Levothyroxine

Levothyroxine sodium (LT4) is a synthetic form of thyroxine (T4), the primary hormone produced by the thyroid gland. T4 is itself a relatively inactive prohormone; it is converted in peripheral tissues — primarily the liver, kidneys, and muscles — to triiodothyronine (T3), the biologically active form that binds thyroid hormone receptors in virtually every cell in the body and regulates metabolism, heart rate, growth, body temperature, and numerous other physiological processes.¹

Levothyroxine has an elimination half-life of approximately 6–7 days, enabling once-daily dosing and gradual, stable blood levels when dosed consistently. It is one of the most commonly prescribed medications in the United States and is the first-line, evidence-based standard of care for treatment of hypothyroidism of any cause. It is available in multiple branded and generic formulations including tablets (many strengths), capsules (Tirosint), and liquid solution; formulations differ slightly in bioavailability, and switching between formulations may require TSH reassessment.¹

Levothyroxine is FDA-approved as replacement or supplemental therapy for:¹

• Hypothyroidism: Primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis.
• Subclinical hypothyroidism.
• Pituitary TSH suppression: In the management or prevention of thyroid goiters and as adjunctive therapy for thyroid cancer.

Off-label uses: Levothyroxine is sometimes used off-label in euthyroid patients for weight management — the FDA label explicitly warns against this, noting that doses within or near the physiological range are ineffective for weight reduction in euthyroid individuals, and that supraphysiological doses can produce serious or life-threatening toxicity, particularly when combined with sympathomimetic agents.¹

Levothyroxine dosing is highly individualized, weight-based as a starting estimate, and titrated based on TSH monitoring.¹

• General adult replacement: Typical full replacement dose is approximately 1.6 mcg/kg/day, though older patients and those with cardiac disease typically start at lower doses (25–50 mcg/day) with gradual titration.
• Elderly or cardiac patients: Starting doses of 12.5–25 mcg/day with slow upward titration are common to avoid precipitating angina or arrhythmia.
• Pregnancy: Requirements typically increase 20–30% during the first trimester; thyroid function should be monitored closely throughout pregnancy.

TSH is the primary laboratory marker used to assess adequacy of replacement; a TSH within the normal range for the laboratory is the conventional therapeutic target, though the optimal target TSH may differ by individual circumstances (age, symptoms, pregnancy status, presence of thyroid cancer).

Real-world practice: Consistency of timing and conditions matters more than the specific time chosen. Taking levothyroxine at the same time each day under the same conditions (fasting vs. with food, with or without coffee) produces more stable TSH levels than varying the timing or conditions. Some patients find better tolerability taking it at bedtime rather than in the morning, which also avoids the interaction window with breakfast, coffee, and morning supplements.

Oral. Levothyroxine tablets or capsules must be taken on an empty stomach, 30–60 minutes before the first meal of the day (or at least 3–4 hours after the last meal), to maximize consistent absorption. Intravenous formulations are available for clinical settings (e.g., myxedema coma) where oral administration is not feasible.

Store at controlled room temperature, 59°F to 77°F (15°C to 25°C), away from light and moisture. Protect from heat and humidity. Do not store in the bathroom.¹

Levothyroxine has a narrow therapeutic index — small changes in dose or absorption can produce clinically significant effects. Several factors affect absorption and stability:¹

• Food and timing: Consistent timing of administration is critical. Taking levothyroxine with food — especially high-fiber foods, calcium-fortified foods, or coffee — substantially reduces absorption.
• Calcium and iron supplements: Calcium carbonate, calcium citrate, and iron supplements all significantly impair levothyroxine absorption; these should be taken at least 4 hours apart from levothyroxine.
• Medications affecting absorption or metabolism: Cholestyramine, colestipol, sucralfate, antacids, proton pump inhibitors, and many other agents affect levothyroxine absorption or metabolism. Thyroid hormone requirements may also change with initiation or discontinuation of estrogens, androgens, or other medications that alter thyroid binding globulin.
• Signs of overreplacement (hyperthyroidism): Palpitations, tachycardia, heat intolerance, sweating, weight loss, tremor, irritability, insomnia, and decreased bone density with chronic excess. These are also the adverse effects that occur with supraphysiological doses used inappropriately for weight loss.
• Signs of underreplacement (hypothyroidism): Fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss, cognitive slowing, bradycardia, and depression.
• Formulation consistency: Different brands and generics of levothyroxine are not necessarily interchangeable without TSH reassessment. Patients on levothyroxine should inform their pharmacist if a formulation substitution occurs, and TSH should be rechecked 4–6 weeks after any change.