Levothyroxin (L‑T4)
Synthetic thyroxine (T4) hormone replacement for hypothyroidism. WHO Essential Medicines, one of the most prescribed drugs globally. ATA and ETA endocrine guideline anchor.
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WHAT IS LEVOTHYROXIN (L-T4)?
Detailed overview
Levothyroxine (L-T4) is the synthetic levo-isomer of endogenous thyroxine, developed by Knoll AG in the 1950s, with Synthroid receiving FDA approval in 1958. T4 is a prohormone, converted peripherally to active T3 triiodothyronine by deiodinase enzymes (D1, D2, D3). Weekly steady-state plasma level is reached over 4-6 weeks due to the 6-7-day half-life. The ATA 2014 hypothyroidism guideline (Jonklaas 2014 PMID 25266247) places levothyroxine monotherapy as standard treatment in primary (Hashimoto) and secondary hypothyroidism; T3 supplementation is not routinely indicated except in carefully documented symptomatic or T3-conversion-impaired cases. Body-weight-based starting dose ~1.6 µg/kg/day; in age >65 or ischemic heart disease, more cautious start (25-50 µg/day) recommended.
ATC code
H03AA01
Prescription
Prescription only (Rx)
Mechanism
T4 hormone replacement (converts to T3 peripherally)
Half-life
6-7 days (once-daily dosing)
Onset
4-6 weeks (steady-state TSH reduction)
Data console
Lab data
Safety
Side effects, stop signs, contraindications
Side effects · 7
- Overdose (iatrogenic thyrotoxicosis) symptoms: palpitations, tachycardia, tremor, sweating, heat intolerance, anxiety, insomnia, weight loss – the most common and clinically important effect, signalling too high or too fast a dose.
- Cardiac arrhythmia, especially atrial fibrillation – markedly increased risk in elderly patients and with chronic subclinical over-replacement (TSH < 0.1 mIU/L); angina or ischaemia may be provoked in pre-existing heart disease.
- Reduced bone mineral density, osteoporosis and increased fracture risk with chronic over-replacement – particularly in postmenopausal women and on long-term TSH-suppressive therapy.
- Under-replacement (persistent hypothyroidism) symptoms: fatigue, cold intolerance, constipation, depression, hair loss, oedema, weight gain – not an adverse drug effect in the strict sense but a sign of inadequate dose titration.
- Headache, diarrhoea, appetite change and menstrual irregularities – mainly during the titration phase or with rapid dose increases.
- In children, transient hair loss in the first months and rarely pseudotumour cerebri (benign intracranial hypertension); rapid over-correction may accelerate bone maturation.
- Rare hypersensitivity reactions to excipients (e.g. lactose, dyes): rash, urticaria, pruritus, angioedema; anaphylaxis very rare – a lactose-free formulation (Tirosint) may help.
Contraindications · 4
- Untreated thyrotoxicosis (hyperthyroidism)
- Untreated adrenal insufficiency (Addison) – corticosteroid replacement mandatory before levothyroxine
- Acute MI or active ischemia (consider; cautious initiation)
- Known hypersensitivity to active substance or excipients
Related Pharmaceuticals
Same therapeutic category
Studies
Related research and clinical findings
Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force
Jonklaas J, Bianco AC, Bauer AJ et al.
Consensus statement #1: subclinical thyroid disease
Surks MI, Ortiz E, Daniels GH et al.
Levothyroxine timing: morning vs bedtime (RCT)
Bolk N, Visser TJ, Nijman J et al.
2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy
Alexander EK, Pearce EN, Brent GA et al.
Combination treatment with T4 and T3 vs T4 alone in hypothyroidism: meta-analysis
Grozinsky-Glasberg S, Fraser A, Nahshoni E et al.
Levothyroxine dose requirements and TSH in pregnancy
Alexander EK, Marqusee E, Lawrence J et al.
2014 ETA Guidelines: the use of L-T4 + L-T3 in the treatment of hypothyroidism
Wiersinga WM, Duntas L, Fadeyev V et al.
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Have a question about Levothyroxin (L‑T4)?
Educational drug info from official sources (PubMed, FDA, EMA). Does NOT replace medical consultation or the SmPC. Talk to your doctor!
The information here is for educational and scientific purposes only. Medication use requires medical consultation and a prescription. The indications, dose ranges, and side effects listed here do NOT replace the official Summary of Product Characteristics (SmPC) or consultation with a physician. Do not start or stop any medication on your own. In an emergency, call your local emergency number.