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

Hypothyroidism

LEVOXYL is indicated in pediatric and adult patients as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

STORAGE CONDITIONS

Store between 68°F–77°F (20°C–25°C) with excursions permitted between 59°F–86°F (15°C–30°C). Store LEVOXYL away from heat, moisture, and light.

Concurrent use of ketamine and LEVOXYL 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 (5.4), 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 LEVOXYL dose or temporarily discontinued 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.

LEVOXYL contains the active ingredient, levothyroxine, asynthetic crystalline levothyroxine (T4) in sodium salt form. It is chemically designated as L-3,3',5,5'-tetraiodothyronine monosodium hydrate. Synthetic T4 is identical in chemical structure to the T4 produced in the human thyroid gland. Levothyroxine sodium has an empirical formula of C₁₅H₁₀I₄N NaO₄ ∙ H₂O, molecular weight of 798.85 g/mol (anhydrous), and structural formula as shown:

LEVOXYL tablets for oral administration are supplied in the following strengths: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, and 200 mcg.

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 LEVOXYL 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 LEVOXYL 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 assessments to guide diagnosis and treatment, if warranted.

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

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

Common adverse reactions with LEVOXYL therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5.4), Overdosage (10)]. They include the following:

General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating

Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia

Musculoskeletal: tremors, muscle weakness and cramps

Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest

Respiratory: dyspnea

Gastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests

Dermatologic: hair loss, flushing

Endocrine: decreased bone mineral density

Reproductive: menstrual irregularities, impaired fertility

Seizures have been reported rarely with 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 LEVOXYL. (7)

Concurrent use of sympathomimetics and LEVOXYL 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.

LEVOXYL is L-thyroxine (T4) indicated in pediatric and adult patients for:

• Hypothyroidism: As replacement 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 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 hypothyroidism during the recovery phase of subacute thyroiditis. (1)

LEVOXYL increases 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 LEVOXYL 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 LEVOXYL 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 LEVOXYL is started, changed, or discontinued [see Warnings and Precautions (5.5)].

LEVOXYL may reduce the therapeutic effects of digitalis glycosides. Serum digitalis glycoside levels may be decreased 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 LEVOXYL 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 LEVOXYL 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 LEVOXYL 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. LEVOXYL may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on LEVOXYL may result in increased LEVOXYL requirements.

Consumption of certain foods may affect LEVOXYL absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1)]. Soybean flour (infant formula), cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of LEVOXYL 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 with a full glass of water. (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, 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 to 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)

LEVOXYL tablets are oval, color-coded and, potency marked available as follows:

Pregnancy may require the use of higher doses of levothyroxine. (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 LEVOXYL 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), 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 LEVOXYL may not be attained for 4 to 6 weeks.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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 LEVOXYL [see Drug Interactions (7.2)].

LEVOXYL (levothyroxine sodium) tablets are oval, color-coded and, potency marked available as follows:

Administer LEVOXYL tablets orally as a single daily dose, on an empty stomach, one-half to one hour before breakfast with a full glass of water to avoid choking or gagging [see Adverse Reactions (6)].

Administer LEVOXYL at least 4 hours before or after drugs that are known to interfere with LEVOXYL absorption [see Drug Interactions (7.1)].

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

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

NDC 60793-850-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

25 mcg

100 Tablets

Rx only

NDC 60793-851-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

50 mcg

100 Tablets

Rx only

NDC 60793-852-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

75 mcg

100 Tablets

Rx only

NDC 60793-853-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

88 mcg

100 Tablets

Rx only

NDC 60793-854-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

100 mcg

100 Tablets

Rx only

NDC 60793-855-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

112 mcg

100 Tablets

Rx only

NDC 60793-856-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

125 mcg

100 Tablets

Rx only

NDC 60793-857-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

137 mcg

100 Tablets

Rx only

NDC 60793-858-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

150 mcg

100 Tablets

Rx only

NDC 60793-859-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

175 mcg

100 Tablets

Rx only

NDC 60793-860-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

200 mcg

100 Tablets

Rx only

• Thyroid hormones, including LEVOXYL, 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), 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 on thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to LEVOXYL (see Tables 2 – 5).

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 LEVOXYL [see Contraindications (4)].

LEVOXYL has a narrow therapeutic index. Over- or undertreatment with LEVOXYL 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 LEVOXYL 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 LEVOXYL and adjust the dose as necessary [see Drug Interactions (7), 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 LEVOXYL 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 LEVOXYL 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 LEVOXYL therapy. Monitor patients receiving concomitant LEVOXYL and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiovascular symptoms develop or worsen, reduce or withhold the LEVOXYL dose for one week and restart at a lower dose.

Hypothyroidism

LEVOXYL is indicated in pediatric and adult patients as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

STORAGE CONDITIONS

Store between 68°F–77°F (20°C–25°C) with excursions permitted between 59°F–86°F (15°C–30°C). Store LEVOXYL away from heat, moisture, and light.

Concurrent use of ketamine and LEVOXYL 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 (5.4), 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 LEVOXYL dose or temporarily discontinued 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.

LEVOXYL contains the active ingredient, levothyroxine, asynthetic crystalline levothyroxine (T4) in sodium salt form. It is chemically designated as L-3,3',5,5'-tetraiodothyronine monosodium hydrate. Synthetic T4 is identical in chemical structure to the T4 produced in the human thyroid gland. Levothyroxine sodium has an empirical formula of C₁₅H₁₀I₄N NaO₄ ∙ H₂O, molecular weight of 798.85 g/mol (anhydrous), and structural formula as shown:

LEVOXYL tablets for oral administration are supplied in the following strengths: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, and 200 mcg.

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 LEVOXYL 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 LEVOXYL 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 assessments to guide diagnosis and treatment, if warranted.

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

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

Common adverse reactions with LEVOXYL therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5.4), Overdosage (10)]. They include the following:

General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating

Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia

Musculoskeletal: tremors, muscle weakness and cramps

Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest

Respiratory: dyspnea

Gastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests

Dermatologic: hair loss, flushing

Endocrine: decreased bone mineral density

Reproductive: menstrual irregularities, impaired fertility

Seizures have been reported rarely with 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 LEVOXYL. (7)

Concurrent use of sympathomimetics and LEVOXYL 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.

LEVOXYL is L-thyroxine (T4) indicated in pediatric and adult patients for:

• Hypothyroidism: As replacement 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 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 hypothyroidism during the recovery phase of subacute thyroiditis. (1)

LEVOXYL increases 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 LEVOXYL 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 LEVOXYL 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 LEVOXYL is started, changed, or discontinued [see Warnings and Precautions (5.5)].

LEVOXYL may reduce the therapeutic effects of digitalis glycosides. Serum digitalis glycoside levels may be decreased 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 LEVOXYL 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 LEVOXYL 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 LEVOXYL 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. LEVOXYL may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on LEVOXYL may result in increased LEVOXYL requirements.

Consumption of certain foods may affect LEVOXYL absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1)]. Soybean flour (infant formula), cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of LEVOXYL 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 with a full glass of water. (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, 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 to 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)

LEVOXYL tablets are oval, color-coded and, potency marked available as follows:

Pregnancy may require the use of higher doses of levothyroxine. (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 LEVOXYL 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), 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 LEVOXYL may not be attained for 4 to 6 weeks.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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 LEVOXYL [see Drug Interactions (7.2)].

LEVOXYL (levothyroxine sodium) tablets are oval, color-coded and, potency marked available as follows:

Administer LEVOXYL tablets orally as a single daily dose, on an empty stomach, one-half to one hour before breakfast with a full glass of water to avoid choking or gagging [see Adverse Reactions (6)].

Administer LEVOXYL at least 4 hours before or after drugs that are known to interfere with LEVOXYL absorption [see Drug Interactions (7.1)].

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

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

NDC 60793-850-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

25 mcg

100 Tablets

Rx only

NDC 60793-851-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

50 mcg

100 Tablets

Rx only

NDC 60793-852-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

75 mcg

100 Tablets

Rx only

NDC 60793-853-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

88 mcg

100 Tablets

Rx only

NDC 60793-854-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

100 mcg

100 Tablets

Rx only

NDC 60793-855-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

112 mcg

100 Tablets

Rx only

NDC 60793-856-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

125 mcg

100 Tablets

Rx only

NDC 60793-857-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

137 mcg

100 Tablets

Rx only

NDC 60793-858-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

150 mcg

100 Tablets

Rx only

NDC 60793-859-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

175 mcg

100 Tablets

Rx only

NDC 60793-860-01

Pfizer

Levoxyl^®

(levothyroxine

sodium tablets, USP)

tablets

200 mcg

100 Tablets

Rx only

• Thyroid hormones, including LEVOXYL, 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), 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 on thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to LEVOXYL (see Tables 2 – 5).

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 LEVOXYL [see Contraindications (4)].

LEVOXYL has a narrow therapeutic index. Over- or undertreatment with LEVOXYL 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 LEVOXYL 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 LEVOXYL and adjust the dose as necessary [see Drug Interactions (7), 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 LEVOXYL 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 LEVOXYL 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 LEVOXYL therapy. Monitor patients receiving concomitant LEVOXYL and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiovascular symptoms develop or worsen, reduce or withhold the LEVOXYL dose for one week and restart at a lower dose.