What Is Levothyroxine?

In 1891, Dr. George R. Murray first demonstrated that hypothyroid patients benefited from injections of sheep thyroid. No one knew what the active ingredient in thyroid extract was until 1915, when Nobel laureate E. C. Kendall identified "thyroxin." In 1926, Sir Charles Harington identified the correct chemical structure of the active ingredient of thyroid extract and renamed it "thyroxine."

Until the 1950s, thyroxine preparations were not as effective as desiccated (dried and powdered) animal thyroid glands because they were not well absorbed and because they were also difficult to produce in large quantities. Therefore, from the late 1890s until the 1950s, desiccated animal thyroid was the primary source of thyroid hormone replacement. In 1958, the first well-absorbed synthetic (man-made) thyroxine tablets, formulated as sodium levothyroxine, became commercially available in the United States. Today, the preferred preparation for thyroid hormone treatment is brand-name synthetic sodium levothy­roxine, also called levothyroxine, L-thyroxine, or T4.

Levothyroxine therapy is indicated for all patients with hypo­thyroidism. The most common cause of hypothyroidism in the United States is Hashimoto's thyroiditis. In addition, nearly a million people have taken radioactive iodine to treat their hyperthyroidism, and, consequently, most of them have become hypothyroid.

Under certain circumstances, levothyroxine may also be indicated for patients with the following thyroid problems:

• goiter
• solitary thyroid nodule
• multinodular goiter
• thyroid cancer
• thyroiditis
• hyperthyroidism treated with antithyroid drugs

There are some differences in the manufacturing, composition (fillers and dyes), and absorption among these preparations. For this reason, it is preferable for patients to take the same brand-name levothyroxine consistently. If a change is made from one brand-name levothyroxine to another, thyroid function test results should be checked six or more weeks later to confirm that the patients are still getting the right amount of levothyroxine.

Levothyroxine tablets are color-coded, although different manu­facturers utilize different color schemes. All the brand-name pills are round, except for Levoxyl, which is shaped somewhat like a thyroid gland. One way patients can confirm that their prescriptions have been filled correctly is by checking the color of dispensed pills; errors do occur.

Physicians can prescribe either brand-name or generic levothyroxine. If physicians want their patients to take a specific brand of levothyroxine, they will either write a prescription or call a pharmacist with verbal orders to dispense the prescribed brand. Therefore, if the words "Levoxyl," "Synthroid," "Unithroid," or "Levothroid" do not appear on the prescription label, then it is likely that patients are getting generic levothyroxine preparations. Furthermore, if only the words "sodium levothyroxine" or "levothyroxine" are on the label, then it is also likely that patients are getting generic rather than brand-name preparations.

Each state decides whether, and under what circumstances, phar­macists may substitute generic levothyroxine for a brand-name product without informing prescribing physicians. Furthermore, some physicians' contracts with health care providers permit the health care providers to substitute generic medications for brand-name products without informing prescribing physicians. Therefore, patients should be aware that they might not get exactly what their doctors ordered, and that their doctors might not be aware of the change either.

There are several reasons many physicians recommend brand-name over generic preparations of levothyroxine, including:

• quality control
• stability of manufacturer
• variety of available dosages

In the past, there has been less quality control in the production of generic levothyroxine than in brand-name levothyroxine. New FDA regulations may eliminate this discrepancy, although manufacturers of generic levothyroxine are "generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness."

Even if manufacturers of generic levothyroxine are now meeting the same production standards as the manufacturers of Synthroid, Unithroid, Levothroid, and Levoxyl, there are other reasons to prefer name brands. Generic manufacturers have no name recognition and may come and go in the marketplace more often than long-standing manufacturers of brand-name levothyroxine. For this reason, pharma­cists may no longer be able to get generic levothyroxine from the same manufacturer. Furthermore, when substitution of generic for brand-name levothyroxine is permitted, pharmacists may select generic levothyroxine from any manufacturer-and it doesn't have to be the same manufacturer each time they refill the prescription. Therefore, when generic levothy­roxine is prescribed, patients unknowingly may take preparations whose properties are not the same as their previously dispensed levothyroxine.

Another important factor to consider is that each brand-name manufacturer of levothyroxine offers eleven to twelve strengths from which physicians may choose. On average, a patient's levothyroxine dosage is changed once every three years. A change in dosage occurs even more often when levothyroxine treatment is initiated or when a hypothyroid patient becomes pregnant. Therefore, it is important that the prescribed drug is available in as many strengths as possible. Since many generic manufacturers offer a limited range of dosages, there is a higher likelihood of being switched from one manufacturer to another when generic drugs are prescribed.