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Cautions

Contraindications

• Untreated subclinical (suppressed serum TSH concentrations with normal T₃ [triiodothyronine] and T₄ concentrations) or overt thyrotoxicosis of any etiology.
• AMI.
• Untreated adrenal insufficiency.
• Known hypersensitivity to any ingredient in the formulation. (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. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or life-threatening toxicity, particularly when given in conjunction with sympathomimetic amines (e.g., anorectic agents).

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

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.

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.

Sensitivity Reactions

Hypersensitivity to levothyroxine is not known to occur. 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.

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. Use lowest dose necessary to achieve desired clinical and biochemical response.

GI Effects

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

General Precautions

Therapy Monitoring

Levothyroxine has a narrow therapeutic index. 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.

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

Preexisting Cardiovascular Disease

Use with caution. (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.

Associated Endocrine Disorders

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

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

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

Patients with diabetes mellitus may require increased dosages of antidiabetic agents when treated with levothyroxine.

Lactose Intolerance

Lactose is used in manufacture of Synthroid^® and Unithroid^® tablets.

Specific Populations

Pregnancy

Category A.

During pregnancy, serum T₄ levels may decrease and serum TSH levels increase to values outside the normal range. Elevations in serum TSH may occur at 4 weeks gestation; monitor TSH levels during each trimester and adjust levothyroxine dosage accordingly. 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.

Lactation

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

Pediatric Use

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

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. 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. If the diagnosis of permanent hypothyroidism is confirmed, reinstitute full replacement therapy. However, if serum concentrations of T₄ and TSH are normal, discontinue levothyroxine and monitor carefully; repeat thyroid function tests if manifestations of hypothyroidism develop.

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

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

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.

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine.

Geriatric Use

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

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.