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

Hypothyroidism

Levothyroxine Sodium capsules are indicated as a replacement therapy in adults and pediatric patients 6 years and older with primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

Concurrent use of ketamine and levothyroxine sodium capsules 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 capsules 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 capsules for oral use contain synthetic L-3,3',5,5'-tetraiodothyronine sodium salt [levothyroxine (T ₄) sodium]. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C ₁₅H ₁₀I ₄NNaO ₄ ∙ x H ₂O (where x = 5), molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown:

Levothyroxine Sodium capsules are amber-colored, round/biconvex capsules containing a viscous amber-colored liquid.

The inactive ingredients in Levothyroxine Sodium capsules are gelatin, glycerin and water.

Levothyroxine Sodium capsules are amber-colored, round/biconvex capsules, imprinted with a dosage strength specific letter on one side and containing a viscous amber-colored liquid. They are supplied as follows:

The dosage strength on each box is clearly identified in several locations, and is associated with a distinct color. The color of the circles on the blister is the same color as on the box. Each blister pack contains 10 capsules placed in individual cavities labeled with the dosage strength and the product name (Levothyroxine Sodium capsules).

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.

Levothyroxine Sodium capsules are indicated for use in pediatric patients 6 years and older. The initial dose of Levothyroxine Sodium capsules 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 capsules administration for a trial period. Obtain serum T4 and TSH levels at the end of the trial period, and use laboratory test results and clinical assessments to guide diagnosis and treatment, if warranted.

Because of the increased prevalence of cardiovascular disease among the elderly, initiate Levothyroxine Sodium capsules therapy 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 capsules are contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)].

Adverse reactions associated with Levothyroxine Sodium capsules 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 (GI): 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 capsules ( 7)

Concurrent use of sympathomimetics and levothyroxine sodium capsules 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 capsules are L-thyroxine (T4) indicated for adults and pediatric patients 6 years and older with:

• 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 ( 1)
• Not indicated for treatment of transient hypothyroidism during the recovery phase of subacute thyroiditis ( 1)

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

Levothyroxine sodium capsules 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.

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

Do not separate the individual cavities containing the drug from the intact blister as important information may be lost (i.e., manufacturer/distributor names, distributor contact phone number, lot number, and expiration date), and do not remove the individual capsules from blister packaging until ready to use.

• Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate Levothyroxine Sodium capsules 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 capsules 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 capsules 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 capsules may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on levothyroxine sodium capsules may result in increased levothyroxine sodium capsules requirements.

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

• Administer once daily, 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 an hour of certain foods that may affect Levothyroxine Sodium capsules absorption ( 2.1)
• Swallow Levothyroxine Sodium capsules whole, do not cut, crush, or chew ( 2.1)
• Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food, and the specific nature of the condition being treated. 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 capsules are amber-colored, round/biconvex capsules, imprinted with a dosage strength specific letter on one side and containing a viscous amber-colored liquid and are available as follows:

Pregnancy may require the use of higher doses of Levothyroxine Sodium capsules ( 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 capsules 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 capsules may not be attained for 4 to 6 weeks.

Advise the patient and/or the caregiver to read the FDA-approved patient labeling (Patient Information Sheet).

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 thyroid hormone therapy [see Drug Interactions (7.2)] .

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

Do not separate the individual cavities containing the drug from the intact blister as important information may be lost (i.e., manufacturer/distributor names, distributor contact phone number, lot number, and expiration date), and do not remove the individual capsules from blister packaging until ready to use.

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

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

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

Swallow Levothyroxine Sodium capsules whole, do not cut, crush, or chew.

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 concentrations. 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 capsules may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

• Thyroid hormones, including Levothyroxine Sodium capsules, 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)].

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

Many drugs can exert effects thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to levothyroxine sodium capsules (see Tables 2 to 5 below).

NDC 82347-0005-4

Levothyroxine Sodium Capsules

13 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0010-4

Levothyroxine Sodium Capsules

25 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0015-4

Levothyroxine Sodium Capsules

50 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0020-4

Levothyroxine Sodium Capsules

75 mcg

per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0025-4

Levothyroxine Sodium Capsules

88 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only

YARAL Pharma

3 blisters x 10 capsules

NDC 82347-0030-4

Levothyroxine Sodium Capsules

100 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0035-4

Levothyroxine Sodium Capsules

112 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0040-4

Levothyroxine Sodium Capsules

125 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0045-4

Levothyroxine Sodium Capsules

137 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0050-4

Levothyroxine Sodium Capsules

150 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0055-4

Levothyroxine Sodium Capsules

175 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Parma

NDC 82347-0060-4

Levothyroxine Sodium Capsules

200 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

Thyroid hormone increases metabolic clearance of glucocorticoids. Initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy precipitate an acute adrenal crisis in patient with adrenal insufficiency. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with Levothyroxine Sodium capsules [see Contraindications (4)].

Levothyroxine Sodium capsules have a narrow therapeutic index. Over- or under-treatment with Levothyroxine Sodium capsules 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 Levothyroxine Sodium capsules 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 capsules and adjust the dose as necessary [see Drug Interactions (7) 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 capsules that achieves the desired clinical and biochemical response to mitigate against this risk.

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 Levothyroxine Sodium capsules 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 capsules therapy. Monitor patients receiving concomitant Levothyroxine Sodium capsules and sympathomimetic agents for signs and symptoms of coronary insufficiency . If cardiac symptoms develop or worsen, reduce the Levothyroxine Sodium capsules dose or withhold it for one week and restart at a lower dose.

Hypothyroidism

Levothyroxine Sodium capsules are indicated as a replacement therapy in adults and pediatric patients 6 years and older with primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

Concurrent use of ketamine and levothyroxine sodium capsules 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 capsules 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 capsules for oral use contain synthetic L-3,3',5,5'-tetraiodothyronine sodium salt [levothyroxine (T ₄) sodium]. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C ₁₅H ₁₀I ₄NNaO ₄ ∙ x H ₂O (where x = 5), molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown:

Levothyroxine Sodium capsules are amber-colored, round/biconvex capsules containing a viscous amber-colored liquid.

The inactive ingredients in Levothyroxine Sodium capsules are gelatin, glycerin and water.

Levothyroxine Sodium capsules are amber-colored, round/biconvex capsules, imprinted with a dosage strength specific letter on one side and containing a viscous amber-colored liquid. They are supplied as follows:

The dosage strength on each box is clearly identified in several locations, and is associated with a distinct color. The color of the circles on the blister is the same color as on the box. Each blister pack contains 10 capsules placed in individual cavities labeled with the dosage strength and the product name (Levothyroxine Sodium capsules).

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.

Levothyroxine Sodium capsules are indicated for use in pediatric patients 6 years and older. The initial dose of Levothyroxine Sodium capsules 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 capsules administration for a trial period. Obtain serum T4 and TSH levels at the end of the trial period, and use laboratory test results and clinical assessments to guide diagnosis and treatment, if warranted.

Because of the increased prevalence of cardiovascular disease among the elderly, initiate Levothyroxine Sodium capsules therapy 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 capsules are contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)].

Adverse reactions associated with Levothyroxine Sodium capsules 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 (GI): 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 capsules ( 7)

Concurrent use of sympathomimetics and levothyroxine sodium capsules 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 capsules are L-thyroxine (T4) indicated for adults and pediatric patients 6 years and older with:

• 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 ( 1)
• Not indicated for treatment of transient hypothyroidism during the recovery phase of subacute thyroiditis ( 1)

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

Levothyroxine sodium capsules 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.

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

Do not separate the individual cavities containing the drug from the intact blister as important information may be lost (i.e., manufacturer/distributor names, distributor contact phone number, lot number, and expiration date), and do not remove the individual capsules from blister packaging until ready to use.

• Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate Levothyroxine Sodium capsules 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 capsules 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 capsules 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 capsules may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on levothyroxine sodium capsules may result in increased levothyroxine sodium capsules requirements.

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

• Administer once daily, 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 an hour of certain foods that may affect Levothyroxine Sodium capsules absorption ( 2.1)
• Swallow Levothyroxine Sodium capsules whole, do not cut, crush, or chew ( 2.1)
• Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food, and the specific nature of the condition being treated. 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 capsules are amber-colored, round/biconvex capsules, imprinted with a dosage strength specific letter on one side and containing a viscous amber-colored liquid and are available as follows:

Pregnancy may require the use of higher doses of Levothyroxine Sodium capsules ( 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 capsules 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 capsules may not be attained for 4 to 6 weeks.

Advise the patient and/or the caregiver to read the FDA-approved patient labeling (Patient Information Sheet).

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 thyroid hormone therapy [see Drug Interactions (7.2)] .

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

Do not separate the individual cavities containing the drug from the intact blister as important information may be lost (i.e., manufacturer/distributor names, distributor contact phone number, lot number, and expiration date), and do not remove the individual capsules from blister packaging until ready to use.

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

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

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

Swallow Levothyroxine Sodium capsules whole, do not cut, crush, or chew.

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 concentrations. 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 capsules may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

• Thyroid hormones, including Levothyroxine Sodium capsules, 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)].

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

Many drugs can exert effects thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to levothyroxine sodium capsules (see Tables 2 to 5 below).

NDC 82347-0005-4

Levothyroxine Sodium Capsules

13 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0010-4

Levothyroxine Sodium Capsules

25 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0015-4

Levothyroxine Sodium Capsules

50 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0020-4

Levothyroxine Sodium Capsules

75 mcg

per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0025-4

Levothyroxine Sodium Capsules

88 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only

YARAL Pharma

3 blisters x 10 capsules

NDC 82347-0030-4

Levothyroxine Sodium Capsules

100 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0035-4

Levothyroxine Sodium Capsules

112 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0040-4

Levothyroxine Sodium Capsules

125 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0045-4

Levothyroxine Sodium Capsules

137 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0050-4

Levothyroxine Sodium Capsules

150 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

NDC 82347-0055-4

Levothyroxine Sodium Capsules

175 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Parma

NDC 82347-0060-4

Levothyroxine Sodium Capsules

200 mcg



per capsule

Do not remove individual capsules from blister packaging until ready to use

Swallow capsule whole. Do not cut, crush, or chew.

Rx Only



3 blisters x 10 capsules

YARAL Pharma

Thyroid hormone increases metabolic clearance of glucocorticoids. Initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy precipitate an acute adrenal crisis in patient with adrenal insufficiency. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with Levothyroxine Sodium capsules [see Contraindications (4)].

Levothyroxine Sodium capsules have a narrow therapeutic index. Over- or under-treatment with Levothyroxine Sodium capsules 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 Levothyroxine Sodium capsules 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 capsules and adjust the dose as necessary [see Drug Interactions (7) 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 capsules that achieves the desired clinical and biochemical response to mitigate against this risk.

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 Levothyroxine Sodium capsules 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 capsules therapy. Monitor patients receiving concomitant Levothyroxine Sodium capsules and sympathomimetic agents for signs and symptoms of coronary insufficiency . If cardiac symptoms develop or worsen, reduce the Levothyroxine Sodium capsules dose or withhold it for one week and restart at a lower dose.