Today I would like to write something about levothyroxine. My hospital uses levothyroxine often. Everyday there are lots of patients prescribed with levothyroxine. I do believe it is necessary to write below for education, which is not only for patients but also providers. The reference I use comes from U.S. FDA’s official drug information database.

Indications and Usage

Levothyroxine sodium is used for the following indications:

Hypothyroidism – 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: primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism. Primary hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter.

Pituitary TSH Suppression – In the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis, multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

Contraindications

Levothyroxine is contraindicated in patients with untreated subclinical (suppressed serum TSH level with normal T3 and T4 levels) or overt thyrotoxicosis of any etiology and in patients with acute myocardial infarction. Levothyroxine is contraindicated in patients with uncorrected adrenal insufficiency since thyroid hormones may precipitate an acute adrenal crisis by increasing the metabolic clearance of glucocorticoids. Finally, levothyroxine is contraindicated in patients with hypersensitivity to any of the inactive ingredients in levothyroxine.

Dosage and Administration

  • The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state.
  • The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue.

To acheive the two goals above, it depends on variety of factors including the patient’s age, body weight, cardiovascular status, concomitant medical conditions (e.g., pregnancy, concomitant medications, and the specific nature of the condition being treated). As a result Dosing must be individualized and adjustments made based on periodic assessment of the patient’s clinical response and laboratory parameters.

Levothyroxine sodium tablets are administered as a single daily dose.

Table 1 The Indication and Dosages of Levothyroxine

Indication and Usage Dosage
1 Hypothyroidism Individuals who are at low risk of coronary artery disease Starting at 1.7 mcg/kg/day (Full dose). Adjusting dosage in 12.5-25 mcg increments until clinically euthyroid and serum TSH has normalized.
If myxedema coma, administer intravenously rather than orally Individuals older than 50 yrs or under 50 yrs with underlying cardiac disease Starting from 25-50 mcg/day, with increments of 12.5-25 mcg/day at 6-8 week intervals until clinical euthyroid and the serum TSH has normalized
Elderly individuals Starting from 12.5-25 mcg/day, with increments of 12.5-25 mcg/day at 4-6 week intervals until clinical euthyroid and the serum TSH has normalized
Individuals with severe hypothyroidism Starting from 12.5-25 mcg/day, with increments of 25 mcg/day at 2-4 week intervals until clinical euthyroid and the serum TSH has normalized
Secondary or tertiary hypothyroidism Dosage as above but titrated until clinically euthyroid and serum free-T4 level is restored to the upper half of the normal range
2 TSH Suppression – various types of euthyroid goiters and thyroid cancer Well-differentiated thyroid cancer > 2 mcg/kg/day (Target: TSH suppressed to <0.1 mU/L)
Contraindicated if the serum TSH is already suppressed Well-differentiated thyroid cancer (high risk) Target: TSH suppressed to <0.01 mU/L
Benign nodules and nontoxic multinodular goiter (controversial) Target: TSH suppressed to between 0.1 to either 0.5 or 1.0 mU/L

 

The adequacy of therapy is determined by periodic assessment of appropriate laboratory tests and clinical evaluation. In adult patients with primary (thyroidal) hypothyroidism, serum TSH levels alone may be used to monitor therapy. The frequence of TSH monitoring during levothyroxine dose titration depends on the clinical situation but it is generally recommended at 6-8 week intervals until normalization.

Monitor

For patients who have recently initiated levothyroxine therapy and whose serum TSH has normalized or in patients who have had their dosage of levothyroxine changed, the serum TSH concentration should be measured after 8-12 weeks.

When the optimum replacement dose has been attained, clinical and biochemical monitoring may be performed every 6-12 months, depending on the clinical situation, and whenever there is a change in the patient’s status.

As mentioned in the table above, the therapy targets are list there.

Interactions

Levothyroxine do has a lot of drug interactions. Besure to contact ID pharmacist for consultation. Levothyroxine sodium tablets should be taken at least 4 hours apart from drugs that are known to interfere with its absorption.

Consumption of certain foods may affect levothyroxine absorption thereby necessitating adjustments in dosing. Soybean flour, cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine for the gastrointestinal tract. As a result levothyroxine sodium tablets are administered as a single daily dose, preferably one-half to one hour before breakfast due to that the absorption of levothyroxine sodium tablets are increased on an empty stomach. because levothyroxine sodium tablets may rapidly disintegrate. It is very important that the patient take the tablet with a full glass of water.

Adverse reactions

Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage. They include:

General: atigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating;

Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia;

Musculoskeletal: tremors, muscle weakness;

Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest;

Respiratory: dyspnea;

Gastrointestinal: diarrhea, vomiting, abdominal cramps and elevations in liver function tests;

Dermatologic: hair loss, flushing;

Endocrine: decreased bone mineral density;

Reproductive: menstrual irregularities, impaired fertility.

Overdosage

Symptoms of overdosage of levothyroxine may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.

Levothyroxine should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. Acute massive overdosage may be a life-threatening emergency, therefore, symptomatic and supportive therapy should be instituted immediately. If not contraindicated, the stomach should be emptied by emesis or gastric lavage to decrease the absorption of the agent. Activated charcoal or cholestyramine may also be used to decrease the absorption. Central and peripheral increased sympathetic activity may be treated by administering β-receptor antagonists, if not contraindicated.

Provide respiratory support as needed; control congestive heart failure and arrhythmia; control fever, hypoglycemia, and fluid loss as necessary. Large doses of antithyroid drugs (e.g., methimazole or propylthiouracil) followed in one or two hours by large doses of iodine may be given to inhibit synthesis and release of thyroid hormones.