Levothyroxine

BRAND NAMES

Common brand names of levothyroxine include:

• Synthroid (one of the most widely used brands) 
• Levoxyl 
• Euthyrox 
• Tirosint (capsule/gel form with fewer fillers) 
• Unithroid 
• Eltroxin (used in many countries outside the U.S.)

MECHANISM OF ACTION

Levothyroxine is a synthetic form of the thyroid hormone T4 that is converted in the body to the active hormone T3. T3 binds to nuclear receptors in cells and regulates gene expression, increasing metabolism and restoring normal thyroid function in hypothyroidism.

PHARMACOKINETICS

Absorption

Levothyroxine is absorbed mainly in the small intestine, especially the jejunum and ileum, after oral administration. Its absorption is variable (about 60–80%) and can be affected by food, calcium, iron, antacids, and certain medications, so it is usually recommended to take it on an empty stomach for consistent effect.

Distribution

Levothyroxine has a large volume of distribution, approximately 10–20 L/kg, reflecting extensive uptake into body tissues and strong binding to plasma proteins such as thyroxine-binding globulin (TBG), transthyretin, and albumin.

Metabolism

Levothyroxine is primarily metabolized in peripheral tissues such as the liver, kidneys, and muscles through deiodination, where it is converted into the active hormone triiodothyronine (T3) and inactive metabolites (reverse T3 and other iodothyronines). It also undergoes minor metabolism via conjugation in the liver, followed by biliary excretion and enterohepatic recycling.

Elimination

Levothyroxine is eliminated mainly through metabolism in the liver and kidneys, with its metabolites excreted in urine and bile. It has a long half-life of about 6–7 days, which supports once-daily dosing and stable hormone levels.

PHARMACODYNAMICS

Levothyroxine acts as a replacement for endogenous thyroxine (T4). After conversion to triiodothyronine (T3), it binds to nuclear thyroid hormone receptors and regulates gene transcription. This increases basal metabolic rate, oxygen consumption, and carbohydrate, fat, and protein metabolism, while also supporting normal growth, development, and cardiovascular function.

ADMINISTRATION

Levothyroxine is administered orally once daily, preferably on an empty stomach, about 30–60 minutes before breakfast to ensure consistent absorption. It is also available in intravenous form for emergency situations such as severe hypothyroidism or myxedema coma. Dosing is individualized based on age, weight, and thyroid-stimulating hormone (TSH) levels.

DOSAGE AND STRENGTH

Levothyroxine is available in multiple oral strengths to allow precise dose adjustment. Common tablet strengths range from 25 mcg to 300 mcg, including 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200, and 300 mcg. Initial dosing is individualized based on age, weight, and severity of hypothyroidism, with regular adjustment guided by thyroid-stimulating hormone (TSH) levels.

DRUG INTERACTIONS

Levothyroxine interacts with several drugs that can reduce its absorption or alter its effect. Calcium, iron, and antacids can decrease absorption, while drugs like rifampicin and phenytoin may increase its metabolism. Regular monitoring of TSH levels is needed when it is used with interacting medications.

FOOD INTERACTIONS

Levothyroxine absorption can be reduced by certain foods, especially those high in fiber, soy products, coffee, and calcium-fortified foods. For this reason, it is usually recommended to take it on an empty stomach with water and wait 30–60 minutes before eating to ensure consistent and effective absorption.

CONTRAINDICATIONS

Levothyroxine is contraindicated in patients with untreated thyrotoxicosis or uncorrected adrenal insufficiency, as it can worsen these conditions. It should also be used cautiously in individuals with acute myocardial infarction or significant cardiovascular disease, since it may increase cardiac workload and oxygen demand.

SIDE EFFECTS

• Palpitations

• Anxiety

• Insomnia

• Weight loss

• Heat intolerance

• Tremors

OVER DOSE

• Symptoms of hyperthyroidism (tachycardia, palpitations, anxiety) 

• Tremors and nervousness 

• Heat intolerance and sweating 

• Weight loss 

• Chest pain or arrhythmias (including atrial fibrillation) 

• Headache and insomnia

TOXICITY

Levothyroxine toxicity results from excessive thyroid hormone levels and causes symptoms like rapid heart rate, tremors, anxiety, heat intolerance, and weight loss. In severe cases, it may lead to arrhythmias and chest pain. Treatment involves dose reduction or discontinuation and supportive care.