FDA

Levothyroxine Sodium

Approved 21 Dec 2022OralTablet

The FDA lists this product in 60 strengths and forms.

Indications

Hypothyroidism Levothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression Levothyroxine sodium tablets are indicated in adult and pediatric patients, including neonates, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

Limitations of Use Levothyroxine sodium tablets are not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients as there are no clinical benefits and overtreatment with levothyroxine sodium tablets may induce hyperthyroidism [see Warnings and Precautions ( 5.1 )]. Levothyroxine sodium tablets are not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.

Levothyroxine sodium tablets are a L-thyroxine (T4) indicated in adult and pediatric patients, including neonates, for: Hypothyroidism: As replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. ( 1 ) Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression: As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

( 1 ) Limitations of Use: Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients Not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis

Contraindications

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

Warnings and precautions

Serious risks related to overtreatment or undertreatment with levothyroxine sodium: Titrate the dose of levothyroxine sodium carefully and monitor response to titration. ( 5.1 ) Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate levothyroxine sodium at less than the full replacement dose because of the increased risk of cardiac adverse reactions, including atrial fibrillation.

( 2.3 , 5.2 , 8.5 ) Myxedema coma: Do not use oral thyroid hormone drug products to treat myxedema coma. ( 5.3 ) Acute adrenal crisis in patients with concomitant adrenal insufficiency: Treat with replacement glucocorticoids prior to initiation of levothyroxine sodium treatment. ( 5.4 ) Worsening of diabetic control: Therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements.

At a glance

Brand name: Levothyroxine Sodium
Route: Oral
Dosage form: Tablet
Applicant: Macleods Pharms LTD
Status: Prescription
FDA approval: 21 Dec 2022
Application: ANDA211417-010

Indications

Warnings and precautions

Interactions

See full prescribing information for drugs that affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to levothyroxine sodium. ( 7 )

7.1Drugs Known to Affect Thyroid Hormone Pharmacokinetics

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

Drug or Drug Class Effect Phosphate Binders (e.g., calcium carbonate, ferrous sulfate, sevelamer, lanthanum) Phosphate binders may bind to levothyroxine. Administer levothyroxine sodium tablets at least 4 hours apart from these agents. Orlistat Monitor patients treated concomitantly with orlistat and levothyroxine sodium for changes in thyroid function. Bile Acid Sequestrants (e.g., colesevelam, cholestyramine, colestipol) Ion Exchange Resins (e.g., Kayexalate) 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. Proton Pump Inhibitors Sucralfate Antacids (e.g., aluminum & magnesium hydroxides, simethicone) 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.

Table 6. Drugs That May Alter T4 and Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism) Drug or Drug Class Effect Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin / Methadone 5-Fluorouracil Mitotane Tamoxifen These drugs may increase serum thyroxine-binding globulin (TBG) concentration. Androgens / Anabolic Steroids Asparaginase Glucocorticoids Slow-Release Nicotinic Acid These drugs may decrease serum TBG concentration.

Potential impact (below): Administration of these agents with levothyroxine sodium results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations. Salicylates (> 2 g/day) 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%.

Other drugs: Carbamazepine Furosemide (> 80 mg IV) Heparin Hydantoins Non-Steroidal Anti-inflammatory Drugs - Fenamates 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. Table 7. Drugs That May Alter Hepatic Metabolism of T4 (Hypothyroidism) Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine sodium requirements.

Drug or Drug Class Effect Phenobarbital Rifampin 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.

Table 8. Drugs That May Decrease Conversion of T4 to T3 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. Drug or Drug Class Effect Beta-adrenergic antagonists (e.g., Propranolol > 160 mg/day) In patients treated with large doses of propranolol (> 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. Glucocorticoids (e.g., Dexamethasone ≥ 4 mg/day) 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).

Other drugs: Amiodarone 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.

7.2Antidiabetic Therapy Addition

of levothyroxine sodium 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 )].

7.3Oral Anticoagulants

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

7.4Digitalis Glycosides

Levothyroxine sodium 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.

7.5Antidepressant Therapy

Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and levothyroxine sodium 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 may accelerate the onset of action of tricyclics.

Administration of sertraline in patients stabilized on levothyroxine sodium may result in increased levothyroxine sodium requirements.

7.6Ketamine

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

7.7Sympathomimetics

Concurrent use of sympathomimetics and levothyroxine sodium 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.

7.8Tyrosine-Kinase Inhibitors

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

7.9Drug-Food Interactions Consumption

of certain foods may affect levothyroxine sodium 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 absorp

Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA

Adverse reactions

Adverse reactions associated with levothyroxine sodium therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions ( 5 ) and Overdosage ( 10 )]. They include the following: General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia Musculoskeletal: tremors, muscle weakness, muscle spasm Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest Respiratory: dyspnea Gastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests Dermatologic: hair loss, flushing, rash Endocrine: decreased bone mineral density Reproductive: menstrual irregularities, impaired fertility Seizures 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. 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. Adverse reactions associated with levothyroxine sodium therapy are primarily those of hyperthyroidism due to therapeutic overdosage: arrhythmias, myocardial infarction, dyspnea, muscle spasm, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Levothyroxine Sodium

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Levothyroxine Sodium

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Serious Risks Related to Overtreatment or Undertreatment with Levothyroxine Sodium

5.3Myxedema Coma

5.4Acute Adrenal Crisis in Patients with Concomitant Adrenal Insufficiency

5.5Worsening of Diabetic Control Addition

5.6Decreased Bone Mineral Density Associated with Thyroid Hormone Over-Replacement

Interactions

7.1Drugs Known to Affect Thyroid Hormone Pharmacokinetics

7.2Antidiabetic Therapy Addition

7.3Oral Anticoagulants

7.4Digitalis Glycosides

7.5Antidepressant Therapy

7.6Ketamine

7.7Sympathomimetics

7.8Tyrosine-Kinase Inhibitors

7.9Drug-Food Interactions Consumption

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Strengths and forms

Official product information