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Uses

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. Specific indications include subclinical hypothyroidism and primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism.

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

Used IV for treatment of myxedema coma or other conditions when rapid thyroid replacement is required.

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.

Adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

Efficacy of TSH suppression for benign nodular disease remains controversial.

Other Uses

See Unlabeled Uses under Cautions.

Dosage and Administration

General

• Approved levothyroxine sodium oral preparations 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). 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. Check Orange Book at http://www.fda.gov/cder/ob 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. When switching preparations (e.g., from brand to generic), pharmacists should notify the patient and prescriber. In addition, clinicians should measure serum TSH concentration about 4–8 weeks after starting the new preparation and adjust dosage if needed.
• Initially, monitor response to therapy about every 6–8 weeks. Once normalization of thyroid function and serum TSH concentrations has been achieved, patients may be evaluated less frequently (i.e., every 6–12 months). However, if dosage of levothyroxine is changed, measure serum TSH concentrations after 8–12 weeks.

Administration

Administer orally or by IV or IM injection. IV is preferred over IM since absorption may be variable following IM administration.

Oral Administration

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

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).

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

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. Resultant solutions contain approximately 40 or 100 mcg/mL, respectively.

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

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

Dosage

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

Adjust dosage carefully according to clinical and laboratory response to treatment. Avoid undertreatment or overtreatment. (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.

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. The following dosages have been recommended:

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.

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. In neonates with very low (<5 mcg/dL) or undetectable serum T₄ concentrations, usual initial dosage is 50 mcg daily.

When transient hypothyroidism is suspected, therapy may be temporarily discontinued when the child is older than 3 years of age to reassess the condition. (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.

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

IV or IM

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

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. Older patients may require <1 mcg/kg daily.

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.

For most patients >50 years of age, usual initial dosage is 25–50 mcg daily given as a single dose; increase dosage at intervals of 6–8 weeks.

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

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

IV and IM

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

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

Myxedema Coma

IV

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

Pituitary TSH Suppression

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

Thyroid Cancer

Oral

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

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.

Special Populations

Patients with Cardiovascular Disease

Hypothyroidism

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

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

Myxedema Coma

IV

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

Geriatric Patients

Hypothyroidism

Initiate therapy at lower doses than those recommended in younger patients.

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

Myxedema Coma

Reduced initial dose may be appropriate in geriatric patients.