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Levothyroxine Sodium

Pronunciation

Class: Thyroid Agents
VA Class: HS851
CAS Number: 25416-65-3
Brands: Levothroid, Levoxyl, Synthroid, Unithroid

Introduction

Thyroid agent; sodium salt of thel-isomer of thyroxine (tetraiodothyronine, T4).

Uses for Levothyroxine Sodium

Hypothyroidism

Used orally as replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis.140 141 142 143 161 160 Specific indications include subclinical hypothyroidism and primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism.140 141 142 143 161 160

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Considered drug of choice for the treatment of congenital hypothyroidism (cretinism).a

Used IV for treatment of myxedema coma or other conditions when rapid thyroid replacement is required.140 141 142 155 161 160

Pituitary TSH Suppression

Treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis), and multinodular goiter.140 141 142 161 160

Adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.140 141 142 161 160

Efficacy of TSH suppression for benign nodular disease remains controversial.141 142 160

Other Uses

See Unlabeled Uses under Cautions.

Levothyroxine Sodium Dosage and Administration

General

  • Approved levothyroxine sodium oral preparations157 should be considered therapeutically inequivalent unless equivalence has been established and noted in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).144 The following are considered to be therapeutically equivalent to at least 1 reference listed drug: Levoxyl, Synthroid, Unithroid, and nonproprietary (generic) levothyroxine sodium preparations manufactured by Mylan, Sandoz, or Lannett.162 163 164 Check Orange Book at for more current information on preparations designated therapeutically equivalent by the FDA.

  • Due to narrow therapeutic index, American Thyroid Association (ATA) and American Association of Clinical Endocrinologists (AACE) recommend not to use levothyroxine sodium preparations interchangeably.157 163 When switching preparations (e.g., from brand to generic), pharmacists should notify the patient and prescriber.162 163 In addition, clinicians should measure serum TSH concentration about 4–8 weeks after starting the new preparation and adjust dosage if needed.162 163

  • Initially, monitor response to therapy about every 6–8 weeks.135 140 141 142 Once normalization of thyroid function and serum TSH concentrations has been achieved, patients may be evaluated less frequently (i.e., every 6–12 months).135 However, if dosage of levothyroxine is changed, measure serum TSH concentrations after 8–12 weeks.135 140 141 142 160

Administration

Administer orally or by IV or IM injection.140 141 142 143 161 160 IV is preferred over IM since absorption may be variable following IM administration.a

Oral Administration

Administer orally on an empty stomach, preferably one-half to one hour before breakfast or the first food of the day.140 141 142 143 160 Administer Levoxyl tablets with a full glass of water to avoid choking, gagging, or difficulty in swallowing the tablet.141

In individuals who are unable to swallow intact tablets (e.g., pediatric patients), may crush appropriate dose of levothyroxine tablets and place in a small amount (5–10 mL) of water; immediately administer resultant suspension by spoon or dropper (do not store).140 141 142 152

Foods that decrease absorption of levothyroxine (e.g., soybean infant formula, soybean flour, cotton seed meal) should not be used for administering levothyroxine.140 141 142 160

IV Administration

For solution compatibility information, see Compatibility under Stability.

Reconstitution

Reconstitute Synthroid powder for injection by adding 5 mL of 0.9% sodium chloride injection to vial containing 200 or 500 mcg levothyroxine sodium; shake until clear solution is obtained.161 Resultant solutions contain approximately 40 or 100 mcg/mL, respectively.a

Alternatively, to produce Synthroid solutions containing approximately 100 mcg/mL, add 2 mL 0.9% sodium chloride injection to vial containing 200 mcg.a

Use reconstituted solutions immediately and discard any unused portions; do not admix with IV infusion solutions.161

Dosage

Available as levothyroxine sodium; dosage is expressed in terms of the salt.140 141 142

Adjust dosage carefully according to clinical and laboratory response to treatment.140 141 142 160 Avoid undertreatment or overtreatment.140 141 142 161 160 (See Therapy Monitoring under Cautions.)

Initiate dosage at a lower level in geriatric patients, in patients with functional or ECG evidence of cardiovascular disease, and in patients with severe, long-standing hypothyroidism.145 146 147

Pediatric Patients

Hypothyroidism
Oral

Initiate therapy at full replacement dosages as soon as possible after diagnosis of hypothyroidism to prevent deleterious effects on intellectual and physical growth and development; initiate dosage at a lower level in children with long-standing or severe hypothyroidism.140 141 142 160 The following dosages have been recommended:

Dosage for Management of Hypothyroidism in Pediatric Patients140141142152a160

Age

Daily Dose

0–3 months

10–15 mcg/kg

3–6 months

25–50 mcg or 8–10 mcg/kg

6–12 months

50–75 mcg or 6–8 mcg/kg

1–5 years

75–100 mcg or 5–6 mcg/kg

6–12 years

100–150 mcg or 4–5 mcg/kg

Older than 12 years (growth and puberty incomplete)

>150 mcg or 2–3 mcg/kg

Growth and puberty complete

1.6–1.7 mcg/kg

Alternatively, 25–50 mcg once daily has been recommended for otherwise healthy children <1 year of age; after 1 year of age, children may be given 3–5 mcg/kg daily until the adult dosage of about 150 mcg daily is reached in early or mid-adolescence.a

In neonates at risk of cardiac failure, initiate at a lower dosage (e.g., 25 mcg daily); increase dosage at intervals of 4–6 weeks as needed based on clinical and laboratory response to treatment.140 141 142 143 160 In neonates with very low (<5 mcg/dL) or undetectable serum T4 concentrations, usual initial dosage is 50 mcg daily.140 141 142 152 160

When transient hypothyroidism is suspected, therapy may be temporarily discontinued when the child is older than 3 years of age to reassess the condition.140 141 142 161 160 (See Pediatric Use under Cautions.)

Hyperactivity in an older child may be minimized by initiating therapy at a dosage approximately one-fourth of the recommended full replacement dosage; increase dosage by an amount equal to one-fourth the full recommended replacement dosage at weekly intervals until the full recommended replacement dosage is reached.140 141 142 160

For treatment of severe or long-standing hypothyroidism, usual initial dosage is 25 mcg daily.140 141 142 160 Increase dosage in increments of 25 mcg at intervals of 2–4 weeks until desired response is obtained.140 141 142 160

IV or IM

Replacement therapy: initially about one-half previously established oral dosage.161 Monitor patients closely and adjust dosage according to patient’s tolerance and therapeutic response.161

Adults

Hypothyroidism
Oral

In otherwise healthy individuals <50 years of age and in those >50 years of age who have been recently treated for hyperthyroidism or who have been hypothyroid for only a short time (i.e., several months), usual initial oral dosage (full replacement dosage) is 1.7 mcg/kg daily (e.g., 100–125 mcg daily for a 70-kg adult) given as a single dose.135 140 141 142 143 160 Older patients may require <1 mcg/kg daily.135 140 141 142

Dosages >200 mcg daily seldom required; failure to respond adequately to oral dosages ≥ 300 mcg daily is rare and should prompt reevaluation of the diagnosis, or suggest presence of malabsorption, patient noncompliance, and/or drug interactions.140 141 142 160

For most patients >50 years of age, usual initial dosage is 25–50 mcg daily given as a single dose;135 140 141 142 143 146 147 150 160 increase dosage at intervals of 6–8 weeks.140 141 142 143

For management of severe or long-standing hypothyroidism, usual initial dosage is 12.5–25 mcg daily given as a single dose.140 141 142 160 Increase by increments of 25 mcg at intervals of 2–4 weeks until serum TSH concentrations return to normal;140 141 142 160 some clinicians suggest that dosage be adjusted at intervals of 4–8 weeks.143 145 147

For management of subclinical hypothyroidism (if considered necessary), initiate at lower dosages (e.g., 1 mcg/kg daily).140 141 142 160 If levothyroxine therapy is not initiated, monitor patients annually for changes in clinical status and thyroid laboratory parameters.140 141 142 160

IV and IM

Replacement therapy: about one-half previously established oral dosage.161 Usual parenteral maintenance dosage is 50–100 mcg daily.161

Monitor patients closely and adjust dosage according to patient’s tolerance and therapeutic response.161

Myxedema Coma
IV

In patients who do not have severe cardiovascular disease, usual initial dose is 200–500 mcg;161 some clinicians recommend an initial dose of 100–500 mcg.155 If substantial and progressive improvements have not been achieved, administer 100–300 mcg or greater IV on the second day.161 Lower daily IV dosages should then be administered as needed until patient’s condition stabilizes and drug can be given orally.161

Pituitary TSH Suppression

Individualize dosage based on patient characteristics and nature of the disease.141 142 160 Target level for TSH suppression in management of well-differentiated thyroid cancer and thyroid nodules not established.141 142 160

Thyroid Cancer
Oral

Dosages >2 mcg/kg daily given as a single dose usually required to suppress TSH concentrations to <0.1 mU/L.140 141 142 160 In patients with high-risk tumors, target level for TSH suppression may be <0.01 mU/L.141 160

Benign Nodules or Nontoxic Multinodular Goiter
Oral

Suppress TSH concentrations to 0.1–0.5 mU/L for nodules and to 0.5–1 mU/L for multinodular goiter.140 142 143 160

Special Populations

Patients with Cardiovascular Disease

Hypothyroidism

Initiate therapy at lower doses than those recommended in patients without cardiovascular disease.140 141 142 161 160 For patients <50 years of age with underlying cardiovascular disease, usual initial dosage is 25–50 mcg daily given as a single dose;135 140 141 142 143 146 147 150 160 increase dosage at intervals of 6–8 weeks.140 141 142 143

If cardiac symptoms develop or worsen, reduce dosage or withhold therapy for 1 week and then cautiously restart therapy at a lower dose.140 141 142 161 160

Myxedema Coma
IV

If levothyroxine therapy is clinically indicated, smaller initial IV doses may be necessary.161 Consider risks of adverse cardiovascular effects associated with sudden IV administration of large doses of levothyroxine sodium against risks of withholding therapy.161

Geriatric Patients

Hypothyroidism

Initiate therapy at lower doses than those recommended in younger patients.140 141 142 161 160

In geriatric patients with underlying cardiovascular disease, usual initial dosage is 12.5–25 mcg daily; increase dosage by increments of 12.5–25 mcg at intervals of 4–6 weeks until patient becomes euthyroid and serum TSH concentrations return to normal.140 141 142 160 If cardiac symptoms develop or worsen, reduce dosage or withhold therapy for 1 week and then cautiously restart therapy at a lower dose.140 141 142 161 160

Myxedema Coma

Reduced initial dose may be appropriate in geriatric patients.155 161

Cautions for Levothyroxine Sodium

Contraindications

  • Untreated subclinical (suppressed serum TSH concentrations with normal T3 [triiodothyronine] and T4 concentrations) or overt thyrotoxicosis of any etiology.140 141 142 160 161

  • AMI.140 141 142 161 160

  • Untreated adrenal insufficiency.140 141 142 161 160

  • Known hypersensitivity to any ingredient in the formulation.140 141 142 161 160 (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Unlabeled Uses

Should not be used for the treatment of obesity or for weight loss either alone or with other therapeutic agents.140 141 142 161 160 In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.140 141 142 161 160 Larger doses may produce serious or life-threatening toxicity, particularly when given in conjunction with sympathomimetic amines (e.g., anorectic agents).140 141 142 161 160

Should not be used in the treatment of male or female infertility unless this condition is associated with hypothyroidism.140 141 142 161 160

Thyrotoxicosis

Because of risk of precipitating overt thyrotoxicosis, levothyroxine is contraindicated in patients with nontoxic diffuse goiter or nodular thyroid disease (particularly geriatric patients or those with underlying cardiovascular disease) in whom serum TSH level is already suppressed.141 142 161 160

If serum TSH level is not suppressed, use with caution and monitor clinical (e.g., adverse cardiovascular effects) and laboratory (i.e., thyroid function) parameters for evidence of hyperthyroidism.141 142 161 160

Sensitivity Reactions

Hypersensitivity to levothyroxine is not known to occur.140 141 142 161 160 However, hypersensitivity reactions to inactive ingredients of thyroid hormone products have been reported and include urticaria, pruritus, rash, flushing, angioedema, abdominal pain, nausea, vomiting, diarrhea, fever, arthralgia, serum sickness, and wheezing.140 141 142 161 160

Major Toxicities

Effects on Bone Mineral Density

In women, long-term therapy has been associated with decreased bone mineral density, especially in postmenopausal women receiving greater than replacement doses or in women who are receiving suppressive doses.140 141 142 161 160 Use lowest dose necessary to achieve desired clinical and biochemical response.140 141 142 161 160

GI Effects

Choking, gagging, dysphagia, or lodging of a tablet in the throat reported with Levoxyl, particularly when administered without water.141 Administer Levoxyl tablets with a full glass of water.141

General Precautions

Therapy Monitoring

Levothyroxine has a narrow therapeutic index.140 141 142 161 160 Avoid undertreatment or overtreatment, which may result in adverse effects on growth and development in pediatric patients, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, GI function, and glucose and lipid metabolism.140 141 142 161 160

Periodically perform appropriate laboratory tests (e.g., serum TSH, total or free T4) and clinical evaluations to monitor adequacy of therapy.140 141 142 161 160

Preexisting Cardiovascular Disease

Use with caution.140 141 142 161 160 (See Patients with Cardiovascular Disease under Dosage and Administration.) Patients with CHD should be monitored closely during surgical procedures due to increased risk of arrhythmias.140 141 142 161 160

Associated Endocrine Disorders

In patients with secondary or tertiary hypothyroidism, consider possibility of additional hypothalamic/pituitary hormone deficiencies and treat if diagnosed.140 141 142 161 160

Chronic autoimmune thyroiditis may occur in association with other autoimmune disorders (e.g., adrenal insufficiency, pernicious anemia, and insulin-dependent diabetes mellitus).140 141 142 161 160

Patients with concomitant adrenal insufficiency should be treated with replacement glucocorticoids prior to initiation of levothyroxine.140 141 142 161 160 Failure to do so may precipitate an acute adrenal crisis due to increased metabolic clearance of glucocorticoids when levothyroxine is initiated.140 141 142 161 160

Patients with diabetes mellitus may require increased dosages of antidiabetic agents when treated with levothyroxine.140 141 142 161 160

Lactose Intolerance

Lactose is used in manufacture of Synthroid and Unithroid tablets.140 142

Specific Populations

Pregnancy

Category A.140 141 142 161 160

During pregnancy, serum T4 levels may decrease and serum TSH levels increase to values outside the normal range.140 141 142 161 160 Elevations in serum TSH may occur at 4 weeks gestation; monitor TSH levels during each trimester and adjust levothyroxine dosage accordingly.140 141 142 161 160 Reduce dosage to pre-pregnancy level immediately after delivery, since postpartum TSH concentrations are similar to preconception levels; measure serum TSH concentrations 6–8 weeks postpartum.140 141 142 161 160

Lactation

Although thyroid hormones are distributed minimally into human milk, exercise caution when administering to a nursing woman.140 141 142 161 160 However, adequate replacement dosages generally are needed to maintain normal lactation.140 141 142 161 160

Pediatric Use

The goal of treatment in pediatric patients with hypothyroidism is to achieve and maintain normal intellectual and physical growth and development.140 141 142 161 160 Initiate therapy immediately upon diagnosis and maintain for life, unless transient hypothyroidism is suspected.140 141 142 161 160

Neonates with suspected hypothyroidism should receive thyroid agent therapy pending results of confirmative tests. If a positive diagnosis cannot be made on the basis of laboratory findings but there is a strong clinical suspicion of congenital hypothyroidism, initiate replacement therapy to achieve euthyroidism until the child is 1–2 years of age. During first 2 weeks of therapy, closely monitor infants for cardiac overload, arrhythmias, and aspiration resulting from avid suckling.140 141 142 161 160 Evaluate infant’s clinical response to therapy about 6 weeks after initiation of levothyroxine and at least at 6 and 12 months of age and yearly thereafter.

When transient hypothyroidism is suspected, temporarily discontinue therapy for 4–8 weeks to reassess the condition when the child is >3 years of age.140 141 142 161 160 If the diagnosis of permanent hypothyroidism is confirmed, reinstitute full replacement therapy.140 141 142 161 160 However, if serum concentrations of T4 and TSH are normal, discontinue levothyroxine and monitor carefully; repeat thyroid function tests if manifestations of hypothyroidism develop.140 141 142 161 160

In pediatric patients with transient severe hypothyroidism, reduce replacement dose by half for 30 days.140 141 142 161 160 If, after 30 days, serum TSH >20 mU/L, consider the hypothyroidism permanent and reinstitute full replacement therapy.140 141 142 161 160 However, if serum TSH ≤ 20 mU/L, temporarily discontinue levothyroxine for 30 days, then repeat serum T4 and TSH measurements.140 141 142 161 160 Reinstitute or discontinue replacement therapy based on laboratory findings.140 141 142 161 160

Monitor patients closely to avoid undertreatment or overtreatment.140 141 142 161 160 Undertreatment may result in impaired intellectual development, poor school performance (due to impaired concentration and slowed mentation), and reduced adult height.140 141 142 161 160 Overtreatment may result in craniosynostosis in infants and accelerate aging of bones, resulting in premature epiphyseal closure and compromised adult stature.140 141 142 161 160

Treated children may manifest a period of catch-up growth, which may be adequate in some cases to achieve normal adult height. In children with severe or long-standing hypothyroidism, catch-up growth may not be adequate to achieve normal adult height.140 141 142 161 160

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine.140 141 142 161 160

Geriatric Use

Because of the increased risk of cardiovascular disease among geriatric patients, levothyroxine therapy should not be initiated at the full replacement dose.140 141 142 161 160

Common Adverse Effects

Adverse reactions result from overdosage and resemble manifestations of hyperthyroidism, including fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating, headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia, tremor, muscle weakness, palpitations, tachycardia, arrhythmias, increased heart rate and BP, heart failure, angina, AMI, cardiac arrest, dyspnea, diarrhea, vomiting, abdominal cramps, elevations in liver function tests, hair loss, flushing, decreased bone mineral density, menstrual irregularities, and impaired fertility.141 142 161 160

Interactions for Levothyroxine Sodium

Drugs Affecting Hepatic Microsomal Enzymes

Potential increased levothyroxine metabolism and decreased plasma levothyroxine concentrations with drugs that induce general hepatic metabolic activity resulting in increased levothyroxine dosage requirements.141 142 161 160

Drugs That May Decrease T4 5’-Deiodinase Activity

Inhibitors of T4 5’-deiodinase decrease peripheral conversion of T4 to T3, resulting in decreased T3 concentrations.140 141 142 161 160 However, serum T4 concentrations usually remain within normal range but may occasionally be slightly increased.140 141 142 161 160

Specific Drugs and Foods

Drug or Food

Interaction

Comment

Amiodarone

Decreased metabolism of T4 to T3140 141 142 161 160

Anticoagulants, oral (e.g., coumarins)

Potentiation of anticoagulant activity140 141 142 161 160

Carefully monitor PT and adjust anticoagulant dosage accordingly140 141 142 161 160

Antidepressants (tricyclics, tetracyclics, SSRIs)

Increased risk of cardiac arrhythmias and CNS stimulation when used with tricyclics or tetracyclics140 141 142 161 160

Faster onset of action of tricyclics140 141 142 161 160

Sertraline may increase levothyroxine requirements140 141 142 161 160

Antidiabetic agents (biguanides, meglitinides, sulfonylureas, thiazolidediones, insulin)

Levothyroxine may cause increased antidiabetic agent or insulin requirements140 141 142 161 160

Carefully monitor diabetic control, especially when thyroid therapy is initiated, changed, or discontinued140 141 142 161 160

β-Adrenergic blocking agents (e.g., propranolol hydrochloride dosages >160 mg daily)

Decreased metabolism of T4 to T3140 141 142 161 160

Impaired antihypertensive effects when hypothyroid patient is converted to euthyroid state140 141 142 161 160

Bile acid sequestrants (e.g., cholestyramine, colestipol)

Delayed or impaired levothyroxine absorption140 141 142 161 160

Administer levothyroxine at least 4 hours apart from these agents140 141 142 154 161 160

Carbamazepine

Potential increased levothyroxine metabolism140 141 142 161 160

Reduced levothyroxine serum protein binding140 141 142 161 160

May require levothyroxine dosage increase140 141 142 161 160

Cardiac glycosides

Decreased serum digitalis glycoside concentrations in patients with hyperthyroidism or in patients with hypothyroidism in whom a euthyroid state has been achieved; potential for reduced therapeutic effects of digitalis glycosides with levothyroxine140 141 142 161 160

May need to increase dosage of digitalis glycoside when hypothyroidism has been corrected140 141 142 161 160

Corticosteroids (e.g., dexamethasone at dosages >4 mg daily)

Decreased metabolism of T4 to T3140 141 142 161 160 . Short-term administration of large doses of corticosteroids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels140 141 142 161 160

Ferrous sulfate

Delayed or impaired levothyroxine absorption140 141 142 161 160

Administer levothyroxine at least 4 hours apart from this agent140 141 142 154 161 160

Food with large amounts of fiber (e.g., cotton seed meal, infant soybean formula, soybean flour, walnuts)

Delayed or impaired levothyroxine absorption140 141 142 161 160

Fusosemide (at IV dosages >80 mg)

Concomitant use with levothyroxine produces transient increases in serum free T4 concentrations; continued administration results in a decrease in serum T4 and normal free T4 and TSH concentrations, and therefore, patients are clinically euthyroid140 141 142 161 160

GI drugs (e.g., antacids [aluminum hydroxide, magnesium hydroxide, calcium carbonate], simethicone, sucralfate)

Delayed or impaired levothyroxine absorption140 141 142 161 160

Administer levothyroxine at least 4 hours apart from these agents140 141 142 154 161 160

Growth hormones (e.g., somatropin)

Excessive levothyroxine use with growth hormones may accelerate epiphyseal closure; however, untreated hypothyroidism may interfere with growth response to growth hormone140 141 142 161 160

Heparin

Concomitant use with levothyroxine produces transient increases in serum free T4 concentrations; continued administration results in a decrease in serum T4 and normal free T4 and TSH concentrations, and therefore, patients are clinically euthyroid140 141 142 161 160

Hydantoins (e.g., phenytoin)

Potential increased levothyroxine metabolism140 141 142 161 160

Reduced levothyroxine serum protein binding140 141 142 161 160

May require levothyroxine dosage increase140 141 142 161 160

Ketamine

Risk of marked hypertension and tachycardia140 141 142 161 160

Use with caution140 141 142 161 160

NSAIAs (e.g., fenamates, phenylbutazone)

Concomitant use with levothyroxine produces transient increases in serum free T4 concentrations; continued administration results in a decrease in serum T4 and normal free T4 and TSH concentrations, and therefore, patients are clinically euthyroid140 141 142 161 160

Phenobarbital

Potential increased levothyroxine metabolism 140 141 142 161 160

May require levothyroxine dosage increase140 141 142 161 160

Propylthiouracil

Decreased metabolism of T4 to T3140 141 142 161 160

Radiographic agents

Reduced uptake of 123I, 131I, and99mTc140 141 142 161 160

Rifampin

Potential increased levothyroxine metabolism 140 141 142 161 160

May require levothyroxine dosage increase140 141 142 161 160

Salicylates (dosages >2 g daily)

Inhibit binding of T4 and T3 to TBG and transthyretin; initially increases serum free T4 followed by return to normal concentrations with sustained therapeutic serum salicylate concentrations, although total T4 concentrations may decrease by as much as 30%140 141 142 161 160

Sodium polystyrene sulfonate

Delayed or impaired levothyroxine absorption140 141 142 161 160

Administer levothyroxine at least 4 hours apart from this agent140 141 142 154 161 160

Sympathomimetic agents

Potentiation of sympathomimetic or thyroid effects; increased risk of coronary insufficiency in patients with CHD140 141 142 161 160

Xanthine derivatives (e.g., theophylline)

Clearance of xanthine derivatives may be decreased in hypothyroid patients but returns to normal when the euthyroid state is achieved140 141 142 161 160

Drugs Affecting Thyroid Function or Thyroid Function Tests

Various drugs or concomitant medical conditions (e.g., pregnancy, infectious hepatitis) may adversely affect thyroid function (e.g., alter endogenous thyroid hormone secretion, reduce TSH secretion) resulting in hypothyroidism or hyperthyroidism or interfere with laboratory tests used to assess thyroid function.140 141 142 161 160 Consult specialized references for information.

Some drugs may affect transport of thyroid hormones (T3, T4, levothyroxine) by affecting serum thyroxine-binding globulin (TBG) concentrations.140 141 142 161 160 However, free T4 concentrations may remain normal and the patient may remain euthyroid.140 141 142 161 160 Monitor therapy and adjust levothyroxine dosages as necessary.140 141 142 161 160

Drugs Affecting Thyroxine Binding Globulin Concentration140 141 142 161 160

The following drugs may increase serum TBG concentrations:

  • Estrogens, oral (including estrogen-containing oral contraceptives)

  • Fluorouracil

  • Methadone

  • Mitotane

  • Tamoxifen

The following drugs may decrease serum TBG concentrations:

  • Androgens

  • Asparaginase

  • Glucocorticoids

  • Niacin (sustained-release)

Levothyroxine Sodium Pharmacokinetics

Absorption

Bioavailability

Variably absorbed from the GI tract (range: 40–80%).137 140 141 142 143 159 160

Extent of absorption is increased in the fasting state and decreased in malabsorption states (e.g., sprue); absorption also may decrease with age.140 141 142 140 141 142

Absorption is variable following IM administration.

Currently approved levothyroxine preparations should be considered therapeutically inequivalent unless equivalency has been established and noted in the FDA’s Approved Drug Products with Therapeutic Equivalency Evaluations (Orange Book).144

Onset

Due to the long half-life, peak therapeutic effects may not be attained for 4–6 weeks.140 141 142 161 160

Food

Infant soybean formula, soybean flour, cotton seed meal, walnuts, and foods containing large amounts of fiber may decrease absorption of levothyroxine.139 140 141 142

Distribution

Extent

Thyroid hormones do not readily cross the placenta; however, some transfer does occur, as evidenced by levels in cord blood of athyrotic fetuses being approximately one-third maternal levels.140 141 142 161 160

Minimally distributed into breast milk.140 141 142 161 160

Plasma Protein Binding

Circulating thyroid hormones are >99% bound to plasma proteins, including TBG, thyroxine-binding prealbumin (TBPA), and albumin.140 141 142 161 160 Only unbound hormone is metabolically active.140 141 142 161 160

Elimination

Metabolism

T4 and T3 are metabolized principally in the liver through sequential deiodination.140 141 142 161 160 Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3).140 141 142 161 160 T3 and rT3 are further deiodinated to diiodothyronine.140 141 142 161 160 Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.140 141 142 161 160

Elimination Route

Primarily eliminated by the kidneys.140 141 142 161 160 A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces.140 141 142 161 160 Approximately 20% of T4 is eliminated in the stool.140 141 142 161 160 Urinary excretion of T4 decreases with age.140 141 142 161 160

Half-life

6–7 days for T4 (3–4 days in hyperthyroidism; 9–10 days in hypothyroidism).140 141 142 161 160

≤ 2 days for T3.140 141 142 161 160

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).140 141 142 161 160 Protect from heat, moisture, and light.140 141 142 161 160

Parenteral

Powder for Injection

25°C (may be exposed to 15–30°C).161

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Reconstituted solution should not be admixed with IV infusion solutions.161

Parenteral

Solution Compatibility161

Compatible

0.9% sodium chloride

Actions

  • Thyroid hormones (tetraiodothyronine [thyroxine, T4] and triiodothyronine [T3]) regulate multiple metabolic processes, including augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates, and lipids.140 141 142 161 160

  • Thyroid hormones also play an essential role in normal growth and development and normal maturation of the CNS and bone.140 141 142 161 160 The protein anabolic effects of thyroid hormones are essential for normal growth and development.140 141 142 161 160

  • The physiologic actions of thyroid hormones are produced predominantly by T3, most of which (approximately 80%) is derived from T4 by deiodination in peripheral tissues.140 141 142 161 160

  • T3 is 4 times more potent than T4.140 141 142 161 160 The ratio of T4 to T3 in thyroglobulin is 10–20 to 1.140 141 142 161 160

Advice to Patients

  • Importance of understanding the need to continue levothyroxine therapy for life, unless transient hypothyroidism is suspected.140 141 142 161 160

  • Importance of taking levothyroxine exactly as prescribed;140 141 142 161 160 take Levoxyl with a full glass of water.141 Do not alter regimen or discontinue therapy unless directed by a clinician.140 141 142 161 160

  • Risk of transient hair loss.140 141 142 161 160 Importance of immediately informing a clinician if rapid or irregular heartbeat, chest pain, shortness of breath, leg cramps, headache, nervousness, irritability, sleeplessness, tremors, change in appetite, weight gain or loss, vomiting, diarrhea, excessive sweating, heat intolerance, fever, changes in menstrual periods, hives or skin rash, or any other unusual medical event occurs.140 141 142 161 160

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease, diabetes mellitus, clotting disorders, adrenal or pituitary gland problems).140 141 142 161 160

  • In patients with diabetes mellitus, importance of monitoring blood and/or urinary glucose levels and immediately reporting any changes to a clinician.140 141 142 161 160 In patients receiving concomitant anticoagulant therapy, importance of monitoring clotting status frequently.140 141 142 161 160

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.140 141 142 161 160 Dosage may need to be increased during pregnancy.140 141 142 161 160

  • Importance of informing physician or dentist of current levothyroxine therapy prior to any surgery.140 141 142 161 160

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Levothyroxine Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

50 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

75 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

88 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

100 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

112 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

125 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

137 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

150 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

175 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

200 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

300 mcg*

Levothroid

Forest

Levothyroxine Sodium (scored)

Lannett, Mylan, Sandoz

Levoxyl (scored)

Monarch

Synthroid (scored)

Abbott

Unithroid

Watson

Parenteral

For injection

200 mcg*

Levothyroxine Sodium for Injection

American Pharmaceutical Partners, Bedford

Synthroid

Abbott

500 mcg*

Levothyroxine Sodium for Injection

American Pharmaceutical Partners, Bedford

Synthroid

Abbott

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Levothroid 112MCG Tablets (FOREST): 30/$15.99 or 90/$25.97

Levothroid 125MCG Tablets (FOREST): 30/$15.99 or 90/$29.97

Levothroid 137MCG Tablets (FOREST): 30/$14.99 or 90/$28.97

Levothroid 150MCG Tablets (FOREST): 30/$15.99 or 60/$23.98

Levothroid 175MCG Tablets (FOREST): 30/$16.99 or 90/$29.97

Levothroid 200MCG Tablets (FOREST): 30/$16.99 or 90/$35.97

Levothroid 25MCG Tablets (FOREST): 30/$14.99 or 90/$21.97

Levothroid 300MCG Tablets (FOREST): 30/$20.99 or 90/$47.98

Levothroid 50MCG Tablets (FOREST): 30/$14.99 or 60/$19.97

Levothroid 75MCG Tablets (FOREST): 30/$14.99 or 60/$20.98

Levothroid 88MCG Tablets (FOREST): 30/$14.99 or 90/$25.97

Levothyroxine Sodium 100MCG Tablets (SANDOZ): 30/$14.99 or 90/$25.97

Levothyroxine Sodium 112MCG Tablets (MYLAN): 30/$15.99 or 60/$25.98

Levothyroxine Sodium 125MCG Tablets (LANNETT): 30/$15.99 or 60/$20.98

Levothyroxine Sodium 137MCG Tablets (LANNETT): 30/$13.99 or 90/$33.98

Levothyroxine Sodium 150MCG Tablets (LANNETT): 30/$14.99 or 60/$19.98

Levothyroxine Sodium 175MCG Tablets (LANNETT): 30/$14.99 or 60/$24.98

Levothyroxine Sodium 200MCG Tablets (LANNETT): 30/$16.99 or 90/$38.97

Levothyroxine Sodium 25MCG Tablets (MYLAN): 30/$13.99 or 60/$19.98

Levothyroxine Sodium 300MCG Tablets (MYLAN): 30/$20.99 or 90/$42.97

Levothyroxine Sodium 50MCG Tablets (LANNETT): 30/$13.99 or 60/$17.98

Levothyroxine Sodium 75MCG Tablets (LANNETT): 30/$14.99 or 60/$19.98

Levothyroxine Sodium 88MCG Tablets (MYLAN): 30/$14.99 or 90/$29.97

Levoxyl 100MCG Tablets (KING PHARMA): 30/$22.99 or 90/$47.97

Levoxyl 112MCG Tablets (KING PHARMA): 30/$23.99 or 90/$49.97

Levoxyl 125MCG Tablets (KING PHARMA): 30/$24.99 or 90/$53.97

Levoxyl 137MCG Tablets (KING PHARMA): 30/$26.99 or 90/$57.97

Levoxyl 150MCG Tablets (KING PHARMA): 30/$22.99 or 90/$49.97

Levoxyl 175MCG Tablets (KING PHARMA): 30/$28.99 or 90/$64.97

Levoxyl 200MCG Tablets (KING PHARMA): 30/$28.99 or 90/$65.97

Levoxyl 25MCG Tablets (KING PHARMA): 30/$20.99 or 90/$39.97

Levoxyl 50MCG Tablets (KING PHARMA): 30/$22.99 or 60/$34.97

Levoxyl 75MCG Tablets (KING PHARMA): 30/$21.99 or 90/$41.97

Levoxyl 88MCG Tablets (KING PHARMA): 30/$20.99 or 90/$41.97

Synthroid 100MCG Tablets (ABBOTT): 30/$28.99 or 90/$64.97

Synthroid 112MCG Tablets (ABBOTT): 30/$30.99 or 90/$74.97

Synthroid 125MCG Tablets (ABBOTT): 30/$32.99 or 90/$78.97

Synthroid 137MCG Tablets (ABBOTT): 30/$32.99 or 90/$98.97

Synthroid 150MCG Tablets (ABBOTT): 30/$33.99 or 90/$75.97

Synthroid 175MCG Tablets (ABBOTT): 30/$35.99 or 90/$84.97

Synthroid 200MCG Tablets (ABBOTT): 30/$35.99 or 90/$84.97

Synthroid 25MCG Tablets (ABBOTT): 30/$24.99 or 90/$52.97

Synthroid 300MCG Tablets (ABBOTT): 30/$44.99 or 90/$115.97

Synthroid 50MCG Tablets (ABBOTT): 30/$25.99 or 90/$57.97

Synthroid 75MCG Tablets (ABBOTT): 30/$27.99 or 90/$61.97

Synthroid 88MCG Tablets (ABBOTT): 30/$28.99 or 90/$64.97

Unithroid 100MCG Tablets (LANNETT): 30/$17.99 or 90/$35.97

Unithroid 112MCG Tablets (LANNETT): 30/$19.99 or 90/$39.97

Unithroid 125MCG Tablets (LANNETT): 30/$19.99 or 90/$39.97

Unithroid 150MCG Tablets (LANNETT): 30/$20.99 or 60/$30.97

Unithroid 200MCG Tablets (LANNETT): 30/$25.99 or 60/$39.97

Unithroid 25MCG Tablets (LANNETT): 30/$16.99 or 60/$25.97

Unithroid 50MCG Tablets (LANNETT): 30/$17.99 or 90/$31.97

Unithroid 75MCG Tablets (LANNETT): 30/$18.99 or 90/$35.97

Unithroid 88MCG Tablets (LANNETT): 30/$18.99 or 60/$29.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

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a. AHFS drug information 2003. McEvoy GK, ed. Levothyroxine Sodium. Bethesda, MD: American Society of Health-System Pharmacists; 2003:3067-70.

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