeutic effect of a given dose of Levothyroxine Sodium Tablets may not be attained for 4 to 6 weeks.

NDC 68788-7725

Levothyroxine Sodium Tablets, USP

75 mcg

Rx Only

Inform the patient of the following information to aid in the safe and effective use of Levothyroxine Sodium Tablets:

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 Tablets [see Drug Interactions (7.2)].

Levothyroxine Sodium Tablets, in the shape of caplet are supplied as follows:

Administer Levothyroxine Sodium Tablets as a single daily dose, on an empty stomach, one-half to one hour before breakfast.

Administer Levothyroxine Sodium Tablets at least 4 hours before or after drugs known to interfere with Levothyroxine Sodium Tablets absorption [see Drug Interactions (7.1)].

Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect Levothyroxine Sodium Tablets absorption [see Drug Interactions (7.9) and Clinical Pharmacology (12.3)].

Administer Levothyroxine Sodium Tablets to infants and children who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 mL to 10 mL or 1 teaspoon to 2 teaspoons) of water and immediately administering the suspension by spoon or dropper. Do not store the suspension. Do not administer in foods that decrease absorption of Levothyroxine Sodium Tablets, such as soybean-based infant formula [see Drug Interactions (7.9)].

Consider changes in TBG concentration when interpreting T4 and T3 values. Measure and evaluate unbound (free) hormone and/or determine the free-T4 index (FT4I) in this circumstance. Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentration. Nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens, and corticosteroids decrease TBG concentration. Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

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 Levothyroxine Sodium Tablets may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

Thyroid hormones, including Levothyroxine Sodium Tablets, 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)].

Standard animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of levothyroxine.

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 Tablets (see Tables 2-5 below).

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 Tablets [see Contraindications (4)].

Levothyroxine Sodium Tablets have a narrow therapeutic index. Over- or undertreatment with Levothyroxine Sodium Tablets may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and glucose and lipid metabolism. Titrate the dose of Levothyroxine Sodium Tablets 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 Levothyroxine Sodium Tablets and adjust the dose as necessary [see Drug Interactions (7.9)and Clinical Pharmacology (12.3)].

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 Tablets that achieves the desired clinical and biochemical response to mitigate this risk.

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 Tablets 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 Levothyroxine Sodium Tablets therapy. Monitor patients receiving concomitant Levothyroxine Sodium Tablets and sympathomimetic agents for signs and symptoms of coronary insufficiency.

If cardiac symptoms develop or worsen, reduce the Levothyroxine Sodium Tablets dose or withhold for one week and restart at a lower dose.