Levothyroxine Drug Information
Generic name: LEVOTHYROXINE SODIUM
Uses of Levothyroxine
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 may induce hyperthyroidism.
Levothyroxine sodium tablets are not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis. 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
Dosage & Administration of Levothyroxine
Important Administration Instructions
Administer levothyroxine sodium tablets as a single daily dose, on an empty stomach, one-half to one hour before breakfast with a full glass of water to avoid choking or gagging. Administer levothyroxine sodium tablets at least 4 hours before or after drugs known to interfere with levothyroxine sodium absorption. Evaluate the need for dosage adjustments when regularly administering within one hour of certain foods that may affect levothyroxine sodium tablets absorption.
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.
Important Considerations for Dosing
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. 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. For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal.
For secondary or tertiary hypothyroidism, serum TSH is not a reliable measure of levothyroxine sodium 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. 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. The peak therapeutic effect of a given dose of levothyroxine sodium tablets may not be attained for 4 to 6 weeks.
Recommended Dosage and Titration 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.
Table 1. Levothyroxine Sodium Tablets Dosing Guidelines for Hypothyroidism in Adults* *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.
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. Table 2. Levothyroxine Sodium Tablets Dosing Guidelines for Hypothyroidism in Pediatric Patients *Adjust dosage based on clinical response and laboratory parameters.
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. Table 3.
Levothyroxine Sodium Tablet Dosing Guidelines for Hypothyroidism in Pregnant Patients TSH Suppression in Well-differentiated Thyroid Cancer in Adult and Pediatric Patients The levothyroxine sodium dosage is based on the target level of TSH suppression for the stage and clinical status of thyroid cancer.
Monitoring
TSH and/or Thyroxine (T4) Levels 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.
Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of levothyroxine sodium 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 therapy and/or of the serum TSH to decrease below 20 mIU per litre 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. Secondary and Tertiary Hypothyroidism Monitor serum free-T4 levels and maintain in the upper half of the normal range in these patients.
| *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) ]. | ||
| Patient Population | Starting Dosage | Dosage Titration Based on serum TSH or Free-T4 |
| Adults diagnosed with hypothyroidism | Full replacement dose is 1.6 mcg/kg/day. Some patients require a lower starting dose. | Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed until the patient is euthyroid. |
| Adults at risk for atrial fibrillation or with underlying cardiac disease | Lower starting dose (less than 1.6 mcg/kg/day) | Titrate dosage every 6 to 8 weeks, as needed until the patient is euthyroid. |
| Geriatric patients | Lower starting dose (less than 1.6 mcg/kg/day) | |
| Age | Starting Daily Dosage Per Kg Body Weight* |
|---|---|
| 0 to 3 months | 10 to 15 mcg/kg/day |
| 3 to 6 months | 8 to 10 mcg/kg/day |
| 6 to 12 months | 6 to 8 mcg/kg/day |
| 1 to 5 years | 5 to 6 mcg/kg/day |
| 6 to 12 years | 4 to 5 mcg/kg/day |
| Greater than 12 years but growth and puberty incomplete | 2 to 3 mcg/kg/day |
| Growth and puberty complete | 1.6 mcg/kg/day |
| *Adjust dosage based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4) ]. | |
| Patient Population | Starting Dosage | Dose Adjustment and Titration |
|---|---|---|
| Pre-existing primary hypothyroidism with serum TSH above normal trimester- specific range | Pre-pregnancy dosage may increase during pregnancy | Increase levothyroxine sodium 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 dosage to pre-pregnancy levels immediately after delivery. Monitor serum TSH 4 to 8 weeks postpartum. |
| New onset hypothyroidism (TSH ≥10 mIU per liter) | 1.6 mcg/kg/day | Monitor serum TSH every 4 weeks and adjust levothyroxine sodium dosage until serum TSH is within normal trimester-specific range. |
| New onset hypothyroidism (TSH < 10 mIU per liter) | 1.0 mcg/kg/day |
| *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) ]. | ||
| Patient Population | Starting Dosage | Dosage Titration Based on serum TSH or Free-T4 |
| Adults diagnosed with hypothyroidism | Full replacement dose is 1.6 mcg/kg/day. Some patients require a lower starting dose. | Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed until the patient is euthyroid. |
| Adults at risk for atrial fibrillation or with underlying cardiac disease | Lower starting dose (less than 1.6 mcg/kg/day) | Titrate dosage every 6 to 8 weeks, as needed until the patient is euthyroid. |
| Geriatric patients | Lower starting dose (less than 1.6 mcg/kg/day) | |
| Age | Starting Daily Dosage Per Kg Body Weight* |
|---|---|
| 0 to 3 months | 10 to 15 mcg/kg/day |
| 3 to 6 months | 8 to 10 mcg/kg/day |
| 6 to 12 months | 6 to 8 mcg/kg/day |
| 1 to 5 years | 5 to 6 mcg/kg/day |
| 6 to 12 years | 4 to 5 mcg/kg/day |
| Greater than 12 years but growth and puberty incomplete | 2 to 3 mcg/kg/day |
| Growth and puberty complete | 1.6 mcg/kg/day |
| *Adjust dosage based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4) ]. | |
| Patient Population | Starting Dosage | Dose Adjustment and Titration |
|---|---|---|
| Pre-existing primary hypothyroidism with serum TSH above normal trimester- specific range | Pre-pregnancy dosage may increase during pregnancy | Increase levothyroxine sodium 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 dosage to pre-pregnancy levels immediately after delivery. Monitor serum TSH 4 to 8 weeks postpartum. |
| New onset hypothyroidism (TSH ≥10 mIU per liter) | 1.6 mcg/kg/day | Monitor serum TSH every 4 weeks and adjust levothyroxine sodium dosage until serum TSH is within normal trimester-specific range. |
| New onset hypothyroidism (TSH < 10 mIU per liter) | 1.0 mcg/kg/day |
| *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) ]. | ||
| Patient Population | Starting Dosage | Dosage Titration Based on serum TSH or Free-T4 |
| Adults diagnosed with hypothyroidism | Full replacement dose is 1.6 mcg/kg/day. Some patients require a lower starting dose. | Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed until the patient is euthyroid. |
| Adults at risk for atrial fibrillation or with underlying cardiac disease | Lower starting dose (less than 1.6 mcg/kg/day) | Titrate dosage every 6 to 8 weeks, as needed until the patient is euthyroid. |
| Geriatric patients | Lower starting dose (less than 1.6 mcg/kg/day) | |
| Age | Starting Daily Dosage Per Kg Body Weight* |
|---|---|
| 0 to 3 months | 10 to 15 mcg/kg/day |
| 3 to 6 months | 8 to 10 mcg/kg/day |
| 6 to 12 months | 6 to 8 mcg/kg/day |
| 1 to 5 years | 5 to 6 mcg/kg/day |
| 6 to 12 years | 4 to 5 mcg/kg/day |
| Greater than 12 years but growth and puberty incomplete | 2 to 3 mcg/kg/day |
| Growth and puberty complete | 1.6 mcg/kg/day |
| *Adjust dosage based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4) ]. | |
| Patient Population | Starting Dosage | Dose Adjustment and Titration |
|---|---|---|
| Pre-existing primary hypothyroidism with serum TSH above normal trimester- specific range | Pre-pregnancy dosage may increase during pregnancy | Increase levothyroxine sodium 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 dosage to pre-pregnancy levels immediately after delivery. Monitor serum TSH 4 to 8 weeks postpartum. |
| New onset hypothyroidism (TSH ≥10 mIU per liter) | 1.6 mcg/kg/day | Monitor serum TSH every 4 weeks and adjust levothyroxine sodium dosage until serum TSH is within normal trimester-specific range. |
| New onset hypothyroidism (TSH < 10 mIU per liter) | 1.0 mcg/kg/day |
Side Effects of Levothyroxine
Adverse reactions associated with levothyroxine sodium therapy are primarily those of hyperthyroidism due to therapeutic overdosage. 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. To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Warnings & Cautions for Levothyroxine
Serious Risks Related to Overtreatment or Undertreatment with Levothyroxine Sodium Tablets Levothyroxine sodium tablets 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.
Titrate the dose of levothyroxine sodium tablets carefully and monitor response to titration to avoid these effects. Consider the potential for food or drug interactions and adjust the administration or dosage of levothyroxine sodium tablets as needed.
Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease 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 therapy in this population at lower doses than those recommended in younger individuals or in patients without cardiac disease. Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive levothyroxine sodium therapy.
Monitor patients receiving concomitant levothyroxine sodium 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
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.
Acute Adrenal Crisis in Patients with Concomitant Adrenal Insufficiency 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.
Worsening of Diabetic Control 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.
Decreased Bone Mineral Density Associated with Thyroid Hormone Over-Replacement 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 that achieves the desired clinical and biochemical response to mitigate this risk.
Risk of Allergic Reactions Due to Tartrazine
This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Drug Interactions with Levothyroxine
Drugs 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) Table 6.
Drugs That May Alter T4 and Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism) 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.
Table 8. Drugs That May Decrease Conversion of T4 to T3
Antidiabetic 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.
Oral 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.
Digitalis 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.
Antidepressant 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.
Ketamine
Concurrent use of ketamine and levothyroxine sodium may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients.
Sympathomimetics
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.
Tyrosine-Kinase Inhibitors
Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. Closely monitor TSH levels in such patients.
Drug-Food Interactions Consumption of certain foods may affect levothyroxine sodium absorption thereby necessitating adjustments in dosing. Soybean flour, cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine sodium from the gastrointestinal tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability.
Drug-Laboratory Test Interactions 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.
| 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. |
| 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. |
| 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 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. |
| 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
Pregnancy Safety for Levothyroxine
Pregnancy 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 dosage adjusted during pregnancy (see Clinical Considerations).
Animal reproductive studies have not been conducted with levothyroxine sodium. Levothyroxine sodium 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 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 requirements. Serum TSH levels should be monitored and the levothyroxine sodium dosage adjusted during pregnancy.
Since postpartum TSH levels are similar to preconception values, the levothyroxine sodium dosage should return to the pre-pregnancy dose immediately after delivery.
Pediatric Use of Levothyroxine
Pediatric Use Levothyroxine sodium is indicated in patients from birth to less than 17 years of age: As a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. 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 therapy immediately upon diagnosis. Levothyroxine is generally continued for life in these patients. Closely monitor infants during the first 2 weeks of levothyroxine sodium therapy for cardiac overload and arrhythmias.
Contraindications for Levothyroxine
Levothyroxine sodium tablets are contraindicated in patients with uncorrected adrenal insufficiency. Uncorrected adrenal insufficiency.
Overdosage Information for Levothyroxine
The signs and symptoms of overdosage are those of hyperthyroidism. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported.
Seizures occurred in a 3-year-old child ingesting 3.6 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium. Reduce the levothyroxine sodium 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.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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