Levothyroxine sodium, the sodium salt of the l-isomer of thyroxine, is a thyroid agent.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Levothyroxine sodium tablets and oral solution are used as replacement in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism in adult and pediatric patients (including neonates).2, 4, 5, 6, 140, 141, 142 Levothyroxine sodium capsules are indicated for this use in adult and pediatric patients 6 years of age and older.3
Levothyroxine is not recommended for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients nor for the treatment of hypothyroidism during recovery of subacute thyroiditis.2, 3, 4, 5, 6, 140, 141, 142
In the United States (and other areas of iodine sufficiency), primary hypothyroidism resulting from autoimmune disease (Hashimoto's thyroiditis) is the most common form of the condition.200, 201 The most recent guidelines from the American Association of Clinical Endocrinologists (AACE)/American Thyroid Association (ATA) and from the ATA Task Force on thyroid hormone replacement recommend levothyroxine as the treatment of choice for primary hypothyroidism.201, 202
Hypothyroidism due to pituitary (secondary) or hypothalamic (tertiary) disorders is relatively rare.200 For treatment of secondary or tertiary hypothyroidism, guidelines also recommend treatment with levothyroxine, after diagnosis and with appropriate monitoring.203
For neonates diagnosed with congenital hypothyroidism, guidelines from the American Academy of Pediatrics (AAP) recommend initiating treatment as soon as possible (by 2 weeks of age if identified by newborn screening) with levothyroxine tablets, preferably administered by the enteral route (i.e., tablets crushed and mixed in human milk, formula, or water).204 Alternative dosage forms include a commercially available oral solution and an IV† administered solution.204 Dosing requirements may differ between dosage forms.204
Pituitary Thyrotropin Suppression
Levothyroxine sodium tablets and oral solution are used to suppress the secretion of thyrotropin (thyroid-stimulating hormone, TSH) as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent, well-differentiated thyroid cancer in adult and pediatric patients (including neonates).2, 4, 5, 6, 140, 141, 142 Levothyroxine sodium capsules are indicated for this use in adult and pediatric patients 6 years of age and older.3
In the United States, the estimated annual number of new cases of thyroid cancer is around 44,000.205 Most are well-differentiated cancers, with papillary thyroid cancers accounting for about 84%.205 Surgery is recommended for well-differentiated thyroid cancers, with additional therapies based on risk of recurrence.205, 206 Adjuvant therapy for cancers with a low risk of recurrence (<5%) include levothyroxine for thyrotropin suppression, with an initial target thyroglobulin level of 0.1-0.5 mIU/L.205 For intermediate- (10-20% risk of recurrence) and high-risk cancers (30-35% risk), therapy with radioactive iodine along with thyrotropin suppression are recommended.205, 206
Levothyroxine sodium injection is used IV for the treatment of myxedema coma in adult patients.165, 166 The IV dosage form is not recommended for use as a substitute for oral levothyroxine as there is no accurate dose conversion.166
Myxedema coma, also referred to as decompensated hypothyroidism, is a rare endocrine emergency, which presents with a variety of symptoms, including mental status changes, bradycardia, hypotension, and/or hypothermia.207 Supportive measures should be aimed at cardiovascular, respiratory, and neurologic functions, along with management of underlying conditions.207, 208 Administration of hydrocortisone is recommended early in the course of treatment, before administration of thyroid hormone.207 Levothyroxine is recommended as the thyroid replacement of choice to resolve symptoms of hypothyroidism and normalize circulating levels of serum thyrotropin and thyroid hormones.202 The most recent guidelines from the ATA recommend a TSH therapeutic target range of 0.4-4.0 mIU/L.202
Dispensing and Administration Precautions
Levothyroxine sodium is administered orally or by IV injection.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 It is available for oral administration as a tablet, capsule, or oral solution;2, 3, 4, 5, 6, 140, 141, 142 approved oral preparations may not be therapeutically equivalent to one another (consult the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations [Orange Book] for current information).164 Levothyroxine sodium is available for IV administration as a solution for injection or a powder for reconstitution and injection.165, 166
Levothyroxine sodium tablets and capsules are usually administered orally on an empty stomach, preferably one-half to one hour before breakfast.3, 6, 140, 141, 142 The manufacturers state that Levoxyl® and Unithroid® tablets should be taken with a full glass of water to prevent choking or gagging.140, 141
In individuals who are unable to swallow the intact tablets (e.g., pediatric patients), the appropriate dose of levothyroxine tablets may be crushed and placed in a small amount (5-10 mL) of water; the resultant suspension should be administered by spoon or dropper immediately and should not be stored.6, 140, 141, 142 Do not administer the crushed tablet in foods that decrease levothyroxine absorption (e.g., soybean-based infant formula).6, 140, 141, 142
Levothyroxine capsules should be swallowed whole; do not cut, crush, or chew.3 In pediatric patients, the capsules are only indicated for use in those 6 years of age or older who can swallow an intact capsule.3
Administer Ermeza® (levothyroxine sodium oral solution) orally on an empty stomach, one-half to one hour before breakfast.4 Administer the solution directly into the mouth using the 5 mL or 10 mL oral syringe provided in the original carton; a household teaspoon or tablespoon is not an adequate measuring device.4 Ermeza® is available as a 30 mcg/mL solution: consult the prescribing information for detailed information on how to convert the prescribed dosage of levothyroxine in mcg to mL of Ermeza® oral solution.4 Once the dose has been converted to mL, it should be rounded up or down to the nearest syringe graduation (0.1 mL for doses up to 5 mL or 0.2 mL for doses up to 10 mL).4
Administer Thyquidity® (levothyroxine sodium oral solution) orally on an empty stomach, one-half to one hour before breakfast.5 Administer the solution directly into the mouth using a calibrated oral syringe provided by the pharmacy; a household teaspoon or tablespoon is not an adequate measuring device.5
Administer Tirosint-SOL® (levothyroxine sodium oral solution) orally on an empty stomach, 15 minutes before breakfast.2 The oral solution may be administered by squeezing the contents of a single-dose ampule directly into the mouth or onto a spoon and consuming immediately; the solution also may be diluted in water prior to administration.2 If diluting in water, squeeze the contents of a single ampule into a cup of water; stir the diluted solution and drink all of it immediately.2 Rinse the cup with additional water and drink the contents to ensure that the total dose is taken.2 Do not dilute the oral solution in a medium other than water.2
Oral levothyroxine sodium should be administered at least 4 hours apart from drugs that are known to interfere with its absorption.2, 3, 4, 5, 6, 140, 141, 142 Evaluate the need for dosage adjustments when oral levothyroxine sodium is regularly administered within 1 hour of foods that affect absorption.2, 3, 4, 5, 6, 140, 141, 142
Store capsules and tablets at room temperature (20-25°C; excursions permitted between 15-30°C);3, 6, 140, 141, 142 store away from heat, moisture, and light.3, 6, 141, 142 For Euthyrox® and levothyroxine sodium capsules, do not separate the individual cavities containing the tablet or capsule from the intact blister and do not remove individual tablets or capsules from the blister packaging until ready to use.3, 6
Store Ermeza® at 20-25°C (excursions permitted between 15-30°C) and protect from light; store and dispense in the original bottle, and use within 90 days of opening.4
Store Thyquidity® at 20-25°C and protect from light; store and dispense in the original bottle, and use within 8 weeks of opening.5
Store Tirosint-SOL® in the original container (closed pouch) at 20-25°C (excursions permitted between 15-30°C); keep ampules in the pouch until ready to use.2 Use the oral solution within 3 months of opening the pouch.2
Levothyroxine sodium powder for injection should be reconstituted by adding 5 mL of 0.9% sodium chloride injection to a vial labeled as containing 100, 200, or 500 mcg of the drug, and shaking the vial to mix completely.165 The resultant solutions contain approximately 20, 40, or 100 mcg/mL, respectively, of levothyroxine sodium.165 The solution should not be admixed with other IV infusion solutions.165
Store levothyroxine sodium powder for injection at 20-25°C protected from light.165 Reconstituted levothyroxine sodium solution is stable for 4 hours; discard any unused solution.165
Administer levothyroxine sodium injection solution as an IV injection at a rate not to exceed 100 mcg/minute.166 The solution should not be admixed with other IV infusion solutions.166
Store levothyroxine sodium injection solution at 20-25°C in the original carton to protect from light.166 Unopened vials may be stored for up to 24 hours exposed to indoor lighting outside the carton.166 The injection solution does not contain a preservative; discard any unused solution.166
The dosage of levothyroxine sodium for hypothyroidism or pituitary TSH suppression depends on a variety of factors, including patient age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food, and the specific nature of the condition being treated.2, 3, 4, 5, 6, 140, 141, 142 Dosage must be individualized to account for these factors, with dosage adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters.2, 3, 4, 5, 6, 140, 141, 142
For the management of primary, secondary, or tertiary hypothyroidism in nonelderly, nonpregnant adults without risk factors for atrial fibrillation or underlying cardiac disease, the recommended starting dosage of oral levothyroxine is the full replacement dosage of 1.6 mcg/kg per day; however, some patients may require a lower starting dosage.2, 3, 4, 5, 6, 140, 141, 142 Titrate the dosage by 12.5-25 mcg increments every 4-6 weeks as needed based on serum TSH or free T4 until the patient is euthyroid.2, 3, 4, 5, 6, 140, 141, 142 Dosages >200 mcg/day are seldom required; an inadequate response to daily dosages >300 mcg/day is rare and may indicate poor compliance, malabsorption, drug interactions, or a combination of these factors.2, 3, 4, 5, 6, 140, 141, 142
Adults at risk for atrial fibrillation, adults with underlying cardiac disease, and geriatric patients should receive lower starting dosages (e.g., 12.5-25 mcg/day); in these patients, the dosage of levothyroxine should be titrated every 6-8 weeks as needed based on serum TSH or free T4 until the patient is euthyroid.2, 3, 4, 5, 6, 140, 141, 142
In adults with severe, long-standing hypothyroidism, initiate levothyroxine therapy at a dosage of 12.5-25 mcg/day; adjust the dosage in increments of 12.5-25 mcg every 2-4 weeks until the patient is clinically euthyroid and serum TSH is normalized.3, 5, 6, 140, 141
In pregnant patients with pre-existing hypothyroidism, an increase in oral levothyroxine dosage may be necessary during pregnancy; serum TSH and free T4 should be measured as soon as pregnancy is confirmed and, at a minimum, during each trimester of pregnancy.2, 3, 4, 5, 6, 140, 141, 142 Dosage of levothyroxine should be titrated to maintain serum TSH in the trimester-specific reference range.2, 3, 4, 5, 6, 140, 141, 142 When needed, the dosage of oral levothyroxine may be increased in increments of 12.5-25 mcg/day; TSH should be monitored every 4 weeks until a stable dosage is reached and serum TSH is within the normal trimester-specific range.2, 3, 4, 5, 6, 140, 141, 142 Reduce the dosage of levothyroxine to pre-pregnancy levels immediately after delivery and monitor serum TSH 4-8 weeks postpartum.2, 3, 4, 5, 6, 140, 141, 142
In pregnant patients with new-onset hypothyroidism, the recommended dosage of oral levothyroxine depends on the patient's TSH level.2, 3, 4, 5, 6, 140, 141, 142 If the TSH level is ≥10 mIU/L, the recommended starting dosage is 1.6 mcg/kg per day; if the TSH level is <10 mIU/L, the recommended starting dosage is 1 mcg/kg per day.2, 3, 4, 6, 140, 141, 142 Serum TSH should be monitored every 4 weeks, and the dosage of levothyroxine adjusted until serum TSH is within the normal trimester-specific range.2, 3, 4, 5, 6, 140, 141, 142
For the treatment of myxedema coma, levothyroxine sodium is given by IV injection;165, 166 oral administration is not recommended because absorption of the drug from the GI tract is unpredictable in such patients.2, 3, 4, 5, 6, 140, 141, 142
Initial and maintenance dosages of IV levothyroxine sodium should be selected after taking into account the age, general physical condition, and cardiac risk factors of the patient, as well as the clinical severity and duration of myxedema symptoms.165, 166 The manufacturer states that the initial adult IV loading dose for the treatment of myxedema coma is 300-500 mcg.165, 166 Some experts recommend a slightly lower IV loading dose of 200-400 mcg.202 Lower IV maintenance dosages of 50-100 mcg once daily should be administered thereafter as clinically indicated until the patient's condition is stabilized and the drug can be given orally.165, 166
In the geriatric population and in patients with underlying cardiovascular disease, administration of IV levothyroxine sodium, especially loading doses exceeding 500 mcg, may precipitate severe adverse cardiovascular effects (e.g., arrhythmias, tachycardia, myocardial ischemia or infarction, worsening of heart failure, death).165 The manufacturer states that cautious use (e.g., dosages in the lower end of the recommended range) of IV levothyroxine sodium may be warranted in geriatric patients and in those with known cardiac risk factors.165, 166
Pituitary Thyrotropin Suppression
The dosage of levothyroxine sodium for TSH suppression in adult patients with well-differentiated thyroid cancer is based on the target level of TSH suppression for the stage and clinical status of the cancer.2, 4, 6, 140, 141, 142 In general, TSH is suppressed to <0.1 mIU/L, which usually requires a dosage >2 mcg/kg per day; however, in patients with high-risk tumors, the target TSH suppression level may be lower.3, 5
For the treatment of primary, secondary, or tertiary hypothyroidism in pediatric patients, the recommended initial dosage of levothyroxine sodium therapy is based on body weight and age (see Table 1).2, 3, 4, 5, 6, 140, 141, 142 Dosage may be titrated every 2 weeks as needed based on serum TSH or free T4 until the patient is euthyroid.2, 4, 142 The general aim of therapy is to normalize TSH; however, TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback.2, 3, 4, 5, 6, 140, 141, 142 If serum T4 does not increase into the upper half of the normal range within 2 weeks of treatment initiation and/or serum TSH decreases to <20 mIU/L within 4 weeks of treatment initiation, therapy may be inadequate.2, 3, 4, 5, 6, 140, 141, 142 Assess compliance, dosage of medication administered, and method of administration prior to increasing the dosage.2, 3, 4, 5, 6, 140, 141, 142
Age | Daily Dose (mcg/kg) |
|---|---|
0-3 months | 10-15 |
3-6 months | 8-10 |
6-12 months | 6-8 |
1-5 years | 5-6 |
6-12 years | 4-5 |
>12 years but growth and puberty incomplete | 2-3 |
Growth and puberty complete | 1.6 |
A lower initial dosage should be considered in neonates (birth to 3 months of age) at risk of cardiac failure; dosage may be increased at intervals of 4-6 weeks as needed based on clinical and laboratory response to treatment.2, 4, 5, 6, 140, 141, 142
The manufacturers state that the risk of hyperactivity may be minimized by initiating therapy at a dosage approximately one-fourth of the recommended full replacement dosa the dosage may then be increased by an amount equal to one-fourth the full recommended replacement dosage at weekly intervals until the full recommended replacement dosage is reached.2, 3, 4, 5, 6, 140, 141, 142
Pituitary Thyrotropin Suppression
The dosage of levothyroxine sodium for TSH suppression in pediatric patients with well-differentiated thyroid cancer is based on the target level of TSH suppression for the stage and clinical status of the cancer.2, 4, 6, 140, 141, 142 In general, TSH is suppressed to <0.1 mIU/L, which usually requires a dosage >2 mcg/kg per day; however, in patients with high-risk tumors, the target TSH suppression level may be lower.3, 5, 6
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.2, 3, 4, 5, 6, 140, 141, 142
The manufacturer makes no specific dosage recommendations for patients with renal impairment.2, 3, 4, 5, 6, 140, 141, 142
Geriatric patients should receive lower starting dosages of oral levothyroxine (e.g., 12.5-25 mcg/day); in these patients, the dosage of levothyroxine should be titrated every 6-8 weeks as needed based on serum TSH or free T4 until the patient is euthyroid.2, 3, 4, 5, 6, 140, 141, 142
Cautious use (e.g., dosages in the lower end of the recommended range) of IV levothyroxine sodium may be warranted in geriatric patients.165, 166
Use for the Treatment of Obesity or for Weight Loss
A boxed warning that levothyroxine should not be used for the treatment of obesity or for weight loss is included in the prescribing information.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Thyroid hormones, including levothyroxine, should not be used for the treatment of obesity or for weight loss, either alone or in combination with other agents.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 In euthyroid patients, dosages within the range of daily hormonal requirements are ineffective for weight reduction, and larger dosages may produce serious or life-threatening toxicity (particularly when given together with sympathomimetic amines such as those used for anorectic effects).2, 3, 4, 5, 6, 140, 141, 142
Risk of Overtreatment or Undertreatment with Levothyroxine
Levothyroxine has a narrow therapeutic index.2, 3, 4, 5, 6, 140, 141, 142 Overtreatment or undertreatment with levothyroxine may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, GI function, and glucose and lipid metabolism.2, 3, 4, 5, 6, 140, 141, 142 In pediatric patients with congenital or acquired hypothyroidism, undertreatment may adversely affect cognitive development and linear growth; overtreatment may lead to craniosynostosis and acceleration of bone age.2, 3, 4, 5, 6, 140, 141, 142
Titrate the dosage of oral levothyroxine carefully, and monitor response to titration.2, 3, 4, 5, 6, 140, 141, 142 Consider the potential for food or drug interactions and adjust the administration or dosage of levothyroxine as needed.2, 3, 4, 5, 6, 140, 141, 142
Cardiac Adverse Reactions in Geriatric Patients and Patients with Underlying Cardiovascular Disease
Overtreatment with oral levothyroxine can increase heart rate, cardiac wall thickness, and cardiac contractility; it may also precipitate angina or arrhythmias, particularly in patients with cardiovascular disease or geriatric patients.2, 3, 4, 5, 6, 140, 141, 142
For elderly patients and patients with cardiovascular disease, initiate oral levothyroxine at lower dosages than those recommended in younger individuals or in patients without cardiovascular disease.2, 3, 4, 5, 6, 140, 141, 142
Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive oral levothyroxine therapy.2, 3, 4, 5, 6, 140, 141, 142 Monitor for signs and symptoms of coronary insufficiency in patients receiving oral levothyroxine concomitantly with sympathomimetic agents.2, 3, 4, 5, 6, 140, 141, 142 If cardiac symptoms develop or worsen, reduce the dosage of oral levothyroxine or withhold treatment for 1 week and restart at a lower dosage.2, 3, 4, 5, 6, 140, 141, 142
Excessive bolus dosing of IV levothyroxine (greater than 500 mcg) has been associated with cardiac complications, including arrhythmia, tachycardia, myocardial ischemia, myocardial infarction, worsening congestive heart failure, and death.165 The risk of such complications increases in patients with underlying cardiovascular disease and elderly patients.165, 166 Use caution when administering IV levothyroxine to elderly patients or patients with underlying cardiovascular disease; consider using dosages in the lower end of the recommended range.165, 166 Close observation following administration of IV levothyroxine is advised.165
Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism.2, 3, 4, 5, 6, 140, 141, 142 Absorption of levothyroxine from the GI tract may be unpredictable in patients with myxedema coma; therefore, the use of oral thyroid hormone products is not recommended to treat myxedema coma.2, 3, 4, 5, 6, 140, 141, 142 Myxedema coma should be treated with IV thyroid hormone products.2, 3, 4, 5, 6, 140, 141, 142
Acute Adrenal Crisis in Patients with Concomitant Adrenal Insufficiency
Thyroid hormone increases metabolic clearance of glucocorticoids.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 In patients with adrenal insufficiency, initiating thyroid hormone therapy prior to initiating glucocorticoid therapy may precipitate an acute adrenal crisis.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with levothyroxine.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Administer replacement glucocorticoids prior to initiating IV levothyroxine until adrenal function has been adequately assessed, as chronic autoimmune thyroiditis (which can lead to myxedema coma) may occur in association with adrenal insufficiency or other autoimmune disorders (e.g., pernicious anemia, diabetes insipidus).165, 166 When initiating IV levothyroxine in patients with myxedema coma, monitor for previously undiagnosed diabetes insipidus.165
Levothyroxine therapy may worsen glycemic control in patients with diabetes mellitus and lead to increased antidiabetic agent or insulin requirements.2, 3, 4, 5, 6, 140, 141, 142 Carefully monitor glycemic control when starting, changing, or discontinuing levothyroxine therapy.2, 3, 4, 5, 6, 140, 141, 142
Decreased Bone Mineral Density Associated with Thyroid Hormone Overreplacement
Thyroid hormone overreplacement may lead to increased bone resorption and decreased bone mineral density, particularly in postmenopausal women.2, 3, 4, 5, 6, 140, 141, 142 Increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorus, elevations in bone alkaline phosphatase, and suppressed serum parathyroid hormone levels.2, 3, 4, 5, 6, 140, 141, 142
Administer the minimum dosage of levothyroxine necessary to achieve the desired clinical and biochemical response.2, 3, 4, 5, 6, 140, 141, 142
Clinical experience, including data from published postmarketing studies, has not identified increased rates of major birth defects, miscarriages, or other adverse maternal or fetal outcomes in pregnant women treated with oral levothyroxine to maintain a euthyroid state.2, 3, 4, 5, 6, 140, 141, 142 Maternal hypothyroidism during pregnancy may increase the risk of complications, including spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, and premature delivery.2, 3, 4, 5, 6, 140, 141, 142 Untreated maternal hypothyroidism may also adversely affect fetal neurocognitive development.2, 3, 4, 5, 6, 140, 141, 142 Levothyroxine should not be discontinued during pregnancy, and hypothyroidism diagnosed during pregnancy should be promptly treated.2, 3, 4, 5, 6, 140, 141, 142
Because thyroid-stimulating hormone (TSH) levels may increase during pregnancy, levothyroxine requirements may also be increased; TSH should be monitored, and the dosage of levothyroxine should be adjusted as necessary.2, 3, 4, 5, 6, 140, 141, 142 Postpartum TSH levels are similar to preconception values, so the levothyroxine dosage should be decreased to the pre-pregnancy dosage immediately after delivery.2, 3, 4, 5, 6, 140, 141, 142
There are no reported cases of IV levothyroxine being used to treat myxedema coma in pregnant patients; however, because nontreatment is associated with a high probability of significant morbidity or mortality to the maternal patient and the fetus, pregnant patients who develop myxedema should be treated with IV levothyroxine.165, 166
Published studies report that levothyroxine is present in human milk following oral administration.2, 3, 4, 5, 6, 140, 141, 142 No adverse effects on the breast-fed infant have been reported.2, 4, 5, 142 The effects of levothyroxine on milk production are not known; however, adequate levothyroxine treatment during lactation may normalize milk production in hypothyroid lactating mothers with low milk supply.2, 3, 4, 5, 6, 140, 141, 142
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed infant from levothyroxine or from the underlying maternal condition.2, 3, 4, 5, 6, 140, 141, 142
There are no reported cases of IV levothyroxine being used to treat myxedema coma in lactating patients;165, 166 however, because nontreatment is associated with a high probability of significant morbidity or mortality, breastfeeding patients who develop myxedema should be treated with IV levothyroxine.165
Safety and effectiveness of levothyroxine tablets and oral solution have been established for use as replacement therapy for primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism in pediatric patients from birth to <17 years of age.2, 4, 5, 6, 140, 141, 142 Safety and effectiveness have also been established for use as an adjunct to surgery and radioiodine therapy for management of thyrotropin-dependent well-differentiated thyroid cancer in pediatric patients from birth to <17 years of age.2, 4, 142
Safety and effectiveness of levothyroxine oral capsules have been established in pediatric patients ≥6 years of age.3
Rapid restoration of normal serum T4 concentrations in patients with congenital hypothyroidism is essential for preventing adverse effects on cognitive development or overall growth and maturation.2, 3, 4, 5, 6, 140, 141, 142 Levothyroxine therapy should be initiated immediately upon diagnosis; it is typically continued for life in patients with congenital hypothyroidism.2, 3, 4, 5, 6, 140, 141, 142
In pediatric patients without an established diagnosis of permanent hypothyroidism, discontinue levothyroxine for a trial period (after the patient is at least 3 years of age) and obtain serum T4 and TSH levels at the end of the trial period; use laboratory test results and clinical assessments to guide diagnosis and treatment, if warranted.3, 6, 140, 141
Closely monitor infants and children for cardiac overload, arrhythmia, and aspiration from avid suckling during the first 2 weeks of levothyroxine therapy.2, 3, 4, 5, 6, 140, 141, 142
Levothyroxine oral solutions contain glycerin or glycerol.2, 4, 5 These inactive ingredients may cause GI irritation resulting in vomiting and/or osmotic diarrhea; patients in the first 3 months of life may be particularly susceptible to serious fluid and electrolyte complications from glycerin- or glycerol-induced GI irritation.4, 5 Closely monitor patients from birth to 3 months of age for signs and symptoms of GI irritation.4, 5
Safety and effectiveness of IV levothyroxine have not been established in pediatric patients.165, 166
Because of the increased prevalence of cardiovascular disease among elderly patients, oral levothyroxine should be initiated at less than the full replacement dosage in such patients.2, 3, 4, 5, 6, 140, 141 Use caution when administering IV levothyroxine for myxedema coma in elderly patients and monitor for adverse cardiac effects.165, 166 Levothyroxine overtreatment can lead to atrial arrhythmias (including atrial fibrillation) in elderly patients.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
No pharmacokinetic data are available in patients with hepatic impairment.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
No pharmacokinetic data are available in patients with renal impairment.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Adverse reactions associated with oral levothyroxine are primarily those of hyperthyroidism due to therapeutic overdosage, including arrhythmia, myocardial infarction, dyspnea, muscle spasm, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash.2, 3, 4, 5, 6, 140, 141, 142
Adverse reactions associated with IV levothyroxine are also primarily those of hyperthyroidism due to therapeutic overdosage, including fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating, headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia, tremors, muscle weakness, muscle spasm, palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest, dyspnea, diarrhea, vomiting, abdominal cramps, elevations in liver function tests, flushing, and rash.166
Drugs Affecting Hepatic Microsomal Enzymes
Drugs that induce hepatic microsomal enzymes (e.g., phenobarbital, rifampin) may accelerate metabolism of levothyroxine, resulting in increased levothyroxine dosage requirements.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Phenobarbital has been shown to increase levothyroxine metabolism by inducing uridine diphosphate-glucuronosyltransferase (UGT), leading to lower thyroxine (T4) serum levels.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism.2, 3, 4, 5, 6, 140, 141, 142, 166
Drugs Affecting Thyroid Function or Thyroid Function Tests
Many drugs can exert effects on thyroid hormone pharmacokinetics and metabolism, and may alter the therapeutic response to levothyroxine.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 In addition, certain conditions or diseases may cause changes in thyroxine-binding globulin (TBG) concentration, and such possible changes should be considered when interpreting T4 and T3 values.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Pregnancy, infectious hepatitis, and acute intermittent porphyria may increase TBG concentrations.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Nephrosis, severe hypoproteinemia, severe liver disease, and acromegaly decrease TBG concentration.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Estrogens, estrogen-containing oral contraceptives, methadone, fluorouracil, mitotane, and tamoxifen increase serum concentrations of thyroxine-binding globulin (TBG).2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Androgens, usual doses of corticosteroids, asparaginase, and sustained release niacin decrease serum concentrations of TBG.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Consider changes in TBG concentration when interpreting thyroxine (T4) and triiodothyronine (T3) values, and consider measurement of free hormone and/or determination of the free-T4 index.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Carbamazepine, furosemide (at IV dosages exceeding 80 mg), heparin, hydantoins, and nonsteroidal anti-inflammatory agents (NSAIAs, e.g., fenamates) may displace levothyroxine from protein binding sites.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Concomitant use may cause an initial transient increase in concentrations of free T4.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Continued administration results in a decrease in serum T4 and normal free T4 and thyroid-stimulating hormone (TSH) concentrations; therefore, patients are clinically euthyroid.2, 3, 4, 5, 6, 140, 141, 142, 165 Phenytoin and carbamazepine reduce serum protein binding of levothyroxine; total and free T4 may be reduced by 20-40%, but most patients have normal serum TSH levels and are clinically euthyroid.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Monitor thyroid hormone parameters closely when these agents are used concomitantly with levothyroxine.2, 3, 4, 5, 6, 140, 141, 142, 166
Salicylates (at dosages exceeding 2 g daily) inhibit binding of T4 and T3 to TBG and transthyretin.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 An initial increase in serum free T4 is followed by return of free T4 to normal levels with sustained therapeutic serum salicylate concentrations, although total T4 concentrations may decrease by as much as 30%.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Concomitant use of levothyroxine with amiodarone, β-adrenergic blocking agents (e.g., propranolol hydrochloride at dosages exceeding 160 mg daily), or corticosteroids (e.g., dexamethasone at dosages of 4 mg daily or greater) decreases peripheral conversion of T4 to T3, resulting in decreased T3 concentrations.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 However, serum T4 concentrations usually remain within normal range but may occasionally be slightly increased.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 In patients treated with large doses of propranolol hydrochloride (i.e., exceeding 160 mg/day), T3 and T4 concentrations change slightly, TSH levels remain normal, and patients are clinically euthyroid.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 It should be noted that actions of particular β-adrenergic blocking agents may be impaired when the hypothyroid patient is converted to the euthyroid state.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Short-term administration of large doses of corticosteroids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 However, long-term corticosteroid therapy may result in slightly decreased T3 and T4 concentrations because of decreased TBG production.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Biotin supplementation may interfere with thyroid hormone immunoassays that are based on a biotin and streptavidin interaction; this may result in erroneous thyroid hormone test results.142 Stop biotin and biotin-containing supplements for at least 2 days prior to thyroid testing.142
Drugs Affecting Gastric Acidity
Gastric acidity is an essential requirement for adequate levothyroxine absorption.2, 3, 4, 5, 6, 140, 141, 142 Antacids (e.g., aluminum hydroxide, magnesium hydroxide, simethicone), sucralfate, and proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce levothyroxine absorption.3, 4, 5, 6, 140, 141, 142 Gastric acidity may not be as essential for the absorption of levothyroxine administered as Tirosint-SOL®; no clinically significant differences in the pharmacokinetics of this formulation were observed when administered concomitantly with omeprazole.2 Monitor patients appropriately if drugs affecting gastric acidity are used concomitantly with levothyroxine.2, 3, 4, 5, 6, 140, 141, 142 Administer levothyroxine at least 4 hours before or after drugs that are known to interfere with its absorption.2, 3, 4, 5, 6, 140, 141, 142
Levothyroxine may increase response to oral anticoagulant therapy; therefore, a decrease in anticoagulant dosage may be warranted with correction of the hypothyroid state or when the levothyroxine dosage is increased.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Closely monitor coagulation tests and adjust the anticoagulant dosage as needed.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Concomitant use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline [no longer commercially available in the US]) antidepressants and levothyroxine may increase the therapeutic and toxic effects (e.g., increased risk of cardiac arrhythmias and CNS stimulation) of both classes of drugs, possibly secondary to increased receptor sensitivity to catecholamines; onset of action of tricyclic antidepressants may be accelerated.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Concomitant use of sertraline (an SSRI) in patients stabilized on levothyroxine may result in increased levothyroxine requirements.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Administration of levothyroxine to patients with diabetes mellitus may worsen glycemic control and increase the required dosage of insulin or oral antidiabetic agents.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Carefully monitor glycemic control, especially when thyroid therapy is started, changed, or discontinued.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Bile acid sequestrants (e.g., colesevelam, cholestyramine, colestipol) are known to decrease absorption of levothyroxine.2, 3, 4, 5, 6, 140, 141, 142 Administer levothyroxine at least 4 hours prior to these drugs or monitor TSH levels.2, 3, 4, 5, 6, 140, 141, 142
Levothyroxine may reduce the therapeutic effects of digitalis glycosides.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Serum concentrations of digitalis glycosides may decrease when a hypothyroid patient becomes euthyroid, necessitating an increase in digitalis glycoside dosage.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Grapefruit Juice and Other Food Interactions
Grapefruit juice may delay absorption of levothyroxine and reduce its bioavailability.2, 3, 4, 5, 6, 140, 141, 142 Soybean products (e.g., soybeans, soybean flour, infant formula), cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine from the GI tract.2, 3, 4, 5, 6, 140, 141, 142 Evaluate the need for dosage adjustments when regularly administering levothyroxine within 1 hour of foods that may affect the drug's absorption.2, 3, 4, 5, 6, 140, 141, 142
Cation-exchange resins (e.g., sodium polystyrene sulfonate) are known to decrease absorption of levothyroxine.2, 3, 4, 5, 6, 140, 141, 142 Administer levothyroxine at least 4 hours prior to these drugs or monitor TSH levels.2, 3, 4, 5, 6, 140, 141, 142
Concomitant use of ketamine with levothyroxine may produce marked hypertension and tachycardia; closely monitor blood pressure and heart rate.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Concurrent use of orlistat with levothyroxine may reduce the efficacy of levothyroxine by binding and delaying or preventing levothyroxine absorption.2, 3, 4, 5, 6, 140, 141, 142 Monitor patients treated concomitantly with orlistat and levothyroxine for changes in thyroid function.2, 3, 4, 5, 6, 140, 141, 142 Administer levothyroxine at least 4 hours before or after drugs that are known to interfere with its absorption.2, 3, 4, 5, 6, 140, 141, 142
Phosphate binders (e.g., calcium carbonate, ferrous sulfate, sevelamer, lanthanum) may bind to levothyroxine and impair absorption.2, 3, 4, 5, 6, 140, 141, 142 Administer levothyroxine at least 4 hours before or after these agents.2, 3, 4, 5, 6, 140, 141, 142
Concurrent use of sympathomimetic agents may increase the effects of sympathomimetics or levothyroxine.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Concurrent use of tyrosine kinase inhibitors (e.g., imatinib) may cause hypothyroidism; closely monitor TSH levels during concomitant therapy.2, 3, 4, 5, 6, 140, 141, 142
Levothyroxine sodium is a synthetic thyroxine (L -thyroxine; T4) hormone that is chemically identical to the T4 produced in the human thyroid gland.142 Thyroid hormones (T4 and triiodothyronine [T3]) regulate multiple metabolic processes; they are essential for normal growth and development, as well as normal maturation of the CNS and bone.165 Metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates, and lipids.165 Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis.142 These hormones diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA, leading to activation of gene transcription and synthesis of messenger RNA and cytoplasmic proteins.142 The physiologic actions of thyroid hormones are primarily produced by T3; approximately 80% of T3 is derived from the deiodination of T4 in peripheral tissues.142 Levothyroxine sodium exerts the same physiologic effect as endogenous T4. 142
Levothyroxine is variably absorbed from the GI tract (range: 40-80%).2, 3, 4, 5, 6, 140, 141, 142 The majority of levothyroxine is absorbed in the jejunum and upper ileum.2, 3, 4, 5, 6, 140, 141, 142 Levothyroxine absorption is increased in the fasting state and decreased in malabsorption syndromes or in the presence of certain foods (e.g., soybeans, dietary fiber); absorption also may decrease with age.2, 3, 4, 5, 6, 140, 141, 142 Peak therapeutic effects of oral levothyroxine may not be attained for 4-6 weeks.2, 3, 4, 5, 6, 140, 141, 142
The bioavailability of levothyroxine administered as Tirosint-SOL® oral solution relative to levothyroxine oral capsules is approximately 98%.2 No clinically significant difference in levothyroxine pharmacokinetics was observed between Tirosint-SOL® administered 15 minutes or 30 minutes before a high-fat high-calorie meal.2 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 IV levothyroxine sodium is estimated to be 48-74%.165
Circulating thyroid hormones are >99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin, and thyroxine-binding albumin.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Because TBG and thyroxine-binding prealbumin have a higher affinity for T4 compared to T3, T4 has a higher serum level, slower metabolic clearance, and longer half-life than T3.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Only unbound/free hormone is metabolically active.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Thyroid hormones do not readily cross the placental barrier.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
The major pathway of thyroid hormone metabolism is through sequential deiodination.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 The liver is the major site of degradation for both thyroid hormones, with T4 deiodination also occurring at a number of additional sites (including the kidney and other tissues).2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3; these are further deiodinated to diiodothyronine.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut, where they undergo enterohepatic recirculation.2, 3, 4, 5, 6, 140, 141, 142, 165, 166
Thyroid hormones are primarily eliminated by the kidneys.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 Approximately 20% of T4 is eliminated in stool.2, 3, 4, 5, 6, 140, 141, 142 Urinary excretion of T4 decreases with age.2, 3, 4, 5, 6, 140, 141, 142, 165, 166 The usual plasma half-lives of T4 and T3 are 6-7 days and ≤2 days, respectively.2, 3, 4, 5, 6, 140, 141, 142 The plasma half-life of T4 is decreased in patients with hyperthyroidism and increased in those with hypothyroidism.2, 3, 4, 5, 6, 140, 141, 142
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 13 mcg | Tirosint® | |
25 mcg | Tirosint® | |||
37.5 mcg | Tirosint® | |||
44 mcg | Tirosint® | |||
50 mcg | Tirosint® | |||
62.5 mcg | Tirosint® | |||
75 mcg | Tirosint® | |||
88 mcg | Tirosint® | |||
100 mcg | Tirosint® | |||
112 mcg | Tirosint® | |||
125 mcg | Tirosint® | |||
137 mcg | Tirosint® | |||
150 mcg | Tirosint® | |||
175 mcg | Tirosint® | |||
200 mcg | Tirosint® | |||
Solution | 13 mcg/mL | Tirosint-SOL® | ||
20 mcg/mL | Thyquidity® | |||
25 mcg/mL | Tirosint-SOL® | |||
30 mcg/mL | Ermeza® | |||
37.5 mcg/mL | Tirosint-SOL® | |||
44 mcg/mL | Tirosint-SOL® | |||
50 mcg/mL | Tirosint-SOL® | |||
62.5 mcg/mL | Tirosint-SOL® | |||
75 mcg/mL | Tirosint-SOL® | |||
88 mcg/mL | Tirosint-SOL® | |||
100 mcg/mL | Tirosint-SOL® | |||
112 mcg/mL | Tirosint-SOL® | |||
125 mcg/mL | Tirosint-SOL® | |||
137 mcg/mL | Tirosint-SOL® | |||
150 mcg/mL | Tirosint-SOL® | |||
175 mcg/mL | Tirosint-SOL® | |||
200 mcg/mL | Tirosint-SOL® | |||
Tablets | 25 mcg* | Euthyrox® | Provell Pharmaceuticals | |
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Amneal Pharmaceuticals | ||||
50 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
75 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
88 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
100 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
112 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
125 mcg* | Euthryox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
137 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | ||||
150 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
175 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
200 mcg* | Euthyrox® | Provell Pharmaceuticals | ||
Levothyroxine Sodium Tablets | ||||
Levoxyl® (scored) | Pfizer | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
300 mcg* | Levothyroxine Sodium Tablets | |||
Synthroid® (scored) | Abbvie | |||
Unithroid® | Amneal Pharmaceuticals | |||
Parenteral | For injection | 100 mcg* | ||
200 mcg* | Levothyroxine Sodium for Injection | |||
500 mcg* | Levothyroxine Sodium for Injection | |||
Injection | 100 mcg/5 mL (20 mcg/mL)* | Levothyroxine Sodium Injection | ||
200 mcg/5 mL (40 mcg/mL)* | Levothyroxine Sodium Injection | |||
500 mcg/5 mL (100 mcg/mL)* | Levothyroxine Sodium Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
2. IBSA Pharma Inc. Tirosint-Sol (levothyroxine sodium) oral solution prescribing information. Parsippany, NJ; 2022 Oct.
3. IBSA Pharma Inc. Tirosint (levothyroxine sodium) capsules prescribing information. Parsippany, NJ 2024 Jul.
4. Viatris Specialty. Ermeza (levothyroxine sodium) oral solution prescribing information. Morgantown, WV; 2022 Apr.
5. Azurity Pharmaceuticals, Inc. Thyquidity (levothyroxine sodium) oral solution prescribing information. Woburn, MA; 2023 Feb.
6. Provell Pharmaceuticals. Euthyrox (levothyroxine sodium) tablets prescribing information. Honey Brook, PA; 2022 Apr.
140. Amneal Pharmaceuticals. Unithroid® (levothyroxine sodium tablets, USP) prescribing information. Bridgewater, NJ; 2019 Jun.
141. Pfizer Laboratories. Levoxyl® (levothyroxine sodium tablets, USP) prescribing information. New York, NY; 2018 Dec.
142. AbbVie, Inc. Synthroid® (levothyroxine sodium tablets, USP) prescribing information. North Chicago, IL; 2024 Feb.
164. Approved Drug Products with Therapeutic Equivalence Evaluations (Electronic Orange Book). Accessed May 2025. From FDA website. [Web]
165. Fresenius Kabi USA, LLC. Levothyroxine sodium for injection prescribing information. Lake Zurich, IL; 2025 Apr.
166. Fresenius Kabi USA, LLC. Levothyroxine sodium injection prescribing information. Lake Zurich, IL; 2025 Mar.
200. Biondi B, Cooper D. Thyroid hormone therapy for hypothyroidism. Endocrine. 2019;66(1): 18-26.
201. Garber J, Cobin R, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988-1028.
202. Jonklaas J, Bianco A, Bauer A, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24(12): 1670-1751.
203. Persani L, Brabant G, Dattani M, et al. 2018 European Thyroid Association (ETA) guidelines on the diagnosis and management of central hypothyroidism. Eur Thyroid J. 2018;7(5):225-237.
204. Rose S, Wassner A, Wintergerst K, et al. Congenital hypothyroidism: screening and management. Pediatrics. 2023;151(1): e2022060419.
205. Boucai L, Zafereo M, Cabanillas M. Thyroid cancer. JAMA. 2024;331(5):425-435.
206. Haugen B, Alexander E, Bible K, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1-133.
207. Bridwell R, Willis G, Gottlieb M, et al. Decompensated hypothyroidism: a review for the emergency clinician. Am J Emerg Med. 2021; 39:207-212.
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