Levothyroxine !

Synthetic thyroid hormone (T4) taken daily to replace what an underactive thyroid no longer makes. Adjusted with blood TSH.

Updated 2026-11-01

Class: Thyroid hormones
Receptor: Thyroid hormone receptor β (and α)
ATC code: H03AA01
WHO Model List of Essential Medicines

Also called: L-thyroxine, T4

Thyroid hormone receptor β (and α)Levothyroxine

The figure shows thyroxine (T4, levothyroxine itself) bound to the ligand-binding domain of human thyroid hormone receptor β; in the body most of the effect comes from T3 made from it.

Target in 3D: Thyroid hormone receptor β (and α). PDB structure 1Y0X (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Levothyroxine is identical to natural thyroxine (T4). In tissues, deiodinases remove one iodine and turn it into T3, which binds nuclear thyroid hormone receptors and changes transcription of genes that set metabolic rate, heat production, heart rate, growth and brain development. Because T4 has a long half-life and is converted steadily, once-daily dosing gives stable levels.

Levothyroxine (T4) circulates bound to plasma proteins
Deiodinases in tissues turn T4 into active T3
T3 binds nuclear thyroid hormone receptors
Gene transcription changes: metabolism and heart rate rise

Pharmacokinetics

Absorption: Absorbed in the small intestine; food, calcium, iron and some drugs reduce absorption
Distribution: Almost entirely bound to plasma proteins
Metabolism: Deiodinated in tissues to T3 (active) and reverse T3 (inactive)
Half-life: Long, longer than T3, so changes in dose take weeks to show in TSH

Indications

Primary, secondary or tertiary hypothyroidism, congenital or acquired Hypothyroidism →
TSH suppression after surgery and radioactive iodine for differentiated thyroid cancer Thyroid cancer (papillary) →

Adverse effects

Common

Symptoms of excess hormone: palpitations, tremor, insomnia, heat intolerance, weight loss
Diarrhoea
Partial hair loss in the first months
Menstrual changes

Contraindications

Uncorrected adrenal insufficiency
Treatment of obesity or weight loss (boxed warning)

Key interactions

Calcium carbonate, iron salts, phosphate binders (sevelamer, lanthanum): Bind levothyroxine and reduce its absorption; doses are separated by several hours
Bile acid sequestrants (cholestyramine, colesevelam) and ion-exchange resins: Lower absorption; levothyroxine is given hours before them
Proton pump inhibitors and antacids: May lower absorption
Warfarin: Stronger anticoagulant effect as thyroid function normalises
Insulin and oral antidiabetic drugs: Glucose control may worsen; requirements may rise
Digoxin: Digoxin levels and effect may fall

What is monitored

TSH (free T4 in central hypothyroidism)
Heart rate and symptoms of excess hormone
Thyroid tests early in pregnancy and through it
Growth and development in children

Administration and safety

Given once daily on an empty stomach, before breakfast with water
Separated by several hours from calcium, iron, antacids and binding resins
Narrow therapeutic index: switching products can change levels, so TSH is rechecked
Biotin supplements can distort thyroid test results

Nursing care

Teach a fixed daily routine: same time, empty stomach, with water
Check heart rate; report palpitations, chest pain or tremor
Explain that it is usually lifelong and that improvement takes weeks
Ask women to report pregnancy early: needs usually rise
Review other drugs and supplements taken at the same time of day

Pregnancy and breastfeeding

Essential in pregnancy when hypothyroidism exists: needs usually rise, so thyroid tests are checked often; untreated hypothyroidism harms the baby.

Test yourself

Think of the answer, then tap the question to see it.

Why is levothyroxine given on an empty stomach and apart from calcium or iron?

Food, calcium and iron bind it or reduce its absorption, making levels lower and less predictable.

Why are TSH levels rechecked only weeks after a levothyroxine dose change?

T4 has a long half-life, so a new steady state and the TSH response take weeks to settle.

An older patient with coronary disease starts levothyroxine. What is the main risk?

Angina, arrhythmia or infarction from the rise in heart rate and oxygen demand; treatment starts low and rises slowly.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Levothyroxine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2019); DailyMed - LEVOTHYROXINE SODIUM tablet (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Farmacología básica y clínica (Katzung), 16.ª ed., cap. 38 (McGraw Hill, 2025).

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Representative model, for educational purposes only.