Hypothyroidism ERMEZA is 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 ERMEZA is 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:
ERMEZA is 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 ERMEZA may induce hyperthyroidism [see Warnings and Precautions (5.1) ].
ERMEZA is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis. ERMEZA is levothyroxine sodium (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: 3. Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients 4. Not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis
Contraindications
ERMEZA is contraindicated in patients with:
Uncorrected adrenal insufficiency [see Warnings and Precautions (5.4) ] .
Hypersensitivity to glycerin and edetate disodium, inactive ingredients in ERMEZA [see Adverse Reactions (6) and Pediatric Use (8.4) ] .
Uncorrected adrenal insufficiency. ( 4 )
Hypersensitivity to glycerin and edetate disodium. ( 4 )
Warnings and precautions
Serious risks related to overtreatment or undertreatment of ERMEZA: Titrate the dose of ERMEZA carefully and monitor response to titration. ( 5.1 )
Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate ERMEZA 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 ERMEZA 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. Carefully monitor glycemic control after starting, changing, or discontinuing thyroid hormone therapy. ( 5.5 )
Decreased bone mineral density associated with thyroid hormone over-replacement: Over-replacement can increase bone resorption and decrease bone mineral density. Give the lowest effective dose. ( 5.6 )
5.1Serious Risks Related to Overtreatment or Undertreatment of
ERMEZA ERMEZA has a narrow therapeutic index. Overtreatment or undertreatment with ERMEZA 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 ERMEZA 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 ERMEZA as needed [see Dosage and Administration (2.1) , Drug Interactions (7.1) , and Clinical Pharmacology (12.3) ] .
5.2 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 ERMEZA 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 ERMEZA therapy. Monitor patients receiving concomitant ERMEZA and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiac symptoms develop or worsen, reduce the ERMEZA dose or withhold for one week and restart at a lower dose.
5.3Myxedema 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.
5.4Acute 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 ERMEZA [see Contraindications (4) ].
5.5Worsening 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 ERMEZA [see Drug Interactions (7.2) ] .
5.6Decreased 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 ERMEZA that achieves the desired clinical and biochemical response to mitigate this risk.
Interactions
See full prescribing information for drugs that affect thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, metabolism, protein binding, and target tissue response) and may alter the therapeutic response to ERMEZA. ( 7 )
7.1Drugs Known to Affect Thyroid Hormone Pharmacokinetics
Many drugs can exert effects on thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, metabolism, protein binding, and target tissue response) and may alter the therapeutic response to ERMEZA (Tables 5 to 8). Table 5. Drugs That May Decrease T4 Absorption (Hypothyroidism) Potential impact: Concurrent use may reduce the efficacy of ERMEZA 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 ERMEZA at least 4 hours apart from these agents. Orlistat Monitor patients treated concomitantly with orlistat and ERMEZA for changes in thyroid function. Bile Acid Sequestrants -Colesevelam -Cholestyramine -Colestipol Ion Exchange Resins -Kayexalate Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption.
Administer ERMEZA at least 4 hours prior to these drugs or monitor TSH levels. Other drugs: Proton Pump Inhibitors Sucralfate Antacids - 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 ERMEZA 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 ERMEZA 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.
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 the 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 decrease or normal free-T3) in clinically euthyroid patients.
7.2Antidiabetic Therapy Addition of
ERMEZA 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
ERMEZA 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 ERMEZA dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.
7.4Digitalis Glycosides
ERMEZA 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 ERMEZA 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. ERMEZA may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on ERMEZA may result in increased ERMEZA requirements.
7.6Ketamine
Concurrent use of ketamine and ERMEZA may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients.
7.7Sympathomimetics
Concurrent use of sympathomimetics and ERMEZA 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 ERMEZA absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1) ] . Soybean products, such as infant formula and soybean flour, cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of ERMEZA from the gastrointestinal tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability.
7.10Drug-Laboratory Test Interactions
Consider changes in TBG concentration when interpreting T4 and T3 values. Measure and evaluate
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
The clinical experience, including data from post-marketing studies in pregnant women treated with oral levothyroxine, to maintain a 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 hypothyroidism in pregnancy. Since TSH levels may increase during pregnancy, TSH should be monitored, and ERMEZA dosage adjusted during pregnancy (see Clinical Considerations ) .
Animal reproduction studies have not been conducted with levothyroxine sodium. ERMEZA 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 ERMEZA requirements.
Serum TSH levels should be monitored, and the ERMEZA dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the ERMEZA dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3) ].
Adverse reactions
Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5) , Overdosage (10) ] . They include the following:
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 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 Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Composition
Active ingredients
LEVOTHYROXINE SODIUM 150MCG/5ML
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application NDA215809.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
