LEVOTHYROXINE SODIUM
Clinical safety rating: safe
Many drugs can decrease absorption (eg calcium iron) Can cause cardiac ischemia and arrhythmias in overdose.
Synthetic T4 hormone that is deiodinated to T3, which binds to thyroid hormone receptors in the nucleus, regulating gene transcription and increasing metabolic rate.
| Metabolism | Primarily hepatic deiodination (type 1 and 2 deiodinases) to T3 and reverse T3; also conjugation (glucuronidation, sulfation) and excretion in bile and urine. |
| Excretion | Renal (approximately 50% as unchanged drug and conjugates); fecal (biliary excretion of conjugates, ~20-30%); minor pulmonary and dermal routes. |
| Half-life | 6-7 days (euthyroid); prolonged in hypothyroidism (9-10 days) and shortened in hyperthyroidism (3-4 days). |
| Protein binding | 99.5% bound primarily to thyroxine-binding globulin (TBG), also to transthyretin (TTR) and albumin. |
| Volume of Distribution | 0.2-0.3 L/kg (central); total Vd ~8-10 L (reflects extensive tissue distribution including muscle, liver, kidney). |
| Bioavailability | Oral: 50-80% (absorption affected by food, fiber, and other drugs). Intravenous: 100%. |
| Onset of Action | Oral: 3-5 days for detectable serum levels; 10-12 days for full clinical effect (metabolic effects). Intravenous: 24-48 hours for clinical effect. |
| Duration of Action | Oral: Approximately 2-3 weeks after discontinuation due to long half-life; clinical effects persist for 10-14 days after single dose. |
Initial adult dose: 25-50 mcg orally once daily, titrated by 12.5-25 mcg every 6-8 weeks based on TSH. Usual maintenance: 1.6 mcg/kg/day. Route: oral; IV dose is 50% of oral dose.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for renal impairment; however, monitor TSH levels closely as levothyroxine metabolism unaffected by renal function. Patients on dialysis may require reduced dose due to loss of thyroid binding proteins. |
| Liver impairment | No specific Child-Pugh based guidelines. In severe hepatic impairment (Child-Pugh C), consider starting at lower doses (e.g., 12.5-25 mcg/day) due to reduced T4 to T3 conversion and increased risk of cardiac side effects; titrate slowly. |
| Pediatric use | Initial dose: 10-15 mcg/kg/day orally (infants: higher end, older children: lower end). Typical ranges: 0-6 months: 25-50 mcg/day; 6-12 months: 50-75 mcg/day; 1-5 years: 75-100 mcg/day; 6-12 years: 100-125 mcg/day; >12 years: 100-200 mcg/day or 2-3 mcg/kg/day. Titrate based on TSH and free T4. |
| Geriatric use | Start at lower doses (e.g., 12.5-25 mcg/day orally) due to increased sensitivity and higher risk of cardiovascular adverse effects. Increase by 12.5 mcg every 4-6 weeks. Monitor cardiac status closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Many drugs can decrease absorption (eg calcium iron) Can cause cardiac ischemia and arrhythmias in overdose.
| FDA category | Human |
| Breastfeeding | Excreted into breast milk in low amounts; not expected to cause adverse effects in infant at maternal therapeutic doses. M/P ratio not well defined but clinically negligible. Compatible with breastfeeding; monitor infant thyroid function if high maternal doses used. |
| Teratogenic Risk | No known significant teratogenic risk. Endogenous thyroid hormone is essential for fetal neurodevelopment; untreated maternal hypothyroidism is associated with adverse outcomes (e.g., lower IQ, preterm birth). Levothyroxine crosses placenta minimally. First trimester: No evidence of malformations. Second/third trimester: High doses may cause fetal tachycardia or transient neonatal hyperthyroidism. |
■ FDA Black Box Warning
Not recommended for weight loss or treatment of obesity; high doses can cause serious or life-threatening toxicity.
| Common Effects | Palpitations |
| Serious Effects |
Untreated adrenal insufficiency, untreated thyrotoxicosis, acute myocardial infarction, hypersensitivity to levothyroxine or any excipients.
| Precautions | Cardiovascular disease (angina, arrhythmias, hypertension), adrenal insufficiency (risk of adrenal crisis), diabetes mellitus (may increase blood glucose), concomitant use with anticoagulants (enhanced effect), osteoporosis with long-term TSH suppression in postmenopausal women. |
| Food/Dietary | Fiber supplements, high-fiber foods (e.g., bran), soy products, walnuts, and grapefruit juice may reduce absorption. Cottonseed meal and infant soy formula can bind levothyroxine. Avoid concurrent intake; maintain consistent dietary habits and take medication with water only. |
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| Fetal Monitoring | Monitor maternal TSH and free T4 every 4-6 weeks during pregnancy; adjust dose to maintain TSH in trimester-specific ranges. Fetal ultrasound for growth and goiter in cases of overtreatment or undertreatment. Postpartum: Recheck TSH 4-6 weeks; often need dose reduction. |
| Fertility Effects | Untreated hypothyroidism can cause anovulation, menstrual irregularities, and impaired fertility. Levothyroxine replacement restores euthyroid state, improving fertility. No direct adverse effect on fertility. |
| Clinical Pearls | Levothyroxine absorption is reduced by calcium carbonate, iron, aluminum-containing antacids, bile acid sequestrants, and sucralfate; separate administration by at least 4 hours. Do not switch brands without retesting TSH because of bioavailability differences. In hypothyroid patients with cardiac disease, start at 12.5-25 mcg daily and titrate slowly to avoid exacerbation of angina or arrhythmias. TSH suppression therapy for thyroid cancer requires higher doses. Monitor TSH 6-8 weeks after dose changes. Pregnancy increases requirements by 20-30%; check TSH immediately upon confirmation of pregnancy and adjust dose. |
| Patient Advice | Take on an empty stomach at least 30-60 minutes before breakfast with a full glass of water. · Do not stop taking without consulting prescriber; replacement therapy is usually lifelong. · Separate from calcium supplements, iron, antacids, and high-fiber foods by at least 4 hours. · Do not change brands without prescriber approval. · Notify prescriber if pregnant, plan pregnancy, or breastfeeding as dose adjustments are needed. · Report symptoms of over- or under-treatment: palpitations, anxiety, insomnia (hyperthyroidism); fatigue, weight gain, cold intolerance (hypothyroidism). · Keep regular appointments for blood tests (TSH) to monitor therapy. |