What Is Levothyroxine (Synthroid, Levoxyl)? Uses, Side Effects & Warnings

Levothyroxine sodium is a synthetic form of thyroxine (T4), the primary hormone produced by the thyroid gland. It is sold under multiple brand names including Synthroid, Levoxyl, Tirosint, and Unithroid, in addition to generic formulations. Levothyroxine tablets come in a notably wide range of strengths — from 25 mcg up to 300 mcg — because precise dosing is critical in thyroid hormone replacement. It consistently ranks as the most prescribed medication in the United States, with tens of millions of prescriptions written annually, reflecting the high prevalence of hypothyroidism — particularly in women and older adults.

What Levothyroxine Is Used For

Levothyroxine is primarily used to treat hypothyroidism — a condition in which the thyroid gland does not produce enough thyroid hormone. The most common cause in the United States is Hashimoto's thyroiditis, an autoimmune condition in which the immune system attacks the thyroid. Other causes include prior thyroid surgery, radioactive iodine treatment for hyperthyroidism or thyroid cancer, and certain medications (including amiodarone and lithium). Hypothyroidism causes a wide range of symptoms: fatigue, weight gain, feeling cold, dry skin, hair loss, constipation, depression, and slow heart rate.

Levothyroxine is also used for thyroid-stimulating hormone (TSH) suppression — specifically in the treatment of thyroid cancer (post-thyroidectomy) and some cases of thyroid nodules, where maintaining very low TSH levels helps prevent cancer recurrence or nodule growth. It is sometimes used off-label for euthyroid goiter (enlarged thyroid in people with normal thyroid function).

How Levothyroxine Works

The thyroid gland produces two active hormones: thyroxine (T4, roughly 80% of thyroid secretion) and triiodothyronine (T3, the more potent, faster-acting form). T4 is largely a prohormone — much of it is converted to the active T3 in peripheral tissues (liver, kidney, muscle) by enzymes called deiodinases.

Levothyroxine is identical in structure to the body's own T4. Once absorbed, it enters cells and is converted to T3. T3 then binds to thyroid hormone receptors in cell nuclei, influencing the expression of genes that regulate metabolism, heart rate, body temperature, growth, and neurological function. By replenishing T4 levels, levothyroxine normalizes the entire cascade of thyroid hormone action throughout the body.

Common Side Effects

When levothyroxine is properly dosed to bring thyroid levels into the normal range, it should produce minimal or no side effects — the goal is to replicate normal thyroid function. Side effects typically reflect either too much or too little thyroid hormone:

• Signs of too much (overtreatment/hyperthyroid symptoms): palpitations, rapid heart rate, heat intolerance, sweating, nervousness, insomnia, tremor, weight loss, diarrhea
• Signs of too little (undertreatment/hypothyroid symptoms): persistent fatigue, weight gain, feeling cold, constipation, dry skin, depression
• Long-term overtreatment increases the risk of atrial fibrillation (especially in older adults) and bone density loss (osteoporosis)

Important Warnings

Key Drug Interactions

Levothyroxine has extensive and clinically critical absorption interactions. Several common substances significantly reduce how much levothyroxine is absorbed from the gut:

• Calcium carbonate and calcium-fortified foods — including calcium supplements, antacids containing calcium, and calcium-fortified orange juice. These should be separated from levothyroxine by at least 4 hours.
• Iron supplements and multivitamins with iron — must be taken at least 4 hours apart from levothyroxine.
• Proton pump inhibitors (omeprazole, pantoprazole) — reduce stomach acid needed for optimal T4 absorption. The liquid gel-cap formulation (Tirosint) is less affected.
• Cholestyramine and colestipol (bile acid sequestrants) — separate by 4–5 hours.
• Soybean products — high-soy diets can impair T4 absorption.
• Walnuts, dietary fiber, and coffee — can also reduce absorption if consumed simultaneously.

Several medications affect thyroid hormone metabolism. Rifampin, carbamazepine, and phenytoin increase the clearance of thyroid hormone, potentially requiring higher levothyroxine amounts. Amiodarone, which contains large amounts of iodine, can cause either hypothyroidism or hyperthyroidism and interferes with T4 to T3 conversion. Estrogen (including oral contraceptives and hormone replacement therapy) increases thyroid-binding globulin, potentially requiring increased levothyroxine amounts. Pregnancy similarly increases thyroid hormone requirements, typically requiring monitoring and dose adjustment within the first trimester.

Frequently Asked Questions

Why must levothyroxine be taken on an empty stomach?

Levothyroxine absorption is highly sensitive to the contents of the stomach and gastrointestinal tract. Food — particularly calcium-rich foods, fiber, coffee, and high-fat foods — can bind to levothyroxine in the gut and reduce absorption by as much as 40%. The standard recommendation is to take levothyroxine first thing in the morning, at least 30–60 minutes before breakfast and other medications. Patients who have difficulty maintaining this routine may alternatively take levothyroxine at bedtime (at least 3–4 hours after the last meal), which some studies suggest may achieve slightly better absorption.

Is Synthroid the same as generic levothyroxine?

The FDA considers generic levothyroxine bioequivalent to Synthroid — meaning they should have the same pharmacological effect. However, thyroid hormone therapy is uniquely sensitive to even small differences in absorption, and some patients (and endocrinologists) report that switching between brands or between brand and generic can shift TSH levels enough to cause symptoms. For this reason, many thyroid specialists recommend that patients remain on the same brand or manufacturer consistently, and have their TSH rechecked after any formulation change.

What happens if I miss a dose?

Because levothyroxine has a long half-life (about 7 days), missing a single dose does not cause immediate symptoms. If a dose is missed, it can generally be taken as soon as remembered — even if it means taking two doses close together (the next day, for example). This is one of the few medications where taking two doses on the same day is acceptable and is recommended in most prescribing information when a dose is forgotten.

Can I take levothyroxine during pregnancy?

Not only can levothyroxine be taken during pregnancy — it is essential for pregnant women with hypothyroidism. Untreated or undertreated hypothyroidism during pregnancy is associated with miscarriage, pre-eclampsia, preterm delivery, and impaired fetal neurological development. Thyroid hormone requirements increase substantially during pregnancy, usually starting in the first trimester. Thyroid function should be tested promptly after pregnancy is confirmed and monitored regularly throughout gestation.