Levothyroxine sodium

Thyroid hormones

ATC code: H03AA01 (Levothyroxine sodium)

Brand names

Synthroid, Levoxyl, Tirosint, Unithroid

Mechanism of action

Synthetic analogue of endogenous thyroxine (T4). Deiodinated in tissues to the biologically active triiodothyronine (T3), which binds nuclear thyroid hormone receptors and regulates genes controlling basal metabolism, growth, and development. Affects carbohydrate, lipid, and protein metabolism, the cardiovascular system, CNS, and skeleton.

Indications

Post-thyroidectomy state

First line

Lifelong replacement is required after total thyroidectomy. In thyroid cancer, TSH suppression to below 0.1 mU/L is the target in high-risk patients (per AJCC and staging) and 0.1–0.5 mU/L in intermediate risk. After subtotal resection for benign disease, the goal is euthyroidism with the same TSH target as for hypothyroidism.

Sources

Primary hypothyroidism

First line

Replacement therapy in primary hypothyroidism – first-line and sole therapy per 2014 and . Starting dose in young adults is 1.6 mcg/kg/day. In elderly and patients with ischemic heart disease, start at 12.5–25 mcg and titrate slowly. TSH target is 0.4–4.0 mU/L, with an upper limit up to 6 mU/L acceptable in the elderly. T4+T3 combinations are not routinely recommended.

Sources

Subclinical hypothyroidism

Individual decision

Subclinical hypothyroidism (TSH 4.5–10 mU/L, normal T4) may be treated selectively. recommends therapy when TSH exceeds 10 mU/L, in patients with TPO antibodies and hypothyroid symptoms, and in women who are pregnant or planning pregnancy. Asymptomatic elderly patients are generally not treated because of iatrogenic thyrotoxicosis risk.

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Weight loss in euthyroid patients

Not recommended

Using levothyroxine for weight loss in euthyroid patients is not supported by international guidelines and is potentially harmful. Iatrogenic thyrotoxicosis increases the risk of atrial fibrillation, osteoporosis, and cardiomyopathy without producing sustained weight loss.

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Practical notes

Timing and administration

Take in the morning on an empty stomach, 30–60 minutes before breakfast, with water only. During this window avoid coffee, tea, juice, milk, soy, and soy products. Alternative: bedtime dosing at least 3 hours after the last meal. Within 4 hours after the dose avoid: iron, calcium, magnesium, omega-3, proton pump inhibitors (pantoprazole, omeprazole), antacids, cholestyramine, and sevelamer — all impair absorption.

Monitoring

Check TSH 6–8 weeks after initiation or dose change. On stable therapy, recheck every 6–12 months. In pregnancy, check TSH every 4 weeks until mid-gestation, then every 6–8 weeks. When switching between brand-name and generic formulations, recheck TSH in 6–8 weeks (bioavailability may differ).

Pregnancy

Levothyroxine requirement increases 25–50 % from early pregnancy. In women with known hypothyroidism, the dose is increased immediately after pregnancy confirmation (2 additional tablets per week or 25–30 % daily dose increase). TSH target follows trimester- and population-specific reference ranges; when unavailable, 2017 sets the upper limit at 4.0 mU/L across all trimesters. The earlier strict target below 2.5 mU/L in the first trimester led to excessive dose escalation and has been revised.

Common myths

Myth: 'hormone medication is dangerous, better use herbs'. Fact: levothyroxine is bioidentical to endogenous thyroxine. Herbal products contain no active hormone and cannot compensate for hypothyroidism.

Myth: 'I can take a break from therapy'. Fact: replacement for primary hypothyroidism is lifelong. Discontinuation leads to symptom return within weeks and risks myxedema coma with prolonged decompensation.

Myth: 'levothyroxine helps with weight loss'. Fact: in euthyroid patients it does not produce sustained weight loss and is harmful (see the 'weight loss in euthyroid patients' indication).

Drug–nutrient interactions

Calcium

Calcium binds levothyroxine in the gut, reducing absorption by 20–25%. Take levothyroxine in the morning on an empty stomach; calcium 4 hours later or in the evening. Check TSH if dosing schedule changes.

Source: ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Iron

Iron binds levothyroxine in the gut. Absorption drops, TSH may rise. Separate by at least 4 hours: levothyroxine in the morning on empty stomach; iron 4 hours later or in the evening.

Source: ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Drug–drug interactions

6 pairs found. Sorted from critical to minor.

Major

Warfarin

Vitamin K antagonist anticoagulants

Mechanism

Thyroid hormones accelerate catabolism of vitamin K-dependent clotting factors. When levothyroxine starts or its dose increases, warfarin sensitivity rises and INR climbs within 1–4 weeks.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool. Severe cases include gastrointestinal or intracranial haemorrhage.

Management

When levothyroxine starts or is escalated, check INR at 1, 2, and 4 weeks and titrate warfarin (typically a 10–25% dose reduction). Once thyroid function stabilises, warfarin requirements stabilise too.

Sources

Pair details →

Moderate

Calcium carbonate

Mineral supplements. Calcium

Mechanism

Calcium binds levothyroxine in the gut as insoluble complexes, reducing absorption by 20–25%.

Symptoms

Return of hypothyroidism: fatigue, weight gain, cold intolerance, dry skin, low mood. In thyroid cancer, loss of TSH control.

Management

Take levothyroxine in the morning on empty stomach, 30–60 minutes before food and other drugs. Take calcium carbonate 4 hours after levothyroxine (e.g. at lunch or in the evening). Check TSH 6–8 weeks after starting calcium.

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Pair details →

Moderate

Omeprazole

Proton pump inhibitors

Mechanism

Proton pump inhibitors raise gastric pH, reducing levothyroxine absorption. TSH may rise 2–4 weeks after starting omeprazole.

Symptoms

Return of hypothyroidism: fatigue, weight gain, cold intolerance, dry skin, low mood. In thyroid cancer (TSH suppression needed), loss of control.

Management

Take levothyroxine 30–60 minutes before food and omeprazole. Check TSH 6–8 weeks after starting or stopping omeprazole. If TSH rises, increase levothyroxine by 12.5–25 mcg.

Sources

Pair details →

Minor

Amoxicillin

Penicillins with extended spectrum

Mechanism

Amoxicillin taken concurrently may slightly impair intestinal levothyroxine absorption. With separated dosing, the effect is clinically negligible.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Take levothyroxine in the morning on an empty stomach, 30–60 minutes before food and other medications. Take amoxicillin 4 hours later or at lunch. For short amoxicillin courses (5–10 days), no special TSH monitoring needed.

Sources

Pair details →

Minor

Ascorbic acid

Vitamins. Antioxidants

Mechanism

Ascorbic acid raises gastric acidity and improves levothyroxine absorption in patients with atrophic gastritis or hypochlorhydria. In healthy patients the effect is minimal.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

In patients with confirmed atrophic gastritis or PPI intolerance, ascorbic acid 500 mg with levothyroxine improves absorption. In healthy patients, no specific adjustment is needed. Monitor TSH on the usual schedule.

Sources

FDA: Synthroid (levothyroxine sodium) prescribing information (2017)

Pair details →

Minor

Atorvastatin

HMG-CoA reductase inhibitors (statins)

Mechanism

Hypothyroidism itself raises . Restoring euthyroid status on levothyroxine reduces statin need. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

On starting levothyroxine in patients on stable atorvastatin, check lipids 6–8 weeks after TSH normalises. If drops below target, atorvastatin can be reduced. In newly diagnosed hypothyroidism with hypercholesterolaemia, delay statin start until euthyroid status is achieved.

Sources

Pair details →

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Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMA

Spanish Medicines Information Centre (CIMA)

Label dated: 01/30/2025

FDA / DailyMed

FDA — DailyMed Drug Labels

Label dated: 05/19/2026

GRLS

Russian State Register of Medicines

Label dated: 04/23/2025

Safety

Contraindications

Untreated thyrotoxicosis
Acute myocarditis
Acute myocardial infarction
Untreated adrenal insufficiency
Hypersensitivity

Serious adverse effects

Iatrogenic thyrotoxicosis from chronic overdosing
Atrial fibrillation (on overdose, especially in elderly)
Decreased bone mineral density (on chronic suppressive doses)

Common adverse effects

Symptoms of overdose at excessive doses: tachycardia, tremor, weight loss, sweating, nervousness
Headache

PregnancyFDA A

FDA category A. Safe and required in pregnancy for hypothyroid women. Inadequate replacement is associated with miscarriage, preterm birth, and impaired cognitive development of the child.

Breastfeeding

Hale L1 · Compatible

Compatible with breastfeeding. The amount transferred to milk is physiologically insignificant.

Maternal half-life: 168 h
Maternal peak time: 2.5 h

Calculate RID Safe feeding window Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Levothyroxine sodium used for?

Levothyroxine sodium is evaluated for the following indications with varying evidence strength: Primary hypothyroidism (evidence tier A), Post-thyroidectomy state (evidence tier A), Subclinical hypothyroidism (evidence tier B). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Levothyroxine sodium?

Common side effects of Levothyroxine sodium (≥ 1 in 100): Symptoms of overdose at excessive doses: tachycardia, tremor, weight loss, sweating, nervousness, Headache. See the Safety section for uncommon and serious reactions.

Is Levothyroxine sodium safe during pregnancy?

FDA category A. FDA category A. Safe and required in pregnancy for hypothyroid women. Inadequate replacement is associated with miscarriage, preterm birth, and impaired cognitive development of the child.

Is Levothyroxine sodium compatible with breastfeeding?

Compatible with breastfeeding. The amount transferred to milk is physiologically insignificant.

Who should not take Levothyroxine sodium?

Levothyroxine sodium is contraindicated in: Untreated thyrotoxicosis; Acute myocarditis; Acute myocardial infarction; Untreated adrenal insufficiency; Hypersensitivity. Full list in the Safety section.

hormone medication is dangerous, better use herbs

levothyroxine is bioidentical to endogenous thyroxine. Herbal products contain no active hormone and cannot compensate for hypothyroidism.

I can take a break from therapy

replacement for primary hypothyroidism is lifelong. Discontinuation leads to symptom return within weeks and risks myxedema coma with prolonged decompensation.

levothyroxine helps with weight loss

in euthyroid patients it does not produce sustained weight loss and is harmful (see the 'weight loss in euthyroid patients' indication).

Mechanism of action

Indications

Post-thyroidectomy state

First line

Sources

Primary hypothyroidism

First line

Sources

Subclinical hypothyroidism

Individual decision

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Practical notes

Timing and administration

Monitoring

Pregnancy

Common myths

Drug–nutrient interactions

Calcium

Source: ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Iron

Iron binds levothyroxine in the gut. Absorption drops, TSH may rise. Separate by at least 4 hours: levothyroxine in the morning on empty stomach; iron 4 hours later or in the evening.

Source: ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Drug–drug interactions

6 pairs found. Sorted from critical to minor.

Major

Warfarin

Vitamin K antagonist anticoagulants

Mechanism

Thyroid hormones accelerate catabolism of vitamin K-dependent clotting factors. When levothyroxine starts or its dose increases, warfarin sensitivity rises and INR climbs within 1–4 weeks.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool. Severe cases include gastrointestinal or intracranial haemorrhage.

Management

Sources

Pair details →

Moderate

Calcium carbonate

Mineral supplements. Calcium

Mechanism

Calcium binds levothyroxine in the gut as insoluble complexes, reducing absorption by 20–25%.

Symptoms

Return of hypothyroidism: fatigue, weight gain, cold intolerance, dry skin, low mood. In thyroid cancer, loss of TSH control.

Management

Sources

ATA: Guidelines for the Treatment of Hypothyroidism (2014)

Pair details →

Moderate

Omeprazole

Proton pump inhibitors

Mechanism

Proton pump inhibitors raise gastric pH, reducing levothyroxine absorption. TSH may rise 2–4 weeks after starting omeprazole.

Symptoms

Return of hypothyroidism: fatigue, weight gain, cold intolerance, dry skin, low mood. In thyroid cancer (TSH suppression needed), loss of control.

Management

Take levothyroxine 30–60 minutes before food and omeprazole. Check TSH 6–8 weeks after starting or stopping omeprazole. If TSH rises, increase levothyroxine by 12.5–25 mcg.

Sources

Pair details →

Minor

Amoxicillin

Penicillins with extended spectrum

Mechanism

Amoxicillin taken concurrently may slightly impair intestinal levothyroxine absorption. With separated dosing, the effect is clinically negligible.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Sources

Pair details →

Minor

Ascorbic acid

Vitamins. Antioxidants

Mechanism

Ascorbic acid raises gastric acidity and improves levothyroxine absorption in patients with atrophic gastritis or hypochlorhydria. In healthy patients the effect is minimal.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Sources

FDA: Synthroid (levothyroxine sodium) prescribing information (2017)

Pair details →

Minor

Atorvastatin

HMG-CoA reductase inhibitors (statins)

Mechanism

Hypothyroidism itself raises . Restoring euthyroid status on levothyroxine reduces statin need. No direct pharmacokinetic interaction.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Sources

Pair details →

Safety

Contraindications

Untreated thyrotoxicosis
Acute myocarditis
Acute myocardial infarction
Untreated adrenal insufficiency
Hypersensitivity

Serious adverse effects

Iatrogenic thyrotoxicosis from chronic overdosing
Atrial fibrillation (on overdose, especially in elderly)
Decreased bone mineral density (on chronic suppressive doses)

Common adverse effects

Symptoms of overdose at excessive doses: tachycardia, tremor, weight loss, sweating, nervousness
Headache

PregnancyFDA A

FDA category A. Safe and required in pregnancy for hypothyroid women. Inadequate replacement is associated with miscarriage, preterm birth, and impaired cognitive development of the child.

Breastfeeding

Hale L1 · Compatible

Compatible with breastfeeding. The amount transferred to milk is physiologically insignificant.

Maternal half-life: 168 h
Maternal peak time: 2.5 h

Calculate RID Safe feeding window Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Frequently asked

What is Levothyroxine sodium used for?

What are the side effects of Levothyroxine sodium?

Is Levothyroxine sodium safe during pregnancy?

Is Levothyroxine sodium compatible with breastfeeding?

Compatible with breastfeeding. The amount transferred to milk is physiologically insignificant.

Who should not take Levothyroxine sodium?

hormone medication is dangerous, better use herbs

levothyroxine is bioidentical to endogenous thyroxine. Herbal products contain no active hormone and cannot compensate for hypothyroidism.

I can take a break from therapy

replacement for primary hypothyroidism is lifelong. Discontinuation leads to symptom return within weeks and risks myxedema coma with prolonged decompensation.

levothyroxine helps with weight loss

in euthyroid patients it does not produce sustained weight loss and is harmful (see the 'weight loss in euthyroid patients' indication).