Levothyroxine Sodium for Injection is indicated for the treatment of myxedema coma. Important Limitations of Use: The relative bioavailability between Levothyroxine Sodium for Injection and oral levothyroxine products has not been established. Caution should be used when switching patients from oral levothyroxine products to Levothyroxine Sodium for Injection as accurate dosing conversion has not been studied.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium for Injection is indicated for the treatment of myxedema coma. Important Limitations of Use: The relative bioavailability between Levothyroxine Sodium for Injection and oral levothyroxine products has not been established. Caution should be used when switching patients from oral levothyroxine products to Levothyroxine Sodium for Injection as accurate dosing conversion has not been studied." }

2.1 Dosage

{ "type": "p", "children": [], "text": "\n2.1 Dosage\n" }

An initial intravenous loading dose of Levothyroxine Sodium for Injection between 300 to 500 mcg, followed by once daily intravenous maintenance doses between 50 and 100 mcg, should be administered, as clinically indicated, until the patient can tolerate oral therapy. The age, general physical condition, cardiac risk factors, and clinical severity of myxedema and duration of myxedema symptoms should be considered when determining the starting and maintenance dosages of Levothyroxine Sodium for Injection.

{ "type": "p", "children": [], "text": "An initial intravenous loading dose of Levothyroxine Sodium for Injection between 300 to 500 mcg, followed by once daily intravenous maintenance doses between 50 and 100 mcg, should be administered, as clinically indicated, until the patient can tolerate oral therapy. The age, general physical condition, cardiac risk factors, and clinical severity of myxedema and duration of myxedema symptoms should be considered when determining the starting and maintenance dosages of Levothyroxine Sodium for Injection." }

Levothyroxine Sodium for Injection produces a gradual increase in the circulating concentrations of the hormone with an approximate half-life of 9 to 10 days in hypothyroid patients. Daily administration of Levothyroxine Sodium for Injection should be maintained until the patient is capable of tolerating an oral dose and is clinically stable. For chronic treatment of hypothyroidism, an oral dosage form of levothyroxine should be used to maintain a euthyroid state. Relative bioavailability between Levothyroxine Sodium for Injection and oral levothyroxine products has not been established. Based on medical practice, the relative bioavailability between oral and intravenous administration of Levothyroxine Sodium for Injection is estimated to be from 48 to 74%. Due to differences in absorption characteristics of patients and the oral levothyroxine product formulations, TSH and thyroid hormone levels should be measured a few weeks after initiating oral levothyroxine and dose adjusted accordingly.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium for Injection produces a gradual increase in the circulating concentrations of the hormone with an approximate half-life of 9 to 10 days in hypothyroid patients. Daily administration of Levothyroxine Sodium for Injection should be maintained until the patient is capable of tolerating an oral dose and is clinically stable. For chronic treatment of hypothyroidism, an oral dosage form of levothyroxine should be used to maintain a euthyroid state. Relative bioavailability between Levothyroxine Sodium for Injection and oral levothyroxine products has not been established. Based on medical practice, the relative bioavailability between oral and intravenous administration of Levothyroxine Sodium for Injection is estimated to be from 48 to 74%. Due to differences in absorption characteristics of patients and the oral levothyroxine product formulations, TSH and thyroid hormone levels should be measured a few weeks after initiating oral levothyroxine and dose adjusted accordingly." }

2.2 Dosing in the Elderly and in Patients with Cardiovascular Disease

{ "type": "p", "children": [], "text": "\n2.2 Dosing in the Elderly and in Patients with Cardiovascular Disease\n" }

Intravenous levothyroxine may be associated with cardiac toxicity-including arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death-in the elderly and in those with underlying cardiovascular disease. Therefore, cautious use, including doses in the lower end of the recommended range, may be warranted in these populations.

{ "type": "p", "children": [], "text": "Intravenous levothyroxine may be associated with cardiac toxicity-including arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death-in the elderly and in those with underlying cardiovascular disease. Therefore, cautious use, including doses in the lower end of the recommended range, may be warranted in these populations." }

2.3 Reconstitution Directions

{ "type": "p", "children": [], "text": "\n2.3 Reconstitution Directions\n" }

Reconstitute the lyophilized Levothyroxine Sodium for Injection by aseptically adding 5 mL of 0.9% Sodium Chloride Injection, USP only. Shake vial to ensure complete mixing. The resultant solution will have a final concentration of approximately 20 mcg per mL and 100 mcg per mL for the 100 mcg and 500 mcg vials, respectively. Reconstituted drug product is preservative free and is stable for 4 hours. Discard any unused portion. DO NOT ADD LEVOTHYROXINE SODIUM FOR INJECTION TO OTHER IV FLUIDS. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

{ "type": "p", "children": [], "text": "Reconstitute the lyophilized Levothyroxine Sodium for Injection by aseptically adding 5 mL of 0.9% Sodium Chloride Injection, USP only. Shake vial to ensure complete mixing. The resultant solution will have a final concentration of approximately 20 mcg per mL and 100 mcg per mL for the 100 mcg and 500 mcg vials, respectively. Reconstituted drug product is preservative free and is stable for 4 hours. Discard any unused portion. DO NOT ADD LEVOTHYROXINE SODIUM FOR INJECTION TO OTHER IV FLUIDS. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit." }

Levothyroxine Sodium for Injection is supplied as a lyophilized powder at two strengths in single dose amber-colored vials: 100 mcg and 500 mcg.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium for Injection is supplied as a lyophilized powder at two strengths in single dose amber-colored vials: 100 mcg and 500 mcg." }

None.

{ "type": "p", "children": [], "text": "None." }

5.1 Risk of Cardiac Complications in Elderly and in Patients with Cardiovascular Disease

{ "type": "p", "children": [], "text": "\n5.1 Risk of Cardiac Complications in Elderly and in Patients with Cardiovascular Disease\n" }

Excessive bolus dosing of Levothyroxine Sodium for Injection (greater than 500 mcg) are associated with cardiac complications, particularly in the elderly and in patients with an underlying cardiac condition. Adverse events that can potentially be related to the administration of large doses of Levothyroxine Sodium for Injection include arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death. Cautious use, including doses in the lower end of the recommended range, may be warranted in these populations. Close observation of the patient following the administration of Levothyroxine Sodium for Injection is advised.

{ "type": "p", "children": [], "text": "Excessive bolus dosing of Levothyroxine Sodium for Injection (greater than 500 mcg) are associated with cardiac complications, particularly in the elderly and in patients with an underlying cardiac condition. Adverse events that can potentially be related to the administration of large doses of Levothyroxine Sodium for Injection include arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death. Cautious use, including doses in the lower end of the recommended range, may be warranted in these populations. Close observation of the patient following the administration of Levothyroxine Sodium for Injection is advised." }

5.2 Need for Concomitant Glucocorticoids and Monitoring for Other Diseases in Patients with Endocrine Disorders

{ "type": "p", "children": [], "text": "\n5.2 Need for Concomitant Glucocorticoids and Monitoring for Other Diseases in Patients with Endocrine Disorders\n" }

Occasionally, chronic autoimmune thyroiditis, which can lead to myxedema coma, may occur in association with other autoimmune disorders such as adrenal insufficiency, pernicious anemia, and insulin–dependent diabetes mellitus. Patients should be treated with replacement glucocorticoids prior to initiation of treatment with Levothyroxine Sodium for Injection, until adrenal function has been adequately assessed. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated, due to increased metabolic clearance of glucocorticoids by thyroid hormone. With initiation of Levothyroxine Sodium for Injection, patients with myxedema coma should also be monitored for previously undiagnosed diabetes insipidus.

{ "type": "p", "children": [], "text": "Occasionally, chronic autoimmune thyroiditis, which can lead to myxedema coma, may occur in association with other autoimmune disorders such as adrenal insufficiency, pernicious anemia, and insulin–dependent diabetes mellitus. Patients should be treated with replacement glucocorticoids prior to initiation of treatment with Levothyroxine Sodium for Injection, until adrenal function has been adequately assessed. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated, due to increased metabolic clearance of glucocorticoids by thyroid hormone. With initiation of Levothyroxine Sodium for Injection, patients with myxedema coma should also be monitored for previously undiagnosed diabetes insipidus." }

5.3 Not Indicated for Treatment of Obesity

{ "type": "p", "children": [], "text": "\n5.3 Not Indicated for Treatment of Obesity\n" }

Thyroid hormones, including Levothyroxine Sodium for Injection, 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) and Overdosage (10)].

{ "type": "p", "children": [], "text": "Thyroid hormones, including Levothyroxine Sodium for Injection, 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 [\n See Adverse Reactions (6) and Overdosage (10)].\n " }

Excessive doses of levothyroxine can predispose to signs and symptoms compatible with hyperthyroidism. The signs and symptoms of thyrotoxicosis include, but are not limited to: exophthalmic goiter, weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, angina pectoris, tremors, insomnia, heat intolerance, fever, and menstrual irregularities.

{ "type": "p", "children": [], "text": "Excessive doses of levothyroxine can predispose to signs and symptoms compatible with hyperthyroidism. The signs and symptoms of thyrotoxicosis include, but are not limited to: exophthalmic goiter, weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, angina pectoris, tremors, insomnia, heat intolerance, fever, and menstrual irregularities." }

Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Levothyroxine Sodium for Injection. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs ( See Section12.3).

{ "type": "p", "children": [], "text": "Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Levothyroxine Sodium for Injection. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs (\n See Section12.3).\n " }

7.1 Antidiabetic Therapy

{ "type": "p", "children": [], "text": "\n7.1 Antidiabetic Therapy\n" }

Addition of levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued.

{ "type": "p", "children": [], "text": "Addition of levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued." }

7.2 Oral Anticoagulants

{ "type": "p", "children": [], "text": "\n\n7.2 Oral Anticoagulants\n" }

Levothyroxine 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 Levothyroxine Sodium for Injection dose is increased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments.

{ "type": "p", "children": [], "text": "Levothyroxine 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 Levothyroxine Sodium for Injection dose is increased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments." }

7.3 Digitalis Glycosides The therapeutic effects of digitalis glycosides may be reduced by levothyroxine. Serum digitalis glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.

{ "type": "p", "children": [], "text": "\n\n7.3 Digitalis Glycosides \n\nThe therapeutic effects of digitalis glycosides may be reduced by levothyroxine. Serum digitalis glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.\n " }

7.4 Antidepressant Therapy Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and levothyroxine 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 CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.

{ "type": "p", "children": [], "text": "\n7.4 Antidepressant Therapy \n\nConcurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and levothyroxine 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 CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.\n " }

7.5 Ketamine Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended.

{ "type": "p", "children": [], "text": "\n\n7.5 Ketamine \n\nConcurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended.\n " }

7.6 Sympathomimetics Concurrent use 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.

{ "type": "p", "children": [], "text": "\n\n7.6 Sympathomimetics \n\nConcurrent use 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.\n " }

7.7 Drug-Laboratory Test Interactions Changes in thyroxine binding globulin (TBG) concentration must be considered when interpreting levothyroxine and triiodothyronine values, which necessitates measurement and evaluation of unbound (free) hormone and/or determination of the free levothyroxine index. Pregnancy, infectious hepatitis, estrogens, estrogen containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen or corticosteroid therapy. Familial hyper or hypo thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9,000.

{ "type": "p", "children": [], "text": "\n7.7 Drug-Laboratory Test Interactions \n\nChanges in thyroxine binding globulin (TBG) concentration must be considered when interpreting levothyroxine and triiodothyronine values, which necessitates measurement and evaluation of unbound (free) hormone and/or determination of the free levothyroxine index. Pregnancy, infectious hepatitis, estrogens, estrogen containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen or corticosteroid therapy. Familial hyper or hypo thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9,000.\n " }

8.1 Pregnancy

{ "type": "p", "children": [], "text": "\n8.1 Pregnancy\n" }

Pregnancy Category A – There are no reported cases of Levothyroxine Sodium for Injection used to treat myxedema coma in patients who were pregnant or lactating. Studies in pregnant women treated with oral levothyroxine to maintain a euthyroid state have not shown an increased risk of fetal abnormalities. Therefore, pregnant patients who develop myxedema should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the maternal patient and the fetus.

{ "type": "p", "children": [], "text": "\nPregnancy Category A – There are no reported cases of Levothyroxine Sodium for Injection used to treat myxedema coma in patients who were pregnant or lactating. Studies in pregnant women treated with oral levothyroxine to maintain a euthyroid state have not shown an increased risk of fetal abnormalities. Therefore, pregnant patients who develop myxedema should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the maternal patient and the fetus.\n " }

8.2 Labor and Delivery Patients in labor who develop myxedema have not been reported in the literature. However, patients should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the maternal patient and the fetus.

{ "type": "p", "children": [], "text": "\n\n8.2 Labor and Delivery \n\nPatients in labor who develop myxedema have not been reported in the literature. However, patients should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the maternal patient and the fetus.\n " }

8.3 Nursing Mothers Adequate replacement doses of thyroid hormones are required to maintain normal lactation. There are no reported cases of Levothyroxine Sodium for Injection used to treat myxedema coma in patients who are lactating. However, such patients should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the nursing patient.

{ "type": "p", "children": [], "text": "\n\n8.3 Nursing Mothers \n\nAdequate replacement doses of thyroid hormones are required to maintain normal lactation. There are no reported cases of Levothyroxine Sodium for Injection used to treat myxedema coma in patients who are lactating. However, such patients should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the nursing patient.\n " }

8.4 Pediatric Use Myxedema coma is a disease of the elderly. An approved, oral dosage form of levothyroxine should be used in the pediatric patient population for maintaining a euthyroid state in non-complicated hypothyroidism.

{ "type": "p", "children": [], "text": "\n8.4 Pediatric Use \n\nMyxedema coma is a disease of the elderly. An approved, oral dosage form of levothyroxine should be used in the pediatric patient population for maintaining a euthyroid state in non-complicated hypothyroidism.\n " }

8.5 Geriatric Use and Patients with Underlying Cardiovascular Disease See Section 2, Dosage and Administration, for full prescribing information in the geriatric patient population. Because of the increased prevalence of cardiovascular disease in the elderly, cautious use of Levothyroxine Sodium for Injection in the elderly and in patients with known cardiac risk factors is advised. Atrial fibrillation is a common side effect associated with levothyroxine treatment in the elderly [ See Dosage and Administration (2) and Warnings and Precautions (5)].

{ "type": "p", "children": [], "text": "\n\n8.5 Geriatric Use and Patients with Underlying Cardiovascular Disease \n\nSee Section 2, Dosage and Administration, for full prescribing information in the geriatric patient population. Because of the increased prevalence of cardiovascular disease in the elderly, cautious use of Levothyroxine Sodium for Injection in the elderly and in patients with known cardiac risk factors is advised. Atrial fibrillation is a common side effect associated with levothyroxine treatment in the elderly [ \n See Dosage and Administration (2) and Warnings and Precautions (5)].\n " }

In general, the signs and symptoms of overdosage with levothyroxine 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. Excessive doses of Levothyroxine Sodium for Injection (greater than 500 mcg) are associated with cardiac complications in patients with underlying cardiac disease.

{ "type": "p", "children": [], "text": "In general, the signs and symptoms of overdosage with levothyroxine are those of hyperthyroidism [\n See Warnings and Precautions (\n 5) and \n Adverse Reactions (\n 6)]. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Excessive doses of Levothyroxine Sodium for Injection (greater than 500 mcg) are associated with cardiac complications in patients with underlying cardiac disease.\n " }

Treatment of Overdosage Levothyroxine Sodium for Injection should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient.

{ "type": "p", "children": [], "text": "\nTreatment of Overdosage \n\nLevothyroxine Sodium for Injection should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient.\n " }

In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s medical status.

{ "type": "p", "children": [], "text": "In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s medical status." }

Levothyroxine Sodium for Injection con-tains synthetic crystalline levothyroxine (L-thyroxine) sodium salt.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium for Injection con-tains synthetic crystalline levothyroxine (L-thyroxine) sodium salt. " }

Levothyroxine sodium has an empirical formula of C 15H 10I 4NNaO 4, a molecular weight of 798.85 g/mol (anhydrous), and the following structural formula:

{ "type": "p", "children": [], "text": "Levothyroxine sodium has an empirical formula of C\n 15H\n 10I\n 4NNaO\n 4, a molecular weight of 798.85 g/mol (anhydrous), and the following structural formula:\n " }

Levothyroxine Sodium for Injection is a sterile, preservative-free lyophilized powder consisting of the active ingredient, levothyroxine sodium, and the excipients dibasic sodium phosphate heptahydrate, USP; mannitol, USP; and sodium hydroxide, NF in single-use amber glass vials. Levothyroxine Sodium for Injection is available at two dosage strengths: 100 mcg per vial and 500 mcg per vial.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium for Injection is a sterile, preservative-free lyophilized powder consisting of the active ingredient, levothyroxine sodium, and the excipients dibasic sodium phosphate heptahydrate, USP; mannitol, USP; and sodium hydroxide, NF in single-use amber glass vials. Levothyroxine Sodium for Injection is available at two dosage strengths: 100 mcg per vial and 500 mcg per vial." }

12.1 Mechanism of Action

{ "type": "p", "children": [], "text": "\n12.1 Mechanism of Action\n" }

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T 3) and levothyroxine (T 4) 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.

{ "type": "p", "children": [], "text": "Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T\n 3) and levothyroxine (T\n 4) 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.\n " }

The physiological actions of thyroid hormones are produced predominantly by T 3, the majority of which (approximately 80%) is derived from T 4 by deiodination in peripheral tissues.

{ "type": "p", "children": [], "text": "The physiological actions of thyroid hormones are produced predominantly by T\n 3, the majority of which (approximately 80%) is derived from T\n 4 by deiodination in peripheral tissues.\n " }

12.2 Pharmacodynamics

{ "type": "p", "children": [], "text": "\n12.2 Pharmacodynamics\n" }

Thyroid hormone synthesis and secretion is regulated by the hypothalamic pituitary-thyroid axis. Thyrotropin releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyrotropin stimulating hormone (TSH) from the anterior pituitary. TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, T 4 and T 3, by the thyroid gland. Circulating serum T 3 and T 4 levels exert a feedback effect on both TRH and TSH secretion. When serum T 3 and T 4 levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increases. TSH is used for the diagnosis of hypothyroidism and evaluation of levothyroxine therapy adequacy with other laboratory and clinical data. [See Dosage ( 2.1)] There are drugs known to affect thyroid hormones and TSH by various mechanisms and those examples are diazepam, ethioamide, lovastatin, metoclopramide, 6-mercaptopurine, nitroprusside, perphenazine, and thiazide diuretics. Some drugs may cause a transient decrease in TSH secretion without hypothyroidism and those drugs (dose) are dopamine (greater than 1 mcg per kg per min), glucocorticoids (hydrocortisone greater than 100 mg per day or equivalent) and octreotide (greater than 100 mcg per day).

{ "type": "p", "children": [], "text": "Thyroid hormone synthesis and secretion is regulated by the hypothalamic pituitary-thyroid axis. Thyrotropin releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyrotropin stimulating hormone (TSH) from the anterior pituitary. TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, T\n 4 and T\n 3, by the thyroid gland. Circulating serum T\n 3 and T\n 4 levels exert a feedback effect on both TRH and TSH secretion. When serum T\n 3 and T\n 4 levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increases. TSH is used for the diagnosis of hypothyroidism and evaluation of levothyroxine therapy adequacy with other laboratory and clinical data. \n [See Dosage (\n 2.1)]\n There are drugs known to affect thyroid hormones and TSH by various mechanisms and those examples are diazepam, ethioamide, lovastatin, metoclopramide, 6-mercaptopurine, nitroprusside, perphenazine, and thiazide diuretics. Some drugs may cause a transient decrease in TSH secretion without hypothyroidism and those drugs (dose) are dopamine (greater than 1 mcg per kg per min), glucocorticoids (hydrocortisone greater than 100 mg per day or equivalent) and octreotide (greater than 100 mcg per day).\n " }

Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal maturation of the central nervous system and bone. The metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. The protein anabolic effects of thyroid hormones are essential to normal growth and development.

{ "type": "p", "children": [], "text": "Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal maturation of the central nervous system and bone. The metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. The protein anabolic effects of thyroid hormones are essential to normal growth and development." }

12.3 Pharmacokinetics

{ "type": "p", "children": [], "text": "\n12.3 Pharmacokinetics\n" }

Absorption – Levothyroxine Sodium for Injection is administered via the intravenous route. Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously.

{ "type": "p", "children": [], "text": "\nAbsorption – Levothyroxine Sodium for Injection is administered via the intravenous route. Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously.\n " }

Distribution – Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T 4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T 4 compared to T 3. Protein bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [ See Warnings and Precautions ( 5) and Drug Interactions ( 7)]. Thyroid hormones do not readily cross the placental barrier [ See Warnings and Precautions ( 5) and Use in Specific Populations ( 8)].

{ "type": "p", "children": [], "text": "\nDistribution – Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T\n 4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T\n 4 compared to T\n 3. Protein bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [\n See Warnings and Precautions (\n 5) and \n Drug Interactions (\n 7)]. Thyroid hormones do not readily cross the placental barrier [\n See Warnings and Precautions (\n 5) and \n Use in Specific Populations (\n 8)].\n " }

Metabolism – T 4 is slowly eliminated. The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately eighty percent of circulating T 3 is derived from peripheral T 4 by monodeiodination. The liver is the major site of degradation for both T 4 and T 3, with T 4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T 4 is deiodinated to yield equal amounts of T 3 and reverse T 3 (r T 3). T 3 and r T 3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.

{ "type": "p", "children": [], "text": "\nMetabolism – T\n 4 is slowly eliminated. The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately eighty percent of circulating T\n 3 is derived from peripheral T\n 4 by monodeiodination. The liver is the major site of degradation for both T\n 4 and T\n 3, with T\n 4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T\n 4 is deiodinated to yield equal amounts of T\n 3 and reverse T\n 3 (r T\n 3). T\n 3 and r T\n 3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.\n " }

Elimination – Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged, where it is hydrolyzed and eliminated in feces as the free hormones. Urinary excretion of T 4 decreases with age.

{ "type": "p", "children": [], "text": "\n\nElimination – Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged, where it is hydrolyzed and eliminated in feces as the free hormones. Urinary excretion of T\n 4 decreases with age.\n " }

Table 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients

{ "type": "p", "children": [], "text": "\nTable 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients\n " }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">Hormone</span> </p> </td><td> <p class="First"> <span class="Bold">Ratio in Thyroglobulin</span> </p> </td><td> <p class="First"> <span class="Bold">Biologic Potency</span> </p> </td><td> <p class="First"> <span class="Bold">Half-Life (Days)</span> </p> </td><td> <p class="First"> <span class="Bold">Protein Binding (%) <span class="Sup">2</span></span> </p> </td> </tr> <tr> <td> <p class="First">T <span class="Sub">4</span> </p> </td><td> <p class="First">10 - 20</p> </td><td> <p class="First">1</p> </td><td> <p class="First">6 - 8 <span class="Sup">1</span> </p> </td><td> <p class="First">99.96</p> </td> </tr> <tr class="Last"> <td> <p class="First">T <span class="Sub">3</span> </p> </td><td> <p class="First">1</p> </td><td> <p class="First">4</p> </td><td> <p class="First">≤ 2</p> </td><td> <p class="First">99.5</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">Hormone</span>\n</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\">Ratio in Thyroglobulin</span>\n</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\">Biologic Potency</span>\n</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\">Half-Life (Days)</span>\n</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\">Protein Binding (%)\n <span class=\"Sup\">2</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">T\n <span class=\"Sub\">4</span>\n</p>\n</td><td>\n<p class=\"First\">10 - 20</p>\n</td><td>\n<p class=\"First\">1</p>\n</td><td>\n<p class=\"First\">6 - 8\n <span class=\"Sup\">1</span>\n</p>\n</td><td>\n<p class=\"First\">99.96</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>\n<p class=\"First\">T\n <span class=\"Sub\">3</span>\n</p>\n</td><td>\n<p class=\"First\">1</p>\n</td><td>\n<p class=\"First\">4</p>\n</td><td>\n<p class=\"First\">≤ 2</p>\n</td><td>\n<p class=\"First\">99.5</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

T 4: Levothyroxine

{ "type": "p", "children": [], "text": "T\n 4: Levothyroxine\n " }

T 3: Liothyronine

{ "type": "p", "children": [], "text": "T\n 3: Liothyronine\n " }

1 3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism

{ "type": "p", "children": [], "text": "\n1 3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism\n " }

2 Includes TBG, TBPA, and TBA.

{ "type": "p", "children": [], "text": "\n2 Includes TBG, TBPA, and TBA.\n " }

Drug Interactions

{ "type": "p", "children": [], "text": "\nDrug Interactions\n" }

A listing of drug interaction with T 4 is provided in the following tables, although it may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.

{ "type": "p", "children": [], "text": "A listing of drug interaction with T\n 4 is provided in the following tables, although it may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.\n " }

Table 2: Drugs That May Alter T 4 and T 3 Serum Transport Without Affecting free T 4 Concentration (Euthyroidism)

{ "type": "p", "children": [], "text": "\nTable 2: Drugs That May Alter T\n 4 and T\n 3 Serum Transport Without Affecting free T\n 4 Concentration (Euthyroidism)\n " }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="658px"> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">Drugs That May Increase Serum TBG Concentration</span> </p> </td><td> <p class="First"> <span class="Bold">Drugs That May Decrease Serum TBG Concentration</span> </p> </td> </tr> <tr> <td> <p class="First">Clofibrate Estrogen-containing oral contraceptives</p> <p>Estrogens (oral) Heroin/ Methadone 5-Fluorouracil</p> <p>Mitotane</p> <p>Tamoxifen</p> </td><td> <p class="First">Androgens / Anabolic Steroids</p> <p>Asparaginase</p> <p>Glucocorticoids</p> <p>Slow-Release Nicotinic Acid</p> </td> </tr> <tr> <td colspan="2"> <p class="First"> <span class="Bold">Drugs That May Cause Protein-Binding Site Displacement</span> </p> <p>Potential impact: Administration of these agents with levothyroxine results in an initial transient increase in FT <span class="Sub">4</span>. Continued administration results in a decrease in serum T <span class="Sub">4</span> and normal FT <span class="Sub">4</span> and TSH concentrations and, therefore, patients are clinically euthyroid. </p> </td> </tr> <tr> <td> <p class="First">Salicylates (&gt; 2g/day)</p> </td><td> <p class="First">Salicylates inhibit binding of T <span class="Sub">4</span> and T <span class="Sub">3</span> to TBG and transthyretin. An initial increase in serum FT <span class="Sub">4</span> is followed by return of FT <span class="Sub">4</span> to normal levels with sustained therapeutic serum salicylate concentrations, although total-T <span class="Sub">4</span> levels may decrease by as much as 30%. </p> </td> </tr> <tr class="Last"> <td> <p class="First">Other drugs: Furosemide (&gt;80 mg IV)</p> <p>Heparin Hydantoins Non-Steroidal Anti-inflammatory Drugs</p> <p>- Fenamates</p> <p>- Phenylbutazone</p> </td><td></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"658px\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">Drugs That May Increase Serum TBG Concentration</span>\n</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\">Drugs That May Decrease Serum TBG Concentration</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">Clofibrate Estrogen-containing oral contraceptives</p>\n<p>Estrogens (oral) Heroin/ Methadone 5-Fluorouracil</p>\n<p>Mitotane</p>\n<p>Tamoxifen</p>\n</td><td>\n<p class=\"First\">Androgens / Anabolic Steroids</p>\n<p>Asparaginase</p>\n<p>Glucocorticoids</p>\n<p>Slow-Release Nicotinic Acid</p>\n</td>\n</tr>\n<tr>\n<td colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Drugs That May Cause Protein-Binding Site Displacement</span>\n</p>\n<p>Potential impact: Administration of these agents with levothyroxine results in an initial transient increase in FT\n <span class=\"Sub\">4</span>. Continued administration results in a decrease in serum T\n <span class=\"Sub\">4</span> and normal FT\n <span class=\"Sub\">4</span> and TSH concentrations and, therefore, patients are clinically euthyroid.\n </p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">Salicylates (&gt; 2g/day)</p>\n</td><td>\n<p class=\"First\">Salicylates inhibit binding of T\n <span class=\"Sub\">4</span> and T\n <span class=\"Sub\">3</span> to TBG and transthyretin. An initial increase in serum FT\n <span class=\"Sub\">4</span> is followed by return of FT\n <span class=\"Sub\">4</span> to normal levels with sustained therapeutic serum salicylate concentrations, although total-T\n <span class=\"Sub\">4</span> levels may decrease by as much as 30%.\n </p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>\n<p class=\"First\">Other drugs: Furosemide (&gt;80 mg IV)</p>\n<p>Heparin Hydantoins Non-Steroidal Anti-inflammatory Drugs</p>\n<p>- Fenamates</p>\n<p>- Phenylbutazone</p>\n</td><td></td>\n</tr>\n</tbody>\n</table></div>" }

Table 3: Drugs That May Alter Hepatic Metabolism of T 4 (Hypothyroidism)

{ "type": "p", "children": [], "text": "\nTable 3: Drugs That May Alter Hepatic Metabolism of T\n 4 (Hypothyroidism)\n " }

Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increase levothyroxine requirements.

{ "type": "p", "children": [], "text": "Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increase levothyroxine requirements." }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="674px"> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td></td> </tr> <tr> <td> <p class="First">Carbamazepine</p> <p>Hydantoins</p> </td><td> <p class="First">Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total- and free-T <span class="Sub">4</span> may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. </p> </td> </tr> <tr class="Last"> <td> <p class="First">Other drugs:</p> <p>Phenobarbital</p> <p>Rifampin</p> </td><td></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"674px\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">Drug or Drug Class</span>\n</p>\n</td><td></td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">Carbamazepine</p>\n<p>Hydantoins</p>\n</td><td>\n<p class=\"First\">Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total- and free-T\n <span class=\"Sub\">4</span> may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid.\n </p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>\n<p class=\"First\">Other drugs:</p>\n<p>Phenobarbital</p>\n<p>Rifampin</p>\n</td><td></td>\n</tr>\n</tbody>\n</table></div>" }

Table 4: Drugs That May Decrease Conversion of T 4 to T 3

{ "type": "p", "children": [], "text": "\nTable 4: Drugs That May Decrease Conversion of T\n 4 to T\n 3\n" }

Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T 4 to T 3, leading to decreased T 3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased.

{ "type": "p", "children": [], "text": "Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T\n 4 to T\n 3, leading to decreased T\n 3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased.\n " }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="670px"> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr> <td> <p class="First">Beta-adrenergic antagonists</p> <p>(e.g. Propranolol &gt; 160 mg/day)</p> </td><td> <p class="First">In patients treated with large doses of propranolol (&gt; 160 mg/day), T3 and T4 levels change slightly, TSH levels remain normal, and patients are clinically euthyroid. It should be noted that actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state.</p> </td> </tr> <tr> <td> <p class="First">Glucocorticoids</p> <p>(e.g. Dexamethasone ≥ 4 mg/day)</p> </td><td> <p class="First">Short-term administration of large doses of glucocorticoids may decrease serum T <span class="Sub">3</span> concentrations by 30% with minimal change in serum T <span class="Sub">4</span> levels. However, long-term glucocorticoid therapy may result in slightly decreased T <span class="Sub">3</span> and T <span class="Sub">4</span> levels due to decreased TBG production (See above). </p> </td> </tr> <tr class="Last"> <td> <p class="First">Other drug: Amiodarone</p> </td><td></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"670px\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">Drug or Drug Class</span>\n</p>\n</td><td>\n<p class=\"First\">\n<span class=\"Bold\">Effect</span>\n</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">Beta-adrenergic antagonists</p>\n<p>(e.g. Propranolol &gt; 160 mg/day)</p>\n</td><td>\n<p class=\"First\">In patients treated with large doses of propranolol (&gt; 160 mg/day), T3 and T4 levels change slightly, TSH levels remain normal, and patients are clinically euthyroid. It should be noted that actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state.</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">Glucocorticoids</p>\n<p>(e.g. Dexamethasone ≥ 4 mg/day)</p>\n</td><td>\n<p class=\"First\">Short-term administration of large doses of glucocorticoids may decrease serum T\n <span class=\"Sub\">3</span> concentrations by 30% with minimal change in serum T\n <span class=\"Sub\">4</span> levels. However, long-term glucocorticoid therapy may result in slightly decreased T\n <span class=\"Sub\">3</span> and T\n <span class=\"Sub\">4</span> levels due to decreased TBG production (See above).\n </p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>\n<p class=\"First\">Other drug: Amiodarone</p>\n</td><td></td>\n</tr>\n</tbody>\n</table></div>" }

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

{ "type": "p", "children": [], "text": "\n13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility\n" }

Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of Levothyroxine Sodium for Injection.

{ "type": "p", "children": [], "text": "Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of Levothyroxine Sodium for Injection." }

13.2 Animal Toxicology and Pharmacology No animal toxicology studies have been conducted with Levothyroxine Sodium for Injection.

{ "type": "p", "children": [], "text": "\n\n13.2 Animal Toxicology and Pharmacology \n\nNo animal toxicology studies have been conducted with Levothyroxine Sodium for Injection.\n " }

No clinical studies have been conducted with Levothyroxine Sodium for Injection in patients with myxedema coma. However, data from published literature support the intravenous use of levothyroxine sodium for the treatment of myxedema coma.

{ "type": "p", "children": [], "text": "No clinical studies have been conducted with Levothyroxine Sodium for Injection in patients with myxedema coma. However, data from published literature support the intravenous use of levothyroxine sodium for the treatment of myxedema coma." }

16.1 How Supplied

{ "type": "p", "children": [], "text": "\n16.1 How Supplied\n" }

Levothyroxine Sodium for Injection is available in two dosage strengths.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium for Injection is available in two dosage strengths." }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="First"> <td> <p class="First">Strength</p> </td><td> <p class="First">Reconstitution Concentration</p> </td><td> <p class="First">NDC No.</p> </td> </tr> <tr> <td> <p class="First">100 mcg/vial</p> </td><td> <p class="First">20 mcg/mL</p> </td><td> <p class="First">66794-200-02</p> </td> </tr> <tr class="Last"> <td> <p class="First">500 mcg/vial</p> </td><td> <p class="First">100 mcg/mL</p> </td><td> <p class="First">66794-201-02</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">Strength</p>\n</td><td>\n<p class=\"First\">Reconstitution Concentration</p>\n</td><td>\n<p class=\"First\">NDC No.</p>\n</td>\n</tr>\n<tr>\n<td>\n<p class=\"First\">100 mcg/vial</p>\n</td><td>\n<p class=\"First\">20 mcg/mL</p>\n</td><td>\n<p class=\"First\">66794-200-02</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>\n<p class=\"First\">500 mcg/vial</p>\n</td><td>\n<p class=\"First\">100 mcg/mL</p>\n</td><td>\n<p class=\"First\">66794-201-02</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

16.2 Storage and Handling

{ "type": "p", "children": [], "text": "\n16.2 Storage and Handling\n" }

Protect from light and store dry product at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Reconstituted drug product is preservative free. Discard any unused portion.

{ "type": "p", "children": [], "text": "Protect from light and store dry product at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Reconstituted drug product is preservative free. Discard any unused portion." }

This container closure is not made with natural rubber latex.

{ "type": "p", "children": [], "text": "This container closure is not made with natural rubber latex." }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Piramal Critical Care, Inc.

{ "type": "p", "children": [], "text": "Piramal Critical Care, Inc." }

Bethlehem, PA 18017, USA

{ "type": "p", "children": [], "text": "Bethlehem, PA 18017, USA" }

Issued: 05/2022

{ "type": "p", "children": [], "text": "Issued: 05/2022" }

Levothyroxine Sodium - 100mcg/vial

{ "type": "p", "children": [], "text": "Levothyroxine Sodium - 100mcg/vial" }

NDC - 66794-200-02

{ "type": "p", "children": [], "text": "NDC - 66794-200-02" }

Vial Label

{ "type": "p", "children": [], "text": "Vial Label" }

Carton Label

{ "type": "p", "children": [], "text": "Carton Label" }

Levothyroxine Sodium - 100mcg/vial

{ "type": "p", "children": [], "text": "Levothyroxine Sodium - 100mcg/vial" }

NDC - 66794-201-02

{ "type": "p", "children": [], "text": "NDC - 66794-201-02" }

Vial Label

{ "type": "p", "children": [], "text": "Vial Label" }

Carton Label

{ "type": "p", "children": [], "text": "Carton Label" }

Levothyroxine Sodium Injection is indicated for the treatment of myxedema coma.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium Injection is indicated for the treatment of myxedema coma." }

Limitations of Use: The relative bioavailability between Levothyroxine Sodium Injection and oral levothyroxine products has not been established.  Caution should be used when switching patients from oral levothyroxine products to Levothyroxine Sodium Injection as accurate dosing conversion has not been studied.

{ "type": "p", "children": [], "text": "\nLimitations of Use: The relative bioavailability between Levothyroxine Sodium Injection and oral levothyroxine products has not been established.  Caution should be used when switching patients from oral levothyroxine products to Levothyroxine Sodium Injection as accurate dosing conversion has not been studied." }

An initial intravenous loading dose of Levothyroxine Sodium Injection between 300 to 500 mcg, followed by once daily intravenous maintenance doses between 50 and 100 mcg, should be administered, as clinically indicated, until the patient can tolerate oral therapy. 

The age, general physical condition, and cardiac risk factors of the patient, as well as the clinical severity of myxedema and duration of myxedema symptoms should be considered when determining the starting and maintenance dosages of Levothyroxine Sodium Injection.

Levothyroxine Sodium Injection produces a gradual increase in the circulating concentrations of the hormone with an approximate half-life of 9 to 10 days in hypothyroid patients.  Daily administration of Levothyroxine Sodium Injection should be maintained until the patient is capable of tolerating an oral dose and is clinically stable.  For chronic treatment of hypothyroidism, an oral dosage form of levothyroxine should be used to maintain a euthyroid state.  Relative bioavailability between Levothyroxine Sodium Injection and oral levothyroxine products has not been established.  Based on medical practice, the relative bioavailability between oral and intravenous administration of Levothyroxine Sodium Injection is estimated to be from 48 to 74%.  Due to differences in absorption characteristics of patients and the oral levothyroxine product formulations, TSH and thyroid hormone levels should be measured a few weeks after initiating oral levothyroxine and dose adjusted accordingly.

Intravenous levothyroxine may be associated with cardiac toxicity – including arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death – in the elderly and in those with underlying cardiovascular disease. Therefore, cautious use, including doses in the lower end of the recommended range, may be warranted in these populations.

Intravenous levothyroxine may be associated with cardiac toxicity-including arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death—in the elderly and in those with underlying cardiovascular disease. Therefore, cautious use, including doses in the lower end of the recommended range, may be warranted in these populations.

Discard any unused portion. DO NOT ADD LEVOTHYROXINE SODIUM INJECTION TO OTHER INTRAVENOUS FLUIDS. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Levothyroxine sodium injection 100 mcg/mL is a clear, colorless to slightly yellow solution supplied as 1 mL per vial.

{ "type": "p", "children": [], "text": "Levothyroxine sodium injection 100 mcg/mL is a clear, colorless to slightly yellow solution supplied as 1 mL per vial." }

None

{ "type": "p", "children": [], "text": "None" }

Excessive bolus dosing of Levothyroxine Sodium Injection (greater than 500 mcg) is associated with cardiac complications, particularly in the elderly and in patients with an underlying cardiac condition.  Adverse events that can potentially be related to the administration of large doses of Levothyroxine Sodium Injection include arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death.  Cautious use, including doses in the lower end of the recommended range, may be warranted in these populations.  Close observation of the patient following the administration of Levothyroxine Sodium Injection is advised.

Chronic autoimmune thyroiditis, which can lead to myxedema coma, may occur in association with other autoimmune disorders such as adrenal insufficiency, pernicious anemia, and insulin‑dependent diabetes mellitus. Patients should be treated with replacement glucocorticoids prior to initiation of treatment with Levothyroxine Sodium Injection, until adrenal function has been adequately assessed.  Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated, due to increased metabolic clearance of glucocorticoids by thyroid hormone.  With initiation of Levothyroxine Sodium Injection, patients with myxedema coma should also be monitored for previously undiagnosed diabetes insipidus.

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 [see Drug Interactions (7.1)].

Adverse reactions associated with levothyroxine are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5), Overdosage (10)]. They include the following:

{ "type": "p", "children": [], "text": "Adverse reactions associated with levothyroxine are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5), Overdosage (10)]. They include the following:" }

{ "type": "ul", "children": [ "\nGeneral: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating", "\nCentral nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia", "\nMusculoskeletal: tremors, muscle weakness, muscle spasm", "\nCardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest", "\nRespiratory: dyspnea", "\nGastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests", "\nDermatologic: flushing, rash" ], "text": "" }

Seizures have been reported rarely with the institution of levothyroxine therapy.

{ "type": "p", "children": [], "text": "Seizures have been reported rarely with the institution of levothyroxine therapy." }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\n" }

Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

{ "type": "p", "children": [], "text": "Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur." }

Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Levothyroxine Sodium Injection (see Tables 1-3).

<div class="scrollingtable"><table> <caption> <span>Table 1: Drugs That May Alter T<span class="Sub">4</span> and Triiodothyronine (T<span class="Sub">3</span>) Serum Transport Without Effecting Free Thyroxine (FT<span class="Sub">4</span>) Concentration (Euthyroidism)</span> </caption> <col width="50%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td align="center" class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clofibrate</p> <p>Estrogen-containing oral contraceptives</p> <p>Estrogens (oral)</p> <p>Heroin/Methadone</p> <p>5-Fluorouracil</p> <p>Mitotane</p> <p>Tamoxifen</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">These drugs may increase serum thyroxine-binding globulin (TBG) concentration.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Androgens/Anabolic Steroids</p> <p>Asparaginase</p> <p>Glucocorticoids</p> <p>Slow-Release Nictonic Acid</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">These drugs may decrease serum TBG concentration.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Potential impact (below): Administration of these agents with levothyroxine results in an initial transient increase in FT<span class="Sub">4</span>. Continued administration results in a decrease in serum T<span class="Sub">4</span> and normal FT<span class="Sub">4</span> and TSH concentrations.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Salicylates (&gt; 2 g/day)<br/> <br/> <br/> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Salicylates inhibit binding of T<span class="Sub">4</span> and T<span class="Sub">3</span> to TBG and transthyretin. An initial increase in serum FT<span class="Sub">4</span> is followed by return of FT<span class="Sub">4</span> to normal levels with sustained therapeutic serum salicylate concentrations, although total T<span class="Sub">4</span> levels may decrease by as much as 30%.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Other drugs:</p> <p>Carbamazepine</p> <p>Furosemide (&gt; 80 mg IV)</p> <p>Heparin</p> <p>Hydantoins</p> <p>Non-Steroidal Anti-Inflammatory Drugs</p> <p>-    Fenamates</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">These drugs may cause protein-binding site displacement. Furosemide has been shown to inhibit the protein binding of T4 to TBG and albumin, causing an increase free T4 fraction in serum. Furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower the total T4 level. Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total and free T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Closely monitor thyroid hormone parameters.</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table> <caption> <span>Table 2: Drugs That May Alter Hepatic Metabolism of T<span class="Sub">4</span> (Hypothyroidism)</span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First">Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements.</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Phenobarbital<br/>Rifampin</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Phenobarbital has been shown to reduce the response to thyroxine. Phenobarbital increases L-thyroxine metabolism by inducing uridine 5’-diphospho-glucuronosyltransferase (UGT) and leads to a lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Rifampin has been shown to accelerate the metabolism of levothyroxine. </p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table> <caption> <span>Table 3: Drugs That May Decrease Conversion of T<span class="Sub">4</span> to T<span class="Sub">3</span></span> </caption> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T<span class="Sub">4</span> to T<span class="Sub">3</span>, leading to decreased T<span class="Sub">3</span> levels. However, serum T<span class="Sub">4</span> levels are usually normal but may occasionally be slightly increased.</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td align="center" class="Botrule Rrule"> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Beta-adrenergic antagonists</p> <p>e.g., Propranolol &gt; 160 mg/day)<br/> <br/> <br/> </p> </td><td class="Botrule Rrule"> <p class="First">In patients treated with large doses of propranolol (&gt; 160 mg/day), T<span class="Sub">3</span> and T<span class="Sub">4</span> levels change slightly, TSH levels remain normal, and patients are clinically euthyroid. It should be noted that actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Glucocorticoids<br/>(e.g., Dexamethasone ≥ 4 mg/day)</p> </td><td class="Botrule Rrule"> <p class="First">Short-term administration of large doses of glucocorticoids may decrease serum T<span class="Sub">3</span> concentrations by 30% with minimal change in serum T<span class="Sub">4</span> levels. However, long-term glucocorticoid therapy may result in slightly decreased T<span class="Sub">3</span> and T<span class="Sub">4</span> levels due to decreased TBG production (See above).</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Other drugs:<br/>Amiodarone</p> </td><td class="Botrule Rrule"> <p class="First">Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, and decreased or normal free-T3) in clinically euthyroid patients.</p> </td> </tr> </tbody> </table></div>

Addition of levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements.  Careful monitoring of diabetic control is recommended.

Levothyroxine increases the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

Levothyroxine 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.

Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and levothyroxine 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 may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.

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

Concurrent use may of sympathomimetics and levothyroxine 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.

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.

Risk Summary

The clinical data in pregnant women treated with oral levothyroxine to treat hypothyroidism do not indicate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no data available on the use of Levothyroxine Sodium Injection in pregnant women. There are risks to the mother and fetus associated with myxedema coma in pregnancy (see Clinical Considerations).

No developmental or reproductive toxicity studies in animals have been conducted with Levothyroxine Sodium Injection.

The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have background risks of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Myxedema coma is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with myxedema coma increases the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for pregnant women with myxedema coma should not be withheld due to potential concerns regarding the effects of Levothyroxine Sodium Injection on the fetus.

Risk Summary

Published studies report that levothyroxine is present in human milk following the administration of oral levothyroxine. No adverse effects on the breastfed infant have been reported, and there is no information on the effects of levothyroxine on milk production from levothyroxine oral treatment. There are no available data with use of Levothyroxine Sodium Injection in lactating women. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Levothyroxine Sodium Injection and any potential adverse effects on the breastfed infant from Levothyroxine Sodium Injection or from the underlying maternal condition.

The safety and effectiveness of Levothyroxine Sodium Injection have not been established in pediatric patients.

See Section 2, Dosage and Administration, for full prescribing information in the geriatric patient population. Because of the increased prevalence of cardiovascular disease in the elderly, cautious use of Levothyroxine Sodium Injection in the elderly and in patients with known cardiac risk factors is advised. Atrial fibrillation is a common side effect associated with levothyroxine treatment in the elderly [see Dosage and Administration (2) and Warnings and Precautions (5)].

Serum creatinine and levothyroxine levels should be closely monitored in patients with severe renal impairment receiving intravenous levothyroxine with betadex sulfobutyl (SBECD) [See Clinical Pharmacology (12.3)].

In general, the signs and symptoms of overdosage with levothyroxine 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. Excessive doses of Levothyroxine Sodium Injection (greater than 500 mcg) are associated with cardiac complications in patients with underlying cardiac disease.

{ "type": "p", "children": [], "text": "In general, the signs and symptoms of overdosage with levothyroxine 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. Excessive doses of Levothyroxine Sodium Injection (greater than 500 mcg) are associated with cardiac complications in patients with underlying cardiac disease." }

Treatment of Overdosage

{ "type": "p", "children": [], "text": "\nTreatment of Overdosage\n" }

Levothyroxine Sodium Injection should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient.

{ "type": "p", "children": [], "text": "Levothyroxine Sodium Injection should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient." }

In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s medical status.

{ "type": "p", "children": [], "text": "In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s medical status." }

Levothyroxine sodium injection contains synthetic levothyroxine (L-thyroxine) sodium salt.  Levothyroxine sodium has an empirical formula of C15H10I4NNaO4, a molecular weight of 798.85 g/mol (anhydrous), and the following structural formula:

{ "type": "p", "children": [], "text": "Levothyroxine sodium injection contains synthetic levothyroxine (L-thyroxine) sodium salt.  Levothyroxine sodium has an empirical formula of C15H10I4NNaO4, a molecular weight of 798.85 g/mol (anhydrous), and the following structural formula:" }

Levothyroxine sodium injection is a sterile, preservative-free, clear, colorless to slightly yellow solution for intravenous administration available as 100 mcg/mL in a single-dose clear glass vial. Each mL of levothyroxine sodium injection also contains 0.05 mg arginine, USP; 80 mg betadex sulfobutyl ether sodium, USP; 0.05 mg edetate disodium, USP; and water for injection, USP. Sodium chloride, USP was added to adjust tonicity. Hydrochloric acid, NF and/or sodium hydroxide, NF may have been added for pH adjustment.

{ "type": "p", "children": [], "text": "Levothyroxine sodium injection is a sterile, preservative-free, clear, colorless to slightly yellow solution for intravenous administration available as 100 mcg/mL in a single-dose clear glass vial. Each mL of levothyroxine sodium injection also contains 0.05 mg arginine, USP; 80 mg betadex sulfobutyl ether sodium, USP; 0.05 mg edetate disodium, USP; and water for injection, USP. Sodium chloride, USP was added to adjust tonicity. Hydrochloric acid, NF and/or sodium hydroxide, NF may have been added for pH adjustment." }

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis.  Triiodothyronine (T3) and levothyroxine (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.

Thyroid hormone synthesis and secretion is regulated by the hypothalamic pituitary-thyroid axis.  Thyrotropin releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyrotropin stimulating hormone (TSH) from the anterior pituitary.  TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, T4 and T3, by the thyroid gland.  Circulating serum T3 and T4 levels exert a feedback effect on both TRH and TSH secretion.  When serum T3 and T4 levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increases.  TSH is used for the diagnosis of hypothyroidism and evaluation of levothyroxine therapy adequacy with other laboratory and clinical data [see Dosage (2.1)].   There are drugs known to affect thyroid hormones and TSH by various mechanisms and those examples are diazepam, ethioamide, lovastatin, metoclopramide, 6-mercaptopurine, nitroprusside, perphenazine, and thiazide diuretics.  Some drugs may cause a transient decrease in TSH secretion without hypothyroidism and those drugs (dose) are dopamine (greater than 1 mcg per kg per min), glucocorticoids (hydrocortisone greater than 100 mg per day or equivalent) and octreotide (greater than 100 mcg per day).

Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal maturation of the central nervous system and bone.  The metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids.  The protein anabolic effects of thyroid hormones are essential to normal growth and development.

Absorption – Levothyroxine Sodium Injection is administered via the intravenous route.  Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously. 

Distribution – Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone.  The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3.  Protein bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone.  Only unbound hormone is metabolically active.  Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [see Warnings and Precautions (5) and Drug Interactions (7)].   Thyroid hormones do not readily cross the placental barrier [see Warnings and Precautions (5) and Use in Specific Populations (8)]. Betadex sulfobutyl ether (SBECD) does not affect levothyroxine binding to plasma proteins.

Metabolism – T4 is slowly eliminated.  The major pathway of thyroid hormone metabolism is through sequential deiodination.  Approximately eighty percent of circulating T3 is derived from peripheral T4 by mono-deiodination.  The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues.  Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3).  T3 and rT3 are further deiodinated to diiodothyronine.  Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.

Elimination – Thyroid hormones are primarily eliminated by the kidneys.  A portion of the conjugated hormone reaches the colon unchanged, where it is hydrolyzed and eliminated in feces as the free hormones.  Urinary excretion of T4 decreases with age.

In patients with severe renal impairment or ESRD (eGFR of < 15 mL/min/1.73 m2), accumulation of SBECD occurs [see Renal Impairment 8.6].

Table 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients

<div class="scrollingtable"><table> <col width="13%"/> <col width="32%"/> <col width="16%"/> <col width="19%"/> <col width="20%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Hormone</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Ratio in Thyroglobulin</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Biologic Potency</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Half-Life (Days)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Protein Binding </span> <br/> <span class="Bold">(%)<span class="Sup">2</span></span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"> <p class="First">T<span class="Sub">4</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10 to 20</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6 to 8<span class="Sup">1</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">99.96</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">T<span class="Sub">3</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">≤ 2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">99.5</p> </td> </tr> </tbody> </table></div>

T4:  Levothyroxine

T3:  Liothyronine 13 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism. 2Includes TBG, TBPA, and TBA.

Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of Levothyroxine Sodium Injection.

No animal toxicology studies have been conducted with Levothyroxine Sodium Injection.

No clinical studies have been conducted with Levothyroxine Sodium Injection in patients with myxedema coma.  However, data from published literature support the intravenous use of levothyroxine sodium for the treatment of myxedema coma.

{ "type": "p", "children": [], "text": "No clinical studies have been conducted with Levothyroxine Sodium Injection in patients with myxedema coma.  However, data from published literature support the intravenous use of levothyroxine sodium for the treatment of myxedema coma." }

Levothyroxine Sodium Injection 100 mcg/mL is a clear, colorless to slightly yellow solution, supplied as1 mL per vial.

Package of 1 single-dose vial: NDC 24201-002-01

Protect from light and store product at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Drug product is preservative free.  Discard any unused portion.

Manufactured for:

Hikma Pharmaceuticals USA Inc.

Berkeley Heights, NJ 07922

www.hikma.com/us

Revised: 07/2024

462-046-00

NDC 24201-002-01     Levothyroxine Sodium Injection 100 mcg/mL

{ "type": "p", "children": [], "text": "\nNDC 24201-002-01    \nLevothyroxine \n\nSodium Injection\n\n100 mcg/mL\n" }

For Intravenous Use 1 mL Single-Dose Vial

{ "type": "p", "children": [], "text": "For Intravenous Use \n1 mL Single-Dose Vial" }

Discard any unused portion. Rx only

{ "type": "p", "children": [], "text": "Discard any unused portion. \nRx only" }

Hypothyroidism

TIROSINT is 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.

Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression

TIROSINT is indicated as an adjunct to surgery and radioiodine therapy in the management of adults and pediatric patients 6 years and older with thyrotropin-dependent well-differentiated thyroid cancer.

Limitations of Use:

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

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

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

Swallow TIROSINT capsules whole, do not cut, crush, or chew.

The dose of TIROSINT 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 TIROSINT may not be attained for 4 to 6 weeks.

Primary Hypothyroidism in Adults and in Adolescents in Whom Growth and Puberty are Complete

Start TIROSINT at the full replacement dose in otherwise healthy, non-elderly individuals who have been hypothyroid for only a short time (such as a few months).The average full replacement dose of TIROSINT is approximately 1.6 mcg per kg per day (for example: 100-125 mcg per day for a 70 kg adult).

Adjust the dose by 12.5 to 25 mcg increments every 4 to 6 weeks until the patient is clinically euthyroid and the serum TSH returns to normal. Doses greater than 200 mcg per day are seldom required. An inadequate response to daily doses greater than 300 mcg per day is rare and may indicate poor compliance, malabsorption, drug interactions, or a combination of these factors.

For elderly patients or patients with underlying cardiovascular disease, start with a dose of 12.5 to 25 mcg per day. Increase the dose every 6 to 8 weeks, as needed, until the patient is clinically euthyroid and the serum TSH returns to normal. The full replacement dose of TIROSINT may be less than 1 mcg per kg per day in elderly patients.

In patients with severe longstanding hypothyroidism, start with a dose of 12.5 to 25 mcg per day. Adjust the dose in 12.5 to 25 mcg increments every 2 to 4 weeks until the patient is clinically euthyroid and the serum TSH level is normalized.

Secondary or Tertiary Hypothyroidism

Start TIROSINT at the full replacement dose in otherwise healthy, non-elderly individuals. Start with a lower dose in elderly patients with underlying cardiovascular disease or patients with severe longstanding hypothyroidism as described above. Serum TSH is not a reliable measure of TIROSINT dose adequacy in patients with secondary or tertiary hypothyroidism, and should not be used to monitor therapy. Use the serum free-T4 level to monitor adequacy of therapy in this patient population. Titrate TIROSINT dosing per above instructions until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range.

Pediatric Dosage - Congenital or Acquired Hypothyroidism

Only administer TIROSINT to pediatric patients 6 years and older who are able to swallow an intact capsule .

The recommended daily dose of TIROSINT in pediatric patients with hypothyroidism is based on body weight and changes with age as described in Table 1. Start TIROSINT at the full daily dose in most pediatric patients. Start at a lower dose in children at risk for hyperactivity (see below). Monitor for clinical and laboratory response [see Dosage and Administration (2.4)] .

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1: TIROSINT Dosing Guidelines for Pediatric Hypothyroidism</span> </caption> <col align="left" valign="top" width="60%"/> <col align="center" valign="top" width="40%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Age</th><th align="center" class="Rrule">Daily Dose Per Kg Body Weight <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>The dose should be adjusted based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4)] . </dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">6-12 years</td><td align="center" class="Rrule">4-5 mcg/kg/day</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Greater than 12 years but growth and puberty incomplete</td><td align="center" class="Rrule">2-3 mcg/kg/day</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Growth and puberty complete</td><td align="center" class="Rrule">1.6 mcg/kg/day</td> </tr> </tbody> </table></div>

Children at risk for hyperactivity: To minimize the risk of hyperactivity in children, start at one-fourth the recommended full replacement dose, and increase on a weekly basis by one-fourth the full-recommended replacement dose until the full recommended replacement dose is reached.

Pregnancy

Preexisting Hypothyroidism: TIROSINT dose requirements may increase during pregnancy . Measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at a minimum, during each trimester of pregnancy. In patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range. For patients with serum TSH above the normal trimester specific range, increase the dose of TIROSINT by 12.5 to 25 mcg per day and measure TSH every four weeks until a stable TIROSINT dose is reached and serum TSH is within the normal trimester specific range. Reduce TIROSINT dosage to pre-pregnancy levels immediately after delivery and measure serum TSH levels 4 to 8 weeks postpartum to ensure the TIROSINT dose is appropriate.

New Onset Hypothyroidism: Normalize thyroid function as rapidly as possible. In patients with moderate to severe signs and symptoms of hypothyroidism, start TIROSINT at the full replacement dose (1.6 mcg per kg body weight per day). In patients with mild hypothyroidism (TSH < 10 mIU per Liter), start TIROSINT at 1.0 mcg per kg body weight per day. Evaluate serum TSH every 4 weeks and adjust TIROSINT dosage until serum TSH is within the normal trimester specific range [see Use in Specific Populations (8.1)].

TSH Suppression in Well-Differentiated Thyroid Cancer

Generally, TSH is suppressed to below 0.1 mIU per Liter, and this usually requires a TIROSINT dose of greater than 2 mcg per kg per day. However, in patients with high-risk tumors, the target level for TSH suppression may be lower.

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

Adults

In adult patients with primary hypothyroidism, monitor serum TSH levels after an interval of 6 to 8 weeks after any change in dose. In patients on a stable and appropriate replacement dose, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient's clinical status.

Pediatrics

In patients with congenital hypothyroidism, assess the adequacy of replacement therapy by measuring both serum TSH and total or free-T4. Monitor TSH and total or free-T4 in children is as follows: at 2 and 4 weeks after the initiation of treatment 2 weeks after any change in dosage, and then every 3 to 12 months thereafter following dose stabilization until growth is completed. Poor compliance or abnormal values may necessitate more frequent monitoring. Perform routine clinical examination, including assessment of mental and physical growth and development, and bone maturation at regular intervals.

While the general aim of therapy is to normalize the serum TSH level, TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of the pituitary-thyroid feedback. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of TIROSINT therapy and/or of the serum TSH to decrease below 20 mIU per Liter within 4 weeks may indicate the child is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of TIROSINT [see Warnings and Precautions (5.4) and Use in Specific Populations (8.4)] .

Secondary (Pituitary) and Tertiary (Hypothalamic) Hypothyroidism

Monitor serum free-T4 levels maintain in the upper half of the normal range in these patients.

TIROSINT 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:

{ "type": "p", "children": [], "text": "TIROSINT 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:" }

<div class="scrollingtable"><table border="1" width="60%"> <colgroup> <col align="center" valign="top" width="55%"/> <col align="center" valign="top" width="45%"/> </colgroup> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Strength (mcg)</th><th align="center" class="Rrule">Imprint Code</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">13</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">A</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">25</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">E</span></span></td> </tr> <tr> <td align="center" class="Lrule Rrule">37.5</td><td align="center" class="Rrule"><span class="Bold"><span class="Underline">O</span></span></td> </tr> <tr> <td align="center" class="Lrule Rrule">44</td><td align="center" class="Rrule"><span class="Bold"><span class="Underline">R</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">50</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">G</span></span></td> </tr> <tr> <td align="center" class="Lrule Rrule">62.5</td><td align="center" class="Rrule"><span class="Bold"><span class="Underline">L</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">75</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">H</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">88</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">J</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">100</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">K</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">112</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">M</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">125</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">N</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">137</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">P</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">150</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">S</span></span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">175</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">U</span></span></td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">200</td><td align="center" class="Rrule"><span class="Underline"><span class="Bold">Y</span></span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" width=\"60%\">\n<colgroup>\n<col align=\"center\" valign=\"top\" width=\"55%\"/>\n<col align=\"center\" valign=\"top\" width=\"45%\"/>\n</colgroup>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\">Strength (mcg)</th><th align=\"center\" class=\"Rrule\">Imprint Code</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\">13</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">A</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">25</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">E</span></span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\">37.5</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\"><span class=\"Underline\">O</span></span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\">44</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\"><span class=\"Underline\">R</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">50</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">G</span></span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\">62.5</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\"><span class=\"Underline\">L</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">75</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">H</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">88</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">J</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">100</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">K</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">112</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">M</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">125</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">N</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">137</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">P</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">150</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">S</span></span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">175</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">U</span></span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Lrule Rrule\">200</td><td align=\"center\" class=\"Rrule\"><span class=\"Underline\"><span class=\"Bold\">Y</span></span></td>\n</tr>\n</tbody>\n</table></div>" }

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

{ "type": "p", "children": [], "text": "TIROSINT is contraindicated in patients with uncorrected adrenal insufficiency \n \n \n [see \n \n \n Warnings and Precautions (5.3)].\n \n \n \n" }

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

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.

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 TIROSINT [see Contraindications (4)].

TIROSINT has a narrow therapeutic index. Over- or under-treatment with TIROSINT 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 TIROSINT 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 TIROSINT and adjust the dose as necessary [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

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)] .

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

Adverse Reactions in Children

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in children with resultant compromised adult height.

Hypersensitivity Reactions

Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

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 TIROSINT (see Tables 2 to 5 below).

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 2: Drugs That May Decrease T4 Absorption (Hypothyroidism)</span> </caption> <col align="left" valign="top" width="45%"/> <col align="left" valign="top" width="55%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" colspan="2">Potential impact: Concurrent use may reduce the efficacy of TIROSINT by binding and delaying or preventing absorption, potentially resulting in hypothyroidism</th> </tr> <tr class="Last"> <th align="center" class="Lrule Rrule">Drug or Drug Class</th><th align="center" class="Rrule">Effect</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Calcium Carbonate <br/>Ferrous Sulfate </td><td align="left" class="Rrule">Calcium carbonate may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex. Administer TIROSINT at least 4 hours apart from these agents.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Orlistat</td><td align="left" class="Rrule">Monitor patients treated concomitantly with orlistat and TIROSINT for changes in thyroid function.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Bile Acid Sequestrants <br/>-Colesevelam <br/>-Cholestyramine <br/>-Colestipol <br/>Ion Exchange Resins <br/>-Kayexalate <br/>-Sevelamer </td><td align="left" class="Rrule">Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer TIROSINT at least 4 hours prior to these drugs or monitor thyrotropin (TSH) levels.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Other drugs: <br/>Proton Pump Inhibitors <br/>Sucralfate <br/>Antacids <br/>- Aluminum &amp; Magnesium Hydroxides <br/>- Simethicone </td><td align="left" class="Rrule">Gastric acidity is an essential requirement for adequate absorption of levothyroxine. Sucralfate, antacids and proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce levothyroxine absorption. Monitor patients appropriately</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 3: Drugs That May Alter T4 and Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism)</span> </caption> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Drug or Drug Class</th><th align="center" class="Rrule">Effect</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Clofibrate <br/>Estrogen-containing oral contraceptives <br/>Estrogens (oral) <br/>Heroin / Methadone <br/>5-Fluorouracil <br/>Mitotane <br/>Tamoxifen </td><td align="left" class="Rrule">These drugs may increase serum thyroxine-binding globulin (TBG) concentration.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Androgens / Anabolic Steroids <br/>Asparaginase <br/>Glucocorticoids <br/>Slow-Release Nicotinic Acid </td><td align="left" class="Rrule">These drugs may decrease serum TBG concentration.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2">Potential impact (below) <span class="Bold">:</span> Administration of these agents with TIROSINT results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Salicylates (&gt; 2 g/day)</td><td align="left" class="Rrule">Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4 is followed by return of FT4 to normal levels with sustained therapeutic serum salicylate concentrations, although total T4 levels may decrease by as much as 30%.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Other drugs: <br/>Carbamazepine <br/>Furosemide (&gt; 80 mg IV) <br/>Heparin <br/>Hydantoins <br/>Non-Steroidal Anti-inflammatory Drugs <br/>- Fenamates </td><td align="left" class="Rrule">These drugs may cause protein-binding site displacement <span class="Bold">.</span> Furosemide has been shown to inhibit the protein binding of T4 to TBG and albumin, causing an increased free-T4 fraction in serum. Furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower the total T4 level. Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Closely monitor thyroid hormone parameters. </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 4: Drugs That May Alter Hepatic Metabolism of T4 (Hypothyroidism)</span> </caption> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" colspan="2">Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased TIROSINT requirements.</th> </tr> <tr class="Last"> <th align="center" class="Lrule Rrule">Drug or Drug Class</th><th align="center" class="Rrule">Effect</th> </tr> </thead> <tbody> <tr class="First Last"> <td align="left" class="Lrule Rrule">Phenobarbital <br/>Rifampin </td><td align="left" class="Rrule">Phenobarbital has been shown to reduce the response to thyroxine. Phenobarbital increases L-thyroxine metabolism by inducing uridine 5'-diphospho-glucuronosyltransferase (UGT) and leads to a lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Rifampin has been shown to accelerate the metabolism of levothyroxine.</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 5: Drugs That May Decrease Conversion of T4 to T3</span> </caption> <col align="left" valign="top" width="55%"/> <col align="left" valign="top" width="45%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" colspan="2">Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T4 to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased.</th> </tr> <tr class="Last"> <th align="center" class="Lrule Rrule">Drug or Drug Class</th><th align="center" class="Rrule">Effect</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Beta-adrenergic antagonists <br/>(e.g., Propranolol &gt; 160 mg/day) </td><td align="left" class="Rrule">In patients treated with large doses of propranolol (&gt; 160 mg/day), T3 and T4 levels change, TSH levels remain normal, and patients are clinically euthyroid. Actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Glucocorticoids <br/>(e.g., Dexamethasone ≥ 4 mg/day) </td><td align="left" class="Rrule">Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels. However, long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (see <span class="Bold"><a href="#t3">Table 3</a></span> above). </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Other: <br/>Amiodarone </td><td align="left" class="Rrule">Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, and decrease or normal free-T3) in clinically euthyroid patients.</td> </tr> </tbody> </table></div>

Addition of TIROSINT 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)] .

TIROSINT 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 TIROSINT dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

TIROSINT 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.

Concurrent use of tricyclic (e.g., Amitriptyline) or tetracyclic (e.g., Maprotiline) antidepressants and TIROSINT 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. TIROSINT may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on TIROSINT may result in increased TIROSINT requirements.

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

Concurrent use of sympathomimetics and TIROSINT 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.

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

Consumption of certain foods may affect TIROSINT 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 TIROSINT from the GI tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability.

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.

Risk Summary

Experience with levothyroxine use in pregnant women, including data from post-marketing studies, have not reported increased rates of major birth defects or miscarriages [see Data]. There are risks to the mother and fetus associated with untreated hypothyroidism in pregnancy. Since thyroid-stimulating hormone (TSH) levels may increase during pregnancy, TSH should be monitored and TIROSINT dosage adjusted during pregnancy [see Clinical Considerations] . There are no animal studies conducted with levothyroxine during pregnancy. TIROSINT should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Maternal hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, and premature delivery. Untreated maternal hypothyroidism may have an adverse effect on fetal neurocognitive development.

Dose Adjustments During Pregnancy and the Postpartum Period

Pregnancy may increase TIROSINT requirements. Serum TSH level should be monitored and the TIROSINT dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the TIROSINT dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3)].

Data

Human Data

Levothyroxine is approved for use as a replacement therapy for hypothyroidism. There is a long experience of levothyroxine use in pregnant women, including data from post-marketing studies that have not reported increased rates of fetal malformations, miscarriages or other adverse maternal or fetal outcomes associated with levothyroxine use in pregnant women.

Risk Summary

Limited published studies report that levothyroxine is present in human milk. However, there is insufficient information to determine the effects of levothyroxine on the breastfed infant and no available information on the effects of levothyroxine on milk production. Adequate levothyroxine treatment during lactation may normalize milk production in hypothyroid lactating mothers. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TIROSINT and any potential adverse effects on the breastfed infant from TIROSINT or from the underlying maternal condition.

TIROSINT is indicated for use in pediatric patients 6 years and older. The initial dose of TIROSINT 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 TIROSINT 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.

Congenital Hypothyroidism [see Dosage and Administration (2.3, 2.4)]

Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism on intellectual development as well as on overall physical growth and maturation. Therefore, initiate levothyroxine therapy immediately upon diagnosis. Levothyroxine is generally continued for life in these patients.

Closely monitor children during the first two weeks of TIROSINT therapy for cardiac overload and arrhythmias.

Closely monitor patients to avoid undertreatment and overtreatment. Undertreatment may have deleterious effects on intellectual development and linear growth. Overtreatment may adversely affect the tempo of brain maturation and accelerate the bone age with resultant premature closure of the epiphyses and compromised adult stature.

Acquired Hypothyroidism in Pediatric Patients

Closely monitor patients to avoid undertreatment and overtreatment. Undertreatment may result in poor school performance due to impaired concentration and slowed mentation and in reduced adult height. Overtreatment may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature.

Treated children may manifest a period of catch-up growth, which may be adequate in some cases to normalize adult height. In children with severe or prolonged hypothyroidism, catch-up growth may not be adequate to normalize adult height.

Because of the increased prevalence of cardiovascular disease among the elderly, initiate TIROSINT 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 .

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.

{ "type": "p", "children": [], "text": "The signs and symptoms of overdosage are those of hyperthyroidism \n \n \n [see \n \n \n Warnings and Precautions (5) and \n \n \n Adverse Reactions (6)].\n \n \n 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.\n \n\n " }

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

{ "type": "p", "children": [], "text": "Reduce the TIROSINT 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.

{ "type": "p", "children": [], "text": "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." }

TIROSINT (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:

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

TIROSINT (levothyroxine sodium) capsules are amber-colored, round/biconvex capsules containing a viscous amber-colored liquid.

{ "type": "p", "children": [], "text": "TIROSINT (levothyroxine sodium) capsules are amber-colored, round/biconvex capsules containing a viscous amber-colored liquid. " }

The inactive ingredients in TIROSINT are gelatin, glycerin and water.

{ "type": "p", "children": [], "text": "The inactive ingredients in TIROSINT are gelatin, glycerin and water." }

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.

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.

Absorption

Absorption of orally administered T 4 from the gastrointestinal (GI) tract ranges from 40% to 80%. The majority of the levothyroxine dose is absorbed from the jejunum and upper ileum. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans. Dietary fiber decreases the bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption. [see Drug Interactions (7)]

Distribution

Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and thyroxine-binding albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [see Drug Interactions (7)]. Thyroid hormones do not readily cross the placental barrier [see Use in Specific Populations (8.1)].

Elimination

Metabolism

T4 is slowly eliminated (see Table 6) . The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and rT3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.

Excretion

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 6: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients</span> </caption> <col align="center" valign="middle" width="23%"/> <col align="center" valign="middle" width="24%"/> <col align="center" valign="middle" width="17%"/> <col align="center" valign="middle" width="17%"/> <col align="center" valign="middle" width="19%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Hormone</th><th align="center" class="Rrule">Ratio in Thyroglobulin</th><th align="center" class="Rrule">Biologic Potency</th><th align="center" class="Rrule">Half-Life <br/>(Days) </th><th align="center" class="Rrule">Protein Binding <br/>(%) <a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Includes TBG, TBPA and TBA.</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">†</a> </dt> <dd>3 – 4 days in hyperthyroidism, 9 – 10 days in hypothyroidism.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">Levothyroxine (T4)</td><td align="center" class="Rrule">10 – 20</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">6 – 7 <a class="Sup" href="#footnote-3" name="footnote-reference-3">†</a></td><td align="center" class="Rrule">99.96</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Liothyronine (T3)</td><td align="center" class="Rrule">1</td><td align="center" class="Rrule">4</td><td align="center" class="Rrule">≤ 2</td><td align="center" class="Rrule">99.5</td> </tr> </tbody> </table></div>

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

TIROSINT (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:

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 7: TIROSINT Packaging Description - Boxes of 30 capsules, consisting of 3 blisters with 10 capsules each</span> </caption> <colgroup> <col align="center" valign="bottom" width="24%"/> <col align="center" valign="bottom" width="24%"/> <col align="center" valign="bottom" width="18%"/> <col align="center" valign="bottom" width="34%"/> </colgroup> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" valign="top">Strength (mcg)</th><th align="center" class="Rrule" valign="top">Color <a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a></th><th align="center" class="Rrule" valign="top">Imprint Code</th><th align="center" class="Rrule" valign="top">NDC</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>Shown on box and blister packing, not on individual capsules.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">13</td><td align="center" class="Rrule">Green</td><td align="center" class="Rrule"><span class="Bold">A</span></td><td align="center" class="Rrule">71858-0005-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">25</td><td align="center" class="Rrule">Orange</td><td align="center" class="Rrule"><span class="Bold">E</span></td><td align="center" class="Rrule">71858-0010-4</td> </tr> <tr> <td align="center" class="Lrule Rrule">37.5</td><td align="center" class="Rrule">Dark Blue</td><td align="center" class="Rrule"><span class="Bold">O</span></td><td align="center" class="Rrule">71858-0012-4</td> </tr> <tr> <td align="center" class="Lrule Rrule">44</td><td align="center" class="Rrule">Red</td><td align="center" class="Rrule"><span class="Bold">R</span></td><td align="center" class="Rrule">71858-0013-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">50</td><td align="center" class="Rrule">White</td><td align="center" class="Rrule"><span class="Bold">G</span></td><td align="center" class="Rrule">71858-0015-4</td> </tr> <tr> <td align="center" class="Lrule Rrule">62.5</td><td align="center" class="Rrule">Grey</td><td align="center" class="Rrule">L</td><td align="center" class="Rrule">71858-0017-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">75</td><td align="center" class="Rrule">Purple</td><td align="center" class="Rrule"><span class="Bold">H</span></td><td align="center" class="Rrule">71858-0020-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">88</td><td align="center" class="Rrule">Olive</td><td align="center" class="Rrule"><span class="Bold">J</span></td><td align="center" class="Rrule">71858-0025-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">100</td><td align="center" class="Rrule">Yellow</td><td align="center" class="Rrule"><span class="Bold">K</span></td><td align="center" class="Rrule">71858-0030-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">112</td><td align="center" class="Rrule">Rose</td><td align="center" class="Rrule"><span class="Bold">M</span></td><td align="center" class="Rrule">71858-0035-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">125</td><td align="center" class="Rrule">Brown</td><td align="center" class="Rrule"><span class="Bold">N</span></td><td align="center" class="Rrule">71858-0040-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">137</td><td align="center" class="Rrule">Turquoise</td><td align="center" class="Rrule"><span class="Bold">P</span></td><td align="center" class="Rrule">71858-0045-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">150</td><td align="center" class="Rrule">Blue</td><td align="center" class="Rrule"><span class="Bold">S</span></td><td align="center" class="Rrule">71858-0050-4</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">175</td><td align="center" class="Rrule">Lilac</td><td align="center" class="Rrule"><span class="Bold">U</span></td><td align="center" class="Rrule">71858-0055-4</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">200</td><td align="center" class="Rrule">Pink</td><td align="center" class="Rrule"><span class="Bold">Y</span></td><td align="center" class="Rrule">71858-0060-4</td> </tr> </tbody> </table></div>

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 (TIROSINT).

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°-30°C (59-86°F) [see USP Controlled Room Temperature]. TIROSINT 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.

Dosing and Administration

Important Information

Adverse Reactions

Manufactured for IBSA Pharma Inc. by:

{ "type": "p", "children": [], "text": "Manufactured for IBSA Pharma Inc. by:" }

IBSA Institut Biochimique SA 6912 Pazzallo Switzerland

{ "type": "p", "children": [], "text": "IBSA Institut Biochimique SA\n \n\n6912 Pazzallo\n \n\nSwitzerland\n " }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

IBSA Pharma Inc., Parsippany, NJ 07054 USA

{ "type": "p", "children": [], "text": "IBSA Pharma Inc.,\n \n\nParsippany, NJ 07054\n \n\nUSA\n " }

<div class="scrollingtable"><table width="100%"> <colgroup> <col align="left" valign="top" width="34%"/> <col align="left" valign="top" width="33%"/> <col align="left" valign="top" width="33%"/> </colgroup> <tfoot> <tr class="First Last"> <td align="left" colspan="2">This Patient Information has been approved by the U.S. Food and Drug Administration</td><td align="right">Issued: October 2022</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="3"><span class="Bold">PATIENT INFORMATION <br/> <br/> TIROSINT® </span> [tee-row-sent] <br/> <br/> (levothyroxine sodium) <br/> <br/> capsules, for oral use </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What is the most important information I should know about TIROSINT?</span> <ul class="Disc"> <li> <span class="Bold">Do not use TIROSINT to treat weight problems or weight loss</span>. </li> <li> <span class="Bold">Do not take more TIROSINT than your doctor prescribes for you to take. Over dosage or taking too much TIROSINT may cause life-threatening side effects or death. </span> </li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What is TIROSINT?</span> <br/> <br/> TIROSINT is a prescription medicine that contains a hormone called levothyroxine which is normally produced by the thyroid gland. TIROSINT is used to treat adults and children 6 years of age or older: <ul class="Disc"> <li>to replace or give extra levothyroxine in people whose thyroid does not produce enough of this hormone.</li> <li>who need surgery and radioiodine therapy to manage a type of thyroid cancer called thyroid-dependent well-differentiated thyroid cancer.</li> </ul> TIROSINT should not be used to treat people who are recovering from swelling of the thyroid gland (thyroiditis) and whose bodies do not produce enough levothyroxine for a short time. <br/> <br/> TIROSINT is unsuitable for children less than 6 years of age or who may be unable to swallow an intact capsule. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Do not take TIROSINT:</span> <ul class="Disc"> <li>if your adrenal glands are not working well and you have not been treated for this problem.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Before you take TIROSINT, tell your doctor about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have or had heart problems.</li> <li>have or had thyroid nodules.</li> <li>have kidney or pituitary gland problems.</li> <li>have any food or drug allergies.</li> <li>have a low red blood cell count (anemia).</li> <li>have diabetes.</li> <li>have weak bones (osteoporosis).</li> <li>have or had a history of blood clotting problems.</li> <li>have recently received radiation therapy with iodine (such as I-131).</li> <li>are pregnant or plan to become pregnant. TIROSINT may harm your unborn baby. Your doctor may need to change your TIROSINT dose while you are pregnant.</li> <li>are breastfeeding. TIROSINT can pass into your milk. Talk to your doctor about the best way to feed your baby if you take TIROSINT.</li> </ul> Tell your doctor about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. TIROSINT may affect the way other medicines work, and other medicines may affect how TIROSINT works. You can ask your doctor or pharmacist for a list of medicines that interact with TIROSINT. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">How should I take TIROSINT?</span> <ul class="Disc"> <li>Take TIROSINT exactly as your doctor tells you to take it.</li> <li>Your doctor will tell you how much TIROSINT to take each day.</li> <li> <span class="Bold">Swallow TIROSINT capsules whole</span>. Do not cut, crush, or chew TIROSINT capsules before swallowing. If you or your child cannot swallow TIROSINT capsules whole, tell your doctor. You may need a different medicine. </li> <li>Your doctor may change your dose, if needed.</li> <li>Take your dose of TIROSINT 1 time each day, 30 minutes to 1 hour before breakfast, on an empty stomach.</li> <li>Certain medicines can interfere with how TIROSINT is absorbed by your body. Take TIROSINT: <ul class="Circle"> <li> <span class="Bold">at least 4 hours before or after</span> you take medicines that contain calcium carbonate or iron (ferrous sulfate). </li> <li> <span class="Bold">at least 4 hours before</span> you take medicines that contain bile acid sequestrants or ion exchange resins. </li> </ul> </li> <li> <span class="Bold">Know the medicines that you take. Ask your doctor or pharmacist for a list of these medicines, if you are not sure.</span> </li> <li>Certain foods including soybean flour, cotton seed meal, walnuts, and dietary fiber can affect your treatment and dose of TIROSINT. Talk to your doctor if you eat or drink these foods.</li> <li> <span class="Bold">Do not</span> remove TIROSINT capsules from the original blister package until you are ready to take them. </li> <li>Your doctor should do certain blood tests while you are taking TIROSINT and may change your daily dose of TIROSINT as needed. You should not stop taking TIROSINT or change your dose unless your doctor tells you to.</li> <li>It may take weeks before you notice your symptoms getting better. Keep using this medicine even if you feel well.</li> <li>If you take too much TIROSINT or overdose, call your doctor or poison control center at 1-800-222-1222, or go to the nearest hospital emergency room right away.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the possible side effects of TIROSINT? <br/> <br/> TIROSINT may cause serious side effects, including: </span> <ul class="Disc"> <li> <span class="Bold">heart problems. You may experience an increased heart rate, chest pain and irregular heartbeat.</span> Your risk of developing heart problems may be greater if you are elderly, have heart problems, or if you take too much TIROSINT. Your doctor may reduce your dose or stop treatment with TIROSINT for a while if you develop heart problems. </li> <li>worsening diabetic control. If you are diabetic, it may be harder to control your blood sugar levels causing hyperglycemia while taking TIROSINT. Check your blood sugar levels closely after starting, changing, or stopping treatment with TIROSINT. Your doctor may have to change your diabetes treatment plan.</li> <li> <span class="Bold">weak or brittle bones.</span> Your risk of developing weak or brittle bones may be greater if you are post-menopausal or you take too much TIROSINT. </li> </ul> The most common side effects of TIROSINT include: </td> </tr> <tr> <td align="left" class="Lrule"> <ul class="Disc"> <li>irregular heartbeat</li> <li>chest pain</li> <li>shortness of breath</li> <li>leg cramps</li> <li>headache</li> <li>nervousness</li> <li>hives or skin rash</li> </ul> </td><td align="left"> <ul class="Disc"> <li>irritability</li> <li>sleep problems (insomnia)</li> <li>tremors</li> <li>muscle weakness</li> <li>change in appetite</li> <li>weight loss</li> </ul> </td><td align="left" class="Rrule"> <ul class="Disc"> <li>vomiting</li> <li>diarrhea</li> <li>sweating a lot</li> <li>heat intolerance</li> <li>fever</li> <li>changes in menstrual period</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3">Other side effects may include: <ul class="Disc"> <li>partial hair loss during the first months of treatment with TIROSINT. This usually lasts a short period of time (temporary).</li> </ul> These are not all the possible side effects of TIROSINT. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. <br/> <br/> You may also report side effects to IBSA Pharma Inc. at 1-800-587-3513 or www.fda.gov/medwatch. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">How should I store TIROSINT?</span> <ul class="Disc"> <li>Store TIROSINT at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Store TIROSINT away from heat, light, and moisture.</li> <li>Keep TIROSINT in the original blister pack until you are ready to use it.</li> </ul> <span class="Bold">Keep TIROSINT and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">General information about the safe and effective use of TIROSINT</span> <br/> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TIROSINT for a condition for which it was not prescribed. Do not give TIROSINT to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about TIROSINT that is written for health professionals. </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the ingredients in TIROSINT? <br/> <br/> Active ingredient </span>: levothyroxine sodium <br/> <br/> <span class="Bold">Inactive ingredients</span>: gelatin, glycerin, and water <br/> <br/> Manufactured by: IBSA Institut Biochimique SA, 6912 Pazzallo, Switzerland; <br/> <br/> Marketed and distributed by: IBSA Pharma Inc., Parsippany, NJ 07054 USA <br/> <br/> For more information, go to www.tirosint.com or call 1-800-587-3513. </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<colgroup>\n<col align=\"left\" valign=\"top\" width=\"34%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n</colgroup>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"2\">This Patient Information has been approved by the U.S. Food and Drug Administration</td><td align=\"right\">Issued: October 2022</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">PATIENT INFORMATION\n <br/>\n<br/>\n\t\t\tTIROSINT® \n </span> [tee-row-sent]\n <br/>\n<br/>\n\t\t\t(levothyroxine sodium)\n <br/>\n<br/>\n\t\t\tcapsules, for oral use\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What is the most important information I should know about TIROSINT?</span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Do not use TIROSINT to treat weight problems or weight loss</span>.\n </li>\n<li>\n<span class=\"Bold\">Do not take more TIROSINT than your doctor prescribes for you to take. Over dosage or taking too much TIROSINT may cause life-threatening side effects or death. </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What is TIROSINT?</span>\n<br/>\n<br/>\n\t\t\tTIROSINT is a prescription medicine that contains a hormone called levothyroxine which is normally produced by the thyroid gland. TIROSINT is used to treat adults and children 6 years of age or older:\n\t\t\t\n <ul class=\"Disc\">\n<li>to replace or give extra levothyroxine in people whose thyroid does not produce enough of this hormone.</li>\n<li>who need surgery and radioiodine therapy to manage a type of thyroid cancer called thyroid-dependent well-differentiated thyroid cancer.</li>\n</ul>\n\t\t\tTIROSINT should not be used to treat people who are recovering from swelling of the thyroid gland (thyroiditis) and whose bodies do not produce enough levothyroxine for a short time.\n <br/>\n<br/>\n\t\t\tTIROSINT is unsuitable for children less than 6 years of age or who may be unable to swallow an intact capsule.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Do not take TIROSINT:</span>\n<ul class=\"Disc\">\n<li>if your adrenal glands are not working well and you have not been treated for this problem.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Before you take TIROSINT, tell your doctor about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have or had heart problems.</li>\n<li>have or had thyroid nodules.</li>\n<li>have kidney or pituitary gland problems.</li>\n<li>have any food or drug allergies.</li>\n<li>have a low red blood cell count (anemia).</li>\n<li>have diabetes.</li>\n<li>have weak bones (osteoporosis).</li>\n<li>have or had a history of blood clotting problems.</li>\n<li>have recently received radiation therapy with iodine (such as I-131).</li>\n<li>are pregnant or plan to become pregnant. TIROSINT may harm your unborn baby. Your doctor may need to change your TIROSINT dose while you are pregnant.</li>\n<li>are breastfeeding. TIROSINT can pass into your milk. Talk to your doctor about the best way to feed your baby if you take TIROSINT.</li>\n</ul>\n\t\t\tTell your doctor about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements. TIROSINT may affect the way other medicines work, and other medicines may affect how TIROSINT works. You can ask your doctor or pharmacist for a list of medicines that interact with TIROSINT.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">How should I take TIROSINT?</span>\n<ul class=\"Disc\">\n<li>Take TIROSINT exactly as your doctor tells you to take it.</li>\n<li>Your doctor will tell you how much TIROSINT to take each day.</li>\n<li>\n<span class=\"Bold\">Swallow TIROSINT capsules whole</span>. Do not cut, crush, or chew TIROSINT capsules before swallowing. If you or your child cannot swallow TIROSINT capsules whole, tell your doctor. You may need a different medicine.\n </li>\n<li>Your doctor may change your dose, if needed.</li>\n<li>Take your dose of TIROSINT 1 time each day, 30 minutes to 1 hour before breakfast, on an empty stomach.</li>\n<li>Certain medicines can interfere with how TIROSINT is absorbed by your body. Take TIROSINT:\n\t\t\t\t\n <ul class=\"Circle\">\n<li>\n<span class=\"Bold\">at least 4 hours before or after</span> you take medicines that contain calcium carbonate or iron (ferrous sulfate).\n </li>\n<li>\n<span class=\"Bold\">at least 4 hours before</span> you take medicines that contain bile acid sequestrants or ion exchange resins.\n </li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Know the medicines that you take. Ask your doctor or pharmacist for a list of these medicines, if you are not sure.</span>\n</li>\n<li>Certain foods including soybean flour, cotton seed meal, walnuts, and dietary fiber can affect your treatment and dose of TIROSINT. Talk to your doctor if you eat or drink these foods.</li>\n<li>\n<span class=\"Bold\">Do not</span> remove TIROSINT capsules from the original blister package until you are ready to take them.\n </li>\n<li>Your doctor should do certain blood tests while you are taking TIROSINT and may change your daily dose of TIROSINT as needed. You should not stop taking TIROSINT or change your dose unless your doctor tells you to.</li>\n<li>It may take weeks before you notice your symptoms getting better. Keep using this medicine even if you feel well.</li>\n<li>If you take too much TIROSINT or overdose, call your doctor or poison control center at 1-800-222-1222, or go to the nearest hospital emergency room right away.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the possible side effects of TIROSINT?\n <br/>\n<br/>\n\t\t\tTIROSINT may cause serious side effects, including: \n </span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">heart problems. You may experience an increased heart rate, chest pain and irregular heartbeat.</span> Your risk of developing heart problems may be greater if you are elderly, have heart problems, or if you take too much TIROSINT. Your doctor may reduce your dose or stop treatment with TIROSINT for a while if you develop heart problems.\n </li>\n<li>worsening diabetic control. If you are diabetic, it may be harder to control your blood sugar levels causing hyperglycemia while taking TIROSINT. Check your blood sugar levels closely after starting, changing, or stopping treatment with TIROSINT. Your doctor may have to change your diabetes treatment plan.</li>\n<li>\n<span class=\"Bold\">weak or brittle bones.</span> Your risk of developing weak or brittle bones may be greater if you are post-menopausal or you take too much TIROSINT.\n </li>\n</ul>\n\t\t\tThe most common side effects of TIROSINT include:\n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\">\n<ul class=\"Disc\">\n<li>irregular heartbeat</li>\n<li>chest pain</li>\n<li>shortness of breath</li>\n<li>leg cramps</li>\n<li>headache</li>\n<li>nervousness</li>\n<li>hives or skin rash</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>irritability</li>\n<li>sleep problems (insomnia)</li>\n<li>tremors</li>\n<li>muscle weakness</li>\n<li>change in appetite</li>\n<li>weight loss</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Disc\">\n<li>vomiting</li>\n<li>diarrhea</li>\n<li>sweating a lot</li>\n<li>heat intolerance</li>\n<li>fever</li>\n<li>changes in menstrual period</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">Other side effects may include:\n\t\t\t\n <ul class=\"Disc\">\n<li>partial hair loss during the first months of treatment with TIROSINT. This usually lasts a short period of time (temporary).</li>\n</ul>\n\t\t\tThese are not all the possible side effects of TIROSINT. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.\n <br/>\n<br/>\n\t\t\tYou may also report side effects to IBSA Pharma Inc. at 1-800-587-3513 or www.fda.gov/medwatch.\n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">How should I store TIROSINT?</span>\n<ul class=\"Disc\">\n<li>Store TIROSINT at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Store TIROSINT away from heat, light, and moisture.</li>\n<li>Keep TIROSINT in the original blister pack until you are ready to use it.</li>\n</ul>\n<span class=\"Bold\">Keep TIROSINT and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">General information about the safe and effective use of TIROSINT</span>\n<br/>\n<br/>\n\t\t\tMedicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TIROSINT for a condition for which it was not prescribed. Do not give TIROSINT to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about TIROSINT that is written for health professionals.\n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the ingredients in TIROSINT?\n <br/>\n<br/>\n\t\t\tActive ingredient \n </span>: levothyroxine sodium\n <br/>\n<br/>\n<span class=\"Bold\">Inactive ingredients</span>: gelatin, glycerin, and water\n <br/>\n<br/>\n\t\t\tManufactured by: IBSA Institut Biochimique SA, 6912 Pazzallo, Switzerland;\n <br/>\n<br/>\n\t\t\tMarketed and distributed by: IBSA Pharma Inc., Parsippany, NJ 07054 USA\n <br/>\n<br/>\n\t\t\tFor more information, go to www.tirosint.com or call 1-800-587-3513.\n </td>\n</tr>\n</tbody>\n</table></div>" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0005-4

{ "type": "p", "children": [], "text": "NDC 71858-0005-4" }

13 mcg per capsule

{ "type": "p", "children": [], "text": "13 mcg\n \n\nper capsule\n " }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0010-4

{ "type": "p", "children": [], "text": "NDC 71858-0010-4" }

25 mcg per capsule

{ "type": "p", "children": [], "text": "25 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT ®\n \n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0012-4

{ "type": "p", "children": [], "text": "NDC 71858-0012-4" }

37.5 mcg per capsule

{ "type": "p", "children": [], "text": "37.5 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT ®\n \n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0013-4

{ "type": "p", "children": [], "text": "NDC 71858-0013-4" }

44 mcg per capsule

{ "type": "p", "children": [], "text": "44 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0015-4

{ "type": "p", "children": [], "text": "NDC 71858-0015-4" }

50 mcg per capsule

{ "type": "p", "children": [], "text": "50 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT ®\n \n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0017-4

{ "type": "p", "children": [], "text": "NDC 71858-0017-4" }

62.5 mcg per capsule

{ "type": "p", "children": [], "text": "62.5 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0020-4

{ "type": "p", "children": [], "text": "NDC 71858-0020-4" }

75 mcg per capsule

{ "type": "p", "children": [], "text": "75 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0025-4

{ "type": "p", "children": [], "text": "NDC 71858-0025-4" }

88 mcg per capsule

{ "type": "p", "children": [], "text": "88 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0030-4

{ "type": "p", "children": [], "text": "NDC 71858-0030-4" }

100 mcg per capsule

{ "type": "p", "children": [], "text": "100 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0035-4

{ "type": "p", "children": [], "text": "NDC 71858-0035-4" }

112 mcg per capsule

{ "type": "p", "children": [], "text": "112 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0040-4

{ "type": "p", "children": [], "text": "NDC 71858-0040-4" }

125 mcg per capsule

{ "type": "p", "children": [], "text": "125 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0045-4

{ "type": "p", "children": [], "text": "NDC 71858-0045-4" }

137 mcg per capsule

{ "type": "p", "children": [], "text": "137 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0050-4

{ "type": "p", "children": [], "text": "NDC 71858-0050-4" }

150 mcg per capsule

{ "type": "p", "children": [], "text": "150 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0055-4

{ "type": "p", "children": [], "text": "NDC 71858-0055-4" }

175 mcg per capsule

{ "type": "p", "children": [], "text": "175 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

TIROSINT ® (levothyroxine sodium) capsules

{ "type": "p", "children": [], "text": "TIROSINT \n ®\n\n\n(levothyroxine sodium) capsules\n " }

NDC 71858-0060-4

{ "type": "p", "children": [], "text": "NDC 71858-0060-4" }

200 mcg per capsule

{ "type": "p", "children": [], "text": "200 mcg per capsule" }

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

{ "type": "p", "children": [], "text": "Do not remove individual capsules from blister packaging until ready to use" }

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

{ "type": "p", "children": [], "text": "Swallow capsule whole. Do not cut, crush, or chew." }

R x Only 3 blisters x 10 capsules

{ "type": "p", "children": [], "text": "R \n x Only\n \n\n3 blisters x 10 capsules\n " }

IBSA

{ "type": "p", "children": [], "text": "IBSA" }

Hypothyroidism Levothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

{ "type": "p", "children": [], "text": "\nHypothyroidism\n\nLevothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.\n " }

Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression Levothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

{ "type": "p", "children": [], "text": "\nPituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression\n\nLevothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.\n " }

Limitations of Use

{ "type": "p", "children": [], "text": "\nLimitations of Use\n" }

{ "type": "ul", "children": [ "Levothyroxine sodium tablets are not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients as there are no clinical benefits and overtreatment with levothyroxine sodium tablets may induce hyperthyroidism \n [see \n Warnings and Precautions (5.1)]. \n \n", "Levothyroxine sodium tablets are not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis." ], "text": "" }

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 dosage adjustments when regularly administering within one hour of certain foods that may affect levothyroxine sodium tablets absorption [see Dosage and Administration (2.2 and 2.3), Drug Interactions (7.9) and Clinical Pharmacology (12.3)].

Administer levothyroxine sodium tablets to pediatric patients who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 to 10 mL) of water and immediately administering the suspension by spoon or dropper. Ensure the patient ingests the full amount of the suspension. 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)].

The dosage 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 dosage adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters [see Dosage and Administration (2.4)]. For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal [see Dosage and Administration (2.3)].

For secondary or tertiary hypothyroidism, serum TSH is not a reliable measure of levothyroxine sodium tablets dosage adequacy and should not be used to monitor therapy. Use the serum free-T4 level to titrate levothyroxine sodium tablets dosing until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range [see Dosage and Administration (2.3)].

Inquire whether patients are taking biotin or biotin-containing supplements. If so, advise them to stop biotin supplementation at least 2 days before assessing TSH and/or T4 levels [see Dosage and Administration (2.4) and Drug Interactions (7.10)].

The peak therapeutic effect of a given dose of levothyroxine sodium tablets may not be attained for 4 to 6 weeks.

Primary, Secondary, and Tertiary Hypothyroidism in Adults The recommended starting daily dosage of levothyroxine sodium tablets in adults with primary, secondary, or tertiary hypothyroidism is based on age and comorbid cardiac conditions, as described in Table 1. For patients at risk of atrial fibrillation or patients with underlying cardiac disease, start with a lower dosage and titrate the dosage more slowly to avoid exacerbation of cardiac symptoms. Dosage titration is based on serum TSH or free-T4 [see Dosage and Administration (2.2)].

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1. Levothyroxine Sodium Tablets Dosing Guidelines for Hypothyroidism in Adults <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></span> </caption> <colgroup> <col width="29%"/> <col width="34%"/> <col width="37%"/> </colgroup> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Dosages greater than 200 mcg/day are seldom required. An inadequate response to daily dosages greater than 300 mcg/day is rare and may indicate poor compliance, malabsorption, drug interactions, or a combination of these factors. [see Dosage and Administration (2.1) and Drug Interactions (7)].</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Patient Population</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Starting Dosage</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Dosage Titration Based on Serum TSH or Free-T4</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Adults diagnosed with hypothyroidism</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Full replacement dose is 1.6 mcg/kg/day. Some patients require a lower starting dose.</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed until the patient is euthyroid.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Adults at risk for atrial fibrillation or with underlying cardiac disease</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Lower starting dose (less than 1.6 mcg/kg/day)</p> </td><td class="Botrule Rrule" rowspan="2" valign="middle"> <p class="First">Titrate dosage every 6 to 8 weeks, as needed until the patient is euthyroid.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Geriatric patients</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Lower starting dose (less than 1.6 mcg/kg/day)</p> </td> </tr> </tbody> </table></div>

Primary, Secondary and Tertiary Hypothyroidism in Pediatric Patients The recommended starting daily dosage of levothyroxine sodium tablets in pediatric patients with primary, secondary, or tertiary hypothyroidism is based on body weight and changes with age as described in Table 2. Titrate the dosage (every 2 weeks) as needed based on serum TSH or free-T4 until the patient is euthyroid [see Dosage and Administration (2.2)].

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2. Levothyroxine Sodium Tablets Dosing Guidelines for Hypothyroidism in Pediatric Patients</span> </caption> <colgroup> <col width="51%"/> <col width="49%"/> </colgroup> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Adjust dosage based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4)].</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Age</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Starting Daily Dosage Per Kg Body Weight</span><a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0 to 3 months</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">10 to 15 mcg/kg/day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">3 to 6 months</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">8 to 10 mcg/kg/day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">6 to 12 months</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">6 to 8 mcg/kg/day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">1 to 5 years</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">5 to 6 mcg/kg/day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">6 to 12 years</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">4 to 5 mcg/kg/day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Greater than 12 years but growth and puberty incomplete</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2 to 3 mcg/kg/day</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Growth and puberty complete</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1.6 mcg/kg/day</p> </td> </tr> </tbody> </table></div>

Pediatric Patients from Birth to 3 Months of Age at Risk for Cardiac Failure. Start at a lower starting dosage and increase the dosage every 4 to 6 weeks as needed based on clinical and laboratory response.

Pediatric Patients at Risk for Hyperactivity To minimize the risk of hyperactivity, start at one-fourth the recommended full replacement dosage, and increase on a weekly basis by one-fourth the full recommended replacement dosage until the full recommended replacement dosage is reached.

Hypothyroidism in Pregnant Patients For pregnant patients with pre-existing hypothyroidism, measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In pregnant patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range.

The recommended daily dosage of levothyroxine sodium tablets in pregnant patients is described in Table 3.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3. Levothyroxine Sodium Tablets Dosing Guidelines for Hypothyroidism in Pregnant Patients</span> </caption> <colgroup> <col width="30%"/> <col width="34%"/> <col width="36%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Patient Population</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Starting Dosage</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Dose Adjustment and Titration</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pre-existing primary hypothyroidism with serum TSH above normal trimester- specific range</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Pre-pregnancy dosage may increase during pregnancy</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Increase levothyroxine sodium tablet dosage by 12.5 to 25 mcg per day. Monitor TSH every 4 weeks until a stable dose is reached and serum TSH is within normal trimester-specific range. Reduce levothyroxine sodium tablet dosage to pre-pregnancy levels immediately after delivery. Monitor serum TSH 4 to 8 weeks postpartum.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">New onset hypothyroidism (TSH ≥ 10 mIU per liter)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.6 mcg/kg/day</p> </td><td class="Botrule Rrule" rowspan="2" valign="top"> <p class="First">Monitor serum TSH every 4 weeks and adjust levothyroxine sodium tablet dosage until serum TSH is within normal trimester-specific range.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">New onset hypothyroidism (TSH &lt; 10 mIU per liter)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.0 mcg/kg/day</p> </td> </tr> </tbody> </table></div>

TSH Suppression in Well-differentiated Thyroid Cancer in Adult and Pediatric Patients The levothyroxine sodium tablets dosage is based on the target level of TSH suppression for the stage and clinical status of thyroid cancer.

Assess the adequacy of therapy by periodic assessment of laboratory tests and clinical evaluation.

Biotin supplementation may interfere with immunoassays for TSH, T4, and T3, resulting in erroneous thyroid hormone test results. Stop biotin and biotin-containing supplements for at least 2 days before assessing TSH and/or T4 levels [see Drug Interactions (7.10)].

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.

Adults In adult patients with primary hypothyroidism, monitor serum TSH levels after an interval of 6 to 8 weeks after any change in dosage. In patients on a stable and appropriate replacement dosage, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient's clinical status.

Pediatric Patients In patients with hypothyroidism, assess the adequacy of replacement therapy by measuring both serum TSH and total or free-T4. Monitor TSH and total or free-T4 in pediatric patients as follows: 2 and 4 weeks after the initiation of treatment, 2 weeks after any change in dosage, and then every 3 to 12 months thereafter following dosage stabilization until growth is completed. Poor compliance or abnormal values may necessitate more frequent monitoring. Perform routine clinical examination, including assessment of development, mental and physical growth, and bone maturation, at regular intervals.

The general aim of therapy is to normalize the serum TSH level. TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of levothyroxine sodium tablets therapy and/or of the serum TSH to decrease below 20 mIU per liter within 4 weeks may indicate the patient is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of levothyroxine sodium tablets [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].

Secondary and Tertiary Hypothyroidism Monitor serum free-T4 levels and maintain in the upper half of the normal range in these patients.

Levothyroxine sodium tablets USP are round, colored, scored and debossed with following debossing details on one side and break-line on other side. They are available as follows (Table 4):

{ "type": "p", "children": [], "text": "Levothyroxine sodium tablets USP are round, colored, scored and debossed with following debossing details on one side and break-line on other side. They are available as follows (Table 4):" }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4: Levothyroxine Sodium Tablet Strengths and Identifying Features</span> </caption> <colgroup> <col width="30%"/> <col width="36%"/> <col width="33%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Tablet Strength</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Tablet Color/Shape</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Debossing Details</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">25 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Peach/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L15</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">50 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">White/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L16</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">75 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Violet/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L17</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">88 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Olive/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L19</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">100 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Yellow/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L20</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">112 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Rose/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L21</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">125 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Tan/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L22</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">137 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Turquoise/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L23</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">150 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Blue/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L24</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">175 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Lilac/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L25</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">200 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Pink/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L26</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">300 mcg</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Green/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L27</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 4: Levothyroxine Sodium Tablet Strengths and Identifying Features</span>\n</caption>\n<colgroup>\n<col width=\"30%\"/>\n<col width=\"36%\"/>\n<col width=\"33%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Tablet Strength</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Tablet Color/Shape</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Debossing Details</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">25 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Peach/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L15</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">50 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">White/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L16</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">75 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Violet/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L17</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">88 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Olive/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L19</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">100 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Yellow/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L20</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">112 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Rose/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L21</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">125 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Tan/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L22</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">137 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Turquoise/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L23</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">150 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Blue/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L24</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">175 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Lilac/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L25</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">200 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Pink/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L26</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">300 mcg</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Green/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L27</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

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

{ "type": "p", "children": [], "text": "Levothyroxine sodium tablets are contraindicated in patients with uncorrected adrenal insufficiency \n [see \n Warnings and Precautions (5.4)]. \n \n" }

Levothyroxine sodium tablet has a narrow therapeutic index. Overtreatment or undertreatment with Levothyroxine sodium tablets may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, gastrointestinal function, and glucose and lipid metabolism in adult or pediatric patients.

In pediatric patients with congenital and acquired hypothyroidism, undertreatment may adversely affect cognitive development and linear growth, and overtreatment is associated with craniosynostosis and acceleration of bone age [see Use in Specific Populations (8.4)].

Titrate the dose of Levothyroxine sodium tablets carefully and monitor response to titration to avoid these effects [see Dosage and Administration (2.4)]. Consider the potential for food or drug interactions and adjust the administration or dosage of Levothyroxine sodium tablets as needed [see Dosage and Administration (2.1), Drug Interactions (7.1), and Clinical Pharmacology (12.3)].

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.

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.

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)].

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)].

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.

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:

{ "type": "p", "children": [], "text": "Adverse reactions associated with levothyroxine sodium tablets therapy are primarily those of hyperthyroidism due to therapeutic overdosage \n [see \n Warnings and Precautions (5), \n Overdosage (10)]. \n They include the following:\n " }

{ "type": "ul", "children": [ "\nGeneral: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating\n ", "\nCentral nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia\n ", "\nMusculoskeletal: tremors, muscle weakness, muscle spasm\n ", "\nCardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest\n ", "\nRespiratory: dyspnea\n ", "\nGastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests\n ", "\nDermatologic: hair loss, flushing, rash\n ", "\nEndocrine: decreased bone mineral density\n ", "\nReproductive: menstrual irregularities, impaired fertility\n " ], "text": "" }

Seizures have been reported rarely with the institution of levothyroxine therapy.

{ "type": "p", "children": [], "text": "Seizures have been reported rarely with the institution of levothyroxine therapy." }

Adverse Reactions in Pediatric Patients Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants who have not undergone complete closure of the fontanelles, and in premature closure of the epiphyses in pediatric patients still experiencing growth with resultant compromised adult height.

{ "type": "p", "children": [], "text": "\nAdverse Reactions in Pediatric Patients\n\nPseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants who have not undergone complete closure of the fontanelles, and in premature closure of the epiphyses in pediatric patients still experiencing growth with resultant compromised adult height.\n " }

Hypersensitivity Reactions Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\n\nHypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.\n " }

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 (Tables 5 to 8).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 5. Drugs That May Decrease T4 Absorption (Hypothyroidism)</span> </caption> <colgroup> <col width="38%"/> <col width="62%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First">Potential impact: Concurrent use may reduce the efficacy of levothyroxine sodium tablets by binding and delaying or preventing absorption, potentially resulting in hypothyroidism.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Phosphate Binders</p> <p>(e.g., calcium carbonate, ferrous sulfate, sevelamer, lanthanum)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Phosphate binders may bind to levothyroxine. Administer levothyroxine sodium tablets at least 4 hours apart from these agents.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Orlistat</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Monitor patients treated concomitantly with orlistat and levothyroxine sodium tablets for changes in thyroid function.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Bile Acid Sequestrants</p> <p>(e.g., colesevelam, cholestyramine, colestipol)</p> <p>Ion Exchange Resins</p> <p>(e.g., Kayexalate)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer levothyroxine sodium tablets at least 4 hours prior to these drugs or monitor TSH levels.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Proton Pump Inhibitors</p> <p>Sucralfate</p> <p>Antacids</p> <p>(e.g., aluminum &amp; magnesium hydroxides, simethicone)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Gastric acidity is an essential requirement for adequate absorption of levothyroxine. Sucralfate, antacids and proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce levothyroxine absorption. Monitor patients appropriately.</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 6. Drugs That May Alter T4 and Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism)</span> </caption> <colgroup> <col width="38%"/> <col width="62%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clofibrate</p> <p>Estrogen-containing oral contraceptives</p> <p>Estrogens (oral)</p> <p>Heroin / Methadone</p> <p>5-Fluorouracil</p> <p>Mitotane</p> <p>Tamoxifen</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">These drugs may increase serum thyroxine-binding globulin (TBG) concentration.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Androgens / Anabolic Steroids</p> <p>Asparaginase</p> <p>Glucocorticoids</p> <p>Slow-Release Nicotinic Acid</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">These drugs may decrease serum TBG concentration.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Potential impact (below): Administration of these agents with levothyroxine sodium tablets results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Salicylates (&gt; 2 g/day)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4 is followed by return of FT4 to normal levels with sustained therapeutic serum salicylate concentrations, although total T4 levels may decrease by as much as 30%.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Other drugs:</p> <p>Carbamazepine</p> <p>Furosemide (&gt; 80 mg IV)</p> <p>Heparin</p> <p>Hydantoins</p> <p>Non-Steroidal Anti-inflammatory Drugs</p> <p>-Fenamates</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">These drugs may cause protein-binding site displacement. Furosemide has been shown to inhibit the protein binding of T4 to TBG and albumin, causing an increase free T4 fraction in serum. Furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower the total T4 level. Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total and free T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Closely monitor thyroid hormone parameters.</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 7. Drugs That May Alter Hepatic Metabolism of T4 (Hypothyroidism)</span> </caption> <colgroup> <col width="38%"/> <col width="62%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First">Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine sodium tablets requirements.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Phenobarbital</p> <p>Rifampin</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Phenobarbital has been shown to reduce the response to thyroxine. Phenobarbital increases L-thyroxine metabolism by inducing uridine 5'-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Rifampin has been shown to accelerate the metabolism of levothyroxine.</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 8. Drugs That May Decrease Conversion of T4 to T3</span> </caption> <colgroup> <col width="38%"/> <col width="62%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First">Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T4 to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Drug or Drug Class</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">Effect</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Beta-adrenergic antagonists (e.g., Propranolol &gt; 160 mg/day)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">In patients treated with large doses of propranolol (&gt; 160 mg/day), T3 and T4 levels change, TSH levels remain normal, and patients are clinically euthyroid. Actions of particular beta-adrenergic antagonists may be impaired when a hypothyroid patient is converted to the euthyroid state.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Glucocorticoids (e.g., Dexamethasone ≥ 4 mg/day)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels. However, long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (See above).</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Other drugs:</p> <p>Amiodarone</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, and decreased or normal free-T3) in clinically euthyroid patients.</p> </td> </tr> </tbody> </table></div>

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 tablet 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 levothyroxine sodium tablets dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

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.

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.

Concurrent use of ketamine and levothyroxine sodium tablets may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients.

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.

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

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.

Thyroxine-binding Globulin (TBG) 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.

Biotin Biotin supplementation is known to interfere with thyroid hormone immunoassays that are based on a biotin and streptavidin interaction, which may result in erroneous thyroid hormone test results. Stop biotin and biotin-containing supplements for at least 2 days prior to thyroid testing.

Risk Summary The clinical experience, including data from postmarketing studies, in pregnant women treated with oral levothyroxine to maintain euthyroid state have not reported increased rates of major birth defects, miscarriages, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated hypothyroidism in pregnancy. Since TSH levels may increase during pregnancy, TSH should be monitored and levothyroxine sodium tablets dosage adjusted during pregnancy ( see Clinical Considerations). Animal reproductive studies have not been conducted with levothyroxine sodium. Levothyroxine sodium tablets should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Maternal hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, and premature delivery. Untreated maternal hypothyroidism may have an adverse effect on fetal neurocognitive development.

Dose Adjustments During Pregnancy and the Postpartum Period Pregnancy may increase levothyroxine sodium tablets requirements. Serum TSH levels should be monitored and the levothyroxine sodium tablets dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the levothyroxine sodium tablets dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3)].

Risk Summary Published studies report that levothyroxine is present in human milk following the administration of oral levothyroxine. No adverse effects on the breastfed infant have been reported and there is no information on the effects of levothyroxine on milk production. Adequate levothyroxine treatment during lactation may normalize milk production in hypothyroid lactating mothers with low milk supply. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for levothyroxine sodium tablets and any potential adverse effects on the breastfed infant from levothyroxine sodium tablets or from the underlying maternal condition.

Levothyroxine Sodium Tablets is indicated in patients from birth to less than 17 years of age:

Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism on cognitive development as well as on overall physical growth and maturation. Therefore, initiate levothyroxine sodium tablets therapy immediately upon diagnosis. Levothyroxine is generally continued for life in these patients. [see Warnings and Precautions (5.1)].

Closely monitor infants during the first 2 weeks of levothyroxine sodium tablets therapy for cardiac overload and arrhythmias.

Because of the increased prevalence of cardiovascular disease among the elderly, initiate levothyroxine sodium tablets at less than the full replacement dose [see Dosage and Administration (2.3) and Warnings and Precautions (5.2)]. Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with levothyroxine overtreatment in the elderly.

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.

{ "type": "p", "children": [], "text": "The signs and symptoms of overdosage are those of hyperthyroidism \n [see \n Warnings and Precautions (5) and \n Adverse Reactions (6)]. \n 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.\n " }

Reduce the levothyroxine sodium tablets dosage or discontinue temporarily if signs or symptoms of overdosage occur. Initiate appropriate supportive treatment as dictated by the patient's medical status.

{ "type": "p", "children": [], "text": "Reduce the levothyroxine sodium tablets dosage 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.

{ "type": "p", "children": [], "text": "For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or \n www.poison.org.\n " }

Levothyroxine sodium tablets USP is L-thyroxine (T4) and contains synthetic crystalline L-3,3',5,5' tetraiodothyronine sodium salt. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C 15H 10I 4N NaO 4xH 2O, molecular weight of 798.85 (anhydrous), and structural formula as shown:

{ "type": "p", "children": [], "text": "Levothyroxine sodium tablets USP is L-thyroxine (T4) and contains synthetic crystalline L-3,3',5,5' tetraiodothyronine sodium salt. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C\n 15H\n 10I\n 4N NaO\n 4xH\n 2O, molecular weight of 798.85 (anhydrous), and structural formula as shown:\n " }

Levothyroxine sodium tablets USP 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, 200 mcg, and 300 mcg. Each levothyroxine sodium tablets USP contains the inactive ingredients corn starch, croscarmellose sodium, magnesium stearate, mannitol and sodium bicarbonate. Table 9 provides a listing of the color additives by tablet strength:

{ "type": "p", "children": [], "text": "Levothyroxine sodium tablets USP 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, 200 mcg, and 300 mcg. Each levothyroxine sodium tablets USP contains the inactive ingredients corn starch, croscarmellose sodium, magnesium stearate, mannitol and sodium bicarbonate. Table 9 provides a listing of the color additives by tablet strength:" }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 9. Levothyroxine Sodium Tablets USP Color Additives</span> </caption> <colgroup> <col width="20%"/> <col width="80%"/> </colgroup> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>Note – FD&amp;C Yellow No. 6 Aluminum Lake is peach in color.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Strength (mcg)</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Color additive(s)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">25</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Yellow No. 6 Aluminum Lake <a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">50</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Blue 1 Aluminum Lake</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">75</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Red No. 40 Aluminum Lake, FD&amp;C Blue No. 2 Aluminum Lake</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">88</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Yellow No. 6 Aluminum Lake <a class="Sup" href="#footnote-3">*</a>, FD&amp;C Blue No. 1 Aluminum Lake, D&amp;C Yellow No. 10 Aluminum Lake </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">100</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Yellow No. 6 Aluminum Lake <a class="Sup" href="#footnote-3">*</a>, D&amp;C Yellow No. 10 Aluminum Lake </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">112</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">D&amp;C Red No. 27 Aluminum Lake</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">125</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Yellow No. 6 Aluminum Lake <a class="Sup" href="#footnote-3">*</a>, FD&amp;C Blue No. 1 Aluminum Lake, FD&amp;C Red No. 40 Aluminum Lake, FD&amp;C Blue No. 2 Aluminum Lake </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">137</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Blue No. 1 Aluminum Lake</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">150</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Blue No. 2 Aluminum Lake</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">175</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Blue No. 1 Aluminum Lake, D&amp;C Red No. 27 Aluminum Lake</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">200</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Red No. 40 Aluminum Lake</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">300</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">FD&amp;C Yellow No. 6 Aluminum Lake <a class="Sup" href="#footnote-3">*</a>, FD&amp;C Blue No. 1 Aluminum Lake, D&amp;C Yellow No. 10 Aluminum Lake </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 9. Levothyroxine Sodium Tablets USP Color Additives</span>\n</caption>\n<colgroup>\n<col width=\"20%\"/>\n<col width=\"80%\"/>\n</colgroup>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"2\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">*</a>\n</dt>\n<dd>Note – FD&amp;C Yellow No. 6 Aluminum Lake is peach in color.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Strength (mcg)</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Color additive(s)</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">25</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Yellow No. 6 Aluminum Lake\n <a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">*</a>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">50</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Blue 1 Aluminum Lake</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">75</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Red No. 40 Aluminum Lake, FD&amp;C Blue No. 2 Aluminum Lake</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">88</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Yellow No. 6 Aluminum Lake\n <a class=\"Sup\" href=\"#footnote-3\">*</a>, FD&amp;C Blue No. 1 Aluminum Lake, D&amp;C Yellow No. 10 Aluminum Lake\n </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">100</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Yellow No. 6 Aluminum Lake\n <a class=\"Sup\" href=\"#footnote-3\">*</a>, D&amp;C Yellow No. 10 Aluminum Lake\n </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">112</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">D&amp;C Red No. 27 Aluminum Lake</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">125</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Yellow No. 6 Aluminum Lake\n <a class=\"Sup\" href=\"#footnote-3\">*</a>, FD&amp;C Blue No. 1 Aluminum Lake, FD&amp;C Red No. 40 Aluminum Lake, FD&amp;C Blue No. 2 Aluminum Lake\n </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">137</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Blue No. 1 Aluminum Lake</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">150</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Blue No. 2 Aluminum Lake</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">175</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Blue No. 1 Aluminum Lake, D&amp;C Red No. 27 Aluminum Lake</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">200</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Red No. 40 Aluminum Lake</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">300</p>\n</td><td class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">FD&amp;C Yellow No. 6 Aluminum Lake\n <a class=\"Sup\" href=\"#footnote-3\">*</a>, FD&amp;C Blue No. 1 Aluminum Lake, D&amp;C Yellow No. 10 Aluminum Lake\n </p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Levothyroxine sodium tablet USP meets USP Dissolution Test 2.

{ "type": "p", "children": [], "text": "Levothyroxine sodium tablet USP meets USP Dissolution Test 2." }

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.

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.

Absorption Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80%. The majority of the levothyroxine sodium tablets dose is absorbed from the jejunum and upper ileum. The relative bioavailability of levothyroxine sodium tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 93%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption [see Drug Interactions (7)].

Distribution Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [see Drug Interactions (7)]. Thyroid hormones do not readily cross the placental barrier [see Use in Specific Populations (8.1)].

Elimination Metabolism T4 is slowly eliminated (see Table 10). The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and rT3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.

Excretion Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 10. Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients</span> </caption> <colgroup> <col width="20%"/> <col width="23%"/> <col width="18%"/> <col width="18%"/> <col width="22%"/> </colgroup> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>Includes TBG, TBPA, and TBA</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">†</a> </dt> <dd>3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hormone</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Ratio in Thyroglobulin</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Biologic Potency</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">t <span class="Sub">1/2</span>(days) </span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Protein Binding (%)</span><a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Levothyroxine (T4)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">10 to 20</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">6 to 7 <a class="Sup" href="#footnote-5" name="footnote-reference-5">†</a> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">99.96</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Liothyronine (T3)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">≤ 2</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">99.5</p> </td> </tr> </tbody> </table></div>

Long-term carcinogenicity studies in animals to evaluate the carcinogenic potential of levothyroxine have not been performed. Studies to evaluate mutagenic potential and animal fertility have not been performed.

How Supplied Levothyroxine sodium tablets USP are round, colored, scored and debossed with following debossing details on one side and break-line on other side. They are supplied as follows:

{ "type": "p", "children": [], "text": "\nHow Supplied\n\nLevothyroxine sodium tablets USP are round, colored, scored and debossed with following debossing details on one side and break-line on other side. They are supplied as follows:\n " }

<div class="scrollingtable"><table width="100%"> <colgroup> <col width="14%"/> <col width="19%"/> <col width="14%"/> <col width="52%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Strength (mcg)</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Color/Shape</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Debossing Details</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Supplied as:</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">25</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Peach/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L15</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-453-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">50</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">White/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L16</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-464-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">75</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Violet/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L17</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-475-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">88</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Olive/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L19</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-486-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">100</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Yellow/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L20</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-497-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">112</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Rose/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L21</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-508-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">125</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Tan/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L22</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-519-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">137</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Turquoise/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L23</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-563-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">150</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Blue/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L24</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-530-01</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">175</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Lilac/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L25</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-541-01</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">200</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Pink/Round</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">L26</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Unit dose packages of 100 (10 x 10) NDC 60687-552-01</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<colgroup>\n<col width=\"14%\"/>\n<col width=\"19%\"/>\n<col width=\"14%\"/>\n<col width=\"52%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Strength (mcg)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Color/Shape</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Debossing Details</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Supplied as:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">25</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Peach/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L15</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-453-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">50</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">White/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L16</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-464-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">75</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Violet/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L17</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-475-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">88</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Olive/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L19</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-486-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">100</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Yellow/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L20</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-497-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">112</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Rose/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L21</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-508-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">125</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Tan/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L22</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-519-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">137</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Turquoise/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L23</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-563-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">150</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Blue/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L24</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-530-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">175</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Lilac/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L25</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-541-01</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">200</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Pink/Round</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">L26</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\">\n<p class=\"First\">Unit dose packages of 100 (10 x 10) NDC 60687-552-01</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

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

{ "type": "p", "children": [], "text": "\nStorage and Handling\n\nStore at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Levothyroxine sodium tablets USP should be protected from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

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

{ "type": "p", "children": [], "text": "Inform the patient of the following information to aid in the safe and effective use of Levothyroxine Sodium Tablets:" }

Dosing and Administration

{ "type": "p", "children": [], "text": "\nDosing and Administration\n" }

{ "type": "ul", "children": [ "Instruct patients to take levothyroxine sodium tablets only as directed by their healthcare provider.", "Instruct patients to take levothyroxine sodium tablets as a single dose, preferably on an empty stomach, one-half to one hour before breakfast.", "Inform patients that agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine. Instruct patients not to take levothyroxine sodium tablets within 4 hours of these agents.", "Instruct patients to notify their healthcare provider if they are pregnant or breastfeeding or are thinking of becoming pregnant while taking levothyroxine sodium tablets." ], "text": "" }

Important Information

{ "type": "p", "children": [], "text": "\nImportant Information\n" }

{ "type": "ul", "children": [ "Inform patients that it may take several weeks before they notice an improvement in symptoms.", "Inform patients that the levothyroxine in levothyroxine sodium tablet is intended to replace a hormone that is normally produced by the thyroid gland. Generally, replacement therapy is to be taken for life.", "Inform patients that levothyroxine sodium tablets should not be used as a primary or adjunctive therapy in a weight control program.", "Instruct patients to notify their healthcare provider if they are taking any other medications, including prescription and over-the-counter preparations.", "Instruct patients to discontinue biotin or any biotin-containing supplements for at least 2 days before thyroid function testing is conducted.", "Instruct patients to notify their physician of any other medical conditions they may have, particularly heart disease, diabetes, clotting disorders, and adrenal or pituitary gland problems, as the dose of medications used to control these other conditions may need to be adjusted while they are taking levothyroxine sodium tablets. If they have diabetes, instruct patients to monitor their blood and/or urinary glucose levels as directed by their physician and immediately report any changes to their physician. If patients are taking anticoagulants, their clotting status should be checked frequently.", "Instruct patients to notify their physician or dentist that they are taking levothyroxine sodium tablets prior to any surgery." ], "text": "" }

Adverse Reactions

{ "type": "p", "children": [], "text": "\nAdverse Reactions\n" }

{ "type": "ul", "children": [ "Instruct patients to notify their healthcare provider if they experience any of the following symptoms: rapid or irregular heartbeat, chest pain, shortness of breath, leg cramps, headache, nervousness, irritability, sleeplessness, tremors, change in appetite, weight gain or loss, vomiting, diarrhea, excessive sweating, heat intolerance, fever, changes in menstrual periods, hives or skin rash, or any other unusual medical event.", "Inform patients that partial hair loss may occur rarely during the first few months of levothyroxine sodium tablets therapy, but this is usually temporary." ], "text": "" }

LUPIN and the are registered trademarks of Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "LUPIN and the \n are registered trademarks of Lupin Pharmaceuticals, Inc.\n " }

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Lupin Pharmaceuticals, Inc. as follows:

{ "type": "p", "children": [], "text": "American Health Packaging unit dose blisters (see \n How Supplied section) contain drug product from Lupin Pharmaceuticals, Inc. as follows:\n " }

(25 mcg / 100 UD) NDC 60687-453-01 packaged from NDC 68180-965 (50 mcg / 100 UD) NDC 60687-464-01 packaged from NDC 68180-966 (75 mcg / 100 UD) NDC 60687-475-01 packaged from NDC 68180-967 (88 mcg / 100 UD) NDC 60687-486-01 packaged from NDC 68180-968 (100 mcg / 100 UD) NDC 60687-497-01 packaged from NDC 68180-969 (112 mcg / 100 UD) NDC 60687-508-01 packaged from NDC 68180-970 (125 mcg / 100 UD) NDC 60687-519-01 packaged from NDC 68180-971 (137 mcg / 100 UD) NDC 60687-563-01 packaged from NDC 68180-972 (150 mcg / 100 UD) NDC 60687-530-01 packaged from NDC 68180-973 (175 mcg / 100 UD) NDC 60687-541-01 packaged from NDC 68180-974 (200 mcg / 100 UD) NDC 60687-552-01 packaged from NDC 68180-975

{ "type": "p", "children": [], "text": "(25 mcg / 100 UD) NDC 60687-453-01 packaged from NDC 68180-965\n \n(50 mcg / 100 UD) NDC 60687-464-01 packaged from NDC 68180-966\n \n(75 mcg / 100 UD) NDC 60687-475-01 packaged from NDC 68180-967\n \n(88 mcg / 100 UD) NDC 60687-486-01 packaged from NDC 68180-968\n \n(100 mcg / 100 UD) NDC 60687-497-01 packaged from NDC 68180-969\n \n(112 mcg / 100 UD) NDC 60687-508-01 packaged from NDC 68180-970\n \n(125 mcg / 100 UD) NDC 60687-519-01 packaged from NDC 68180-971\n \n(137 mcg / 100 UD) NDC 60687-563-01 packaged from NDC 68180-972\n \n(150 mcg / 100 UD) NDC 60687-530-01 packaged from NDC 68180-973\n \n(175 mcg / 100 UD) NDC 60687-541-01 packaged from NDC 68180-974\n \n(200 mcg / 100 UD) NDC 60687-552-01 packaged from NDC 68180-975\n " }

Distributed by: American Health Packaging Columbus, OH 43217

{ "type": "p", "children": [], "text": "Distributed by:\n \nAmerican Health Packaging\n\nColumbus, OH 43217\n " }

8445301/0125(F)

{ "type": "p", "children": [], "text": "\n8445301/0125(F)\n" }

NDC 60687- 453-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 453-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

25 mcg (0.025 mg)

{ "type": "p", "children": [], "text": "\n25 mcg (0.025 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP..................................25 mcg (0.025 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP..................................25 mcg (0.025 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-965, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-965, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

745301 0445301/0524

{ "type": "p", "children": [], "text": "745301\n \n0445301/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

25 mcg (0.025 mg)

{ "type": "p", "children": [], "text": "\n25 mcg\n\n(0.025 mg)\n" }

NDC 60687- 464-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 464-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

50 mcg (0.05 mg)

{ "type": "p", "children": [], "text": "\n50 mcg (0.05 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP....................................50 mcg (0.05 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP....................................50 mcg (0.05 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-966, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-966, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

746401 0446401/0524

{ "type": "p", "children": [], "text": "746401\n \n0446401/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

50 mcg (0.05 mg)

{ "type": "p", "children": [], "text": "\n50 mcg\n\n(0.05 mg)\n" }

NDC 60687- 475-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 475-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

75 mcg (0.075 mg)

{ "type": "p", "children": [], "text": "\n75 mcg (0.075 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP..................................75 mcg (0.075 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP..................................75 mcg (0.075 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-967, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-967, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

747501 0447501/0524

{ "type": "p", "children": [], "text": "747501\n \n0447501/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

75 mcg (0.075 mg)

{ "type": "p", "children": [], "text": "\n75 mcg\n\n(0.075 mg)\n" }

NDC 60687- 486-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 486-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

88 mcg (0.088 mg)

{ "type": "p", "children": [], "text": "\n88 mcg (0.088 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP................................. 88 mcg (0.088 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP................................. 88 mcg (0.088 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-968, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-968, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

748601 0448601/0524

{ "type": "p", "children": [], "text": "748601\n \n0448601/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

88 mcg (0.088 mg)

{ "type": "p", "children": [], "text": "\n88 mcg\n\n(0.088 mg)\n" }

NDC 60687- 497-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 497-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

100 mcg (0.1 mg)

{ "type": "p", "children": [], "text": "\n100 mcg (0.1 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP....................................100 mcg (0.1 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP....................................100 mcg (0.1 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-969, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-969, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

749702 0449701/0524

{ "type": "p", "children": [], "text": "749702\n \n0449701/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

100 mcg (0.1 mg)

{ "type": "p", "children": [], "text": "\n100 mcg\n\n(0.1 mg)\n" }

NDC 60687- 508-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 508-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

112 mcg (0.112 mg)

{ "type": "p", "children": [], "text": "\n112 mcg (0.112 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP.................................112 mcg (0.112 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP.................................112 mcg (0.112 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-970, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-970, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

750802 0450801/0524

{ "type": "p", "children": [], "text": "750802\n \n0450801/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

112 mcg (0.112 mg)

{ "type": "p", "children": [], "text": "\n112 mcg\n\n(0.112 mg)\n" }

NDC 60687- 519-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 519-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

125 mcg (0.125 mg)

{ "type": "p", "children": [], "text": "\n125 mcg (0.125 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP................................125 mcg (0.125 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP................................125 mcg (0.125 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-971, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-971, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

751901 0451901/0524

{ "type": "p", "children": [], "text": "751901\n \n0451901/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

125 mcg (0.125 mg)

{ "type": "p", "children": [], "text": "\n125 mcg\n\n(0.125 mg)\n" }

NDC 60687- 563-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 563-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

137 mcg (0.137 mg)

{ "type": "p", "children": [], "text": "\n137 mcg (0.137 mg)\n" }

100 Tablets (10 x 10)               Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)               Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP................................ 137 mcg (0.137 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP................................ 137 mcg (0.137 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-972, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-972, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

756301 0456301/0524

{ "type": "p", "children": [], "text": "756301\n \n0456301/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

137 mcg (0.137 mg)

{ "type": "p", "children": [], "text": "\n137 mcg\n\n(0.137 mg)\n" }

NDC 60687- 530-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 530-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

150 mcg (0.15 mg)

{ "type": "p", "children": [], "text": "\n150 mcg (0.15 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP..................................150 mcg (0.15 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP..................................150 mcg (0.15 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-973, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-973, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

753001 0453001/0524

{ "type": "p", "children": [], "text": "753001\n \n0453001/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

150 mcg (0.15 mg)

{ "type": "p", "children": [], "text": "\n150 mcg\n\n(0.15 mg)\n" }

NDC 60687- 541-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 541-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

175 mcg (0.175 mg)

{ "type": "p", "children": [], "text": "\n175 mcg (0.175 mg)\n" }

100 Tablets (10 x 10)              Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)              Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP................................ 175 mcg (0.175 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP................................ 175 mcg (0.175 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-974, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-974, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

754101 0454101/0524

{ "type": "p", "children": [], "text": "754101\n \n0454101/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

175 mcg (0.175 mg)

{ "type": "p", "children": [], "text": "\n175 mcg\n\n(0.175 mg)\n" }

NDC 60687- 552-01

{ "type": "p", "children": [], "text": "NDC 60687-\n 552-01\n " }

Levothyroxine Sodium Tablets USP

{ "type": "p", "children": [], "text": "\nLevothyroxine Sodium\n\nTablets USP\n " }

200 mcg (0.2 mg)

{ "type": "p", "children": [], "text": "\n200 mcg (0.2 mg)\n" }

100 Tablets (10 x 10)               Rx Only

{ "type": "p", "children": [], "text": "\n100 Tablets (10 x 10)               Rx Only\n" }

Each Tablet Contains: Levothyroxine Sodium USP................................... 200 mcg (0.2 mg)

{ "type": "p", "children": [], "text": "\nEach Tablet Contains:\n\nLevothyroxine Sodium USP................................... 200 mcg (0.2 mg)\n " }

Usual Dosage: See full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Dosage: See full prescribing information.\n " }

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted between\n \n15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].\n \nProtect from light and moisture.\n " }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn or broken.\n " }

The drug product contained in this package is from NDC # 68180-975, Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 68180-975, Lupin Pharmaceuticals, Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus, Ohio 43217" }

755201 0455201/0524

{ "type": "p", "children": [], "text": "755201\n \n0455201/0524\n " }

Levothyroxine Sodium Tablet USP

{ "type": "p", "children": [], "text": "Levothyroxine \n Sodium Tablet USP\n " }

200 mcg (0.2 mg)

{ "type": "p", "children": [], "text": "\n200 mcg\n\n(0.2 mg)\n" }