Levothyroxine
Levothyroxine
Generic Name
Levothyroxine
Mechanism
- Levitates the thyroid hormone cycle by providing exogenous T4 (thyroxine).
- Inside peripheral tissues, T4 is deiodinated to the more active T3 (triiodothyronine) via 5’-deiodinase enzymes.
- Once T3 binds to nuclear thyroid hormone receptors (TRα/β), it modulates transcription of target genes, increasing basal metabolic rate, cardiac output, and oxygen consumption.
- Restoring physiologic T4/T3 levels corrects the hypothyroid state and normalizes the hypothalamic‑pituitary‑thyroid axis, thereby suppressing TSH release.
Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | 70–80 % orally | Maximized with a 30–60 min fast; food, calcium, iron, PPIs, soy, and high‑fiber products inhibit uptake. |
| Bioavailability | 70–80 % | Variable; consistent timing of administration improves reliability. |
| Distribution | T4: 80–90 % protein‑bound (mostly to thyroxine‑binding globulin); T3: 65–70 % protein‑bound | Only the free fraction is biologically active. |
| Half‑life | T4: ~6–7 days in hypothyroid patients; T3: ~1 day | Long half‑life permits once‑daily dosing. |
| Metabolism | Hepatic deiodination to T3 and reverse T3; renal excretion of metabolites | No significant drug–drug interactions via CYP enzymes. |
| Volume of distribution | ~0.5 L/kg | Reflects extensive tissue binding. |
Indications
- Primary hypothyroidism (Hashimoto's thyroiditis, post‑thyroidectomy, radiation thyroiditis).
- Secondary or tertiary hypothyroidism in congenital absent/defective TSH production.
- Thyroid hormone replacement for thyroid hormone‑deficient states (e.g., in post‑thyroidectomy patients).
- Adjuvant therapy in thyroid cancer for TSH suppression.
- Congenital hypothyroidism when neonatal screening identifies deficiency.
- Pre‑operative preparation prior to certain surgeries (e.g., in patients with a history of autoimmune thyroid disease).
Contraindications
| Category | Key Points |
| Contraindications |
• Acute myocardial ischemia (increased adrenergic demand). • Uncontrolled hypertension. • Uncorrected heart disease (e.g., uncontrolled arrhythmias). |
| Warnings |
• Thyroid storm precipitated by abrupt cessation or excessive dosing. • Pregnancy: use the lowest effective dose; no definitive risk, but monitoring TSH is essential. • Pediatric: dose adjusted for body weight; careful monitoring to avoid hyperthyroidism. |
| Precautions |
• Liver disease: may alter deiodination rates. • Renal impairment: monitor for accumulation of metabolites. |
Dosing
- Adults
- *Initial* (non‑pregnant): 1.6 µg/kg/day → ~100–125 µg daily.
- *Maintenance*: 50–150 µg/day, titrated to symptoms and TSH.
- *Pregnancy*: increase by 30–50 µg each trimester if TSH >2.5 mIU/L.
- Children
- 10–15 µg/kg/day in the first 12 months; <10 µg/kg/day thereafter.
- Elderly
- Start lower (25–50 µg) to avoid cardiac side‑effects; titrate slowly.
- Administration
- Take exactly 30–60 min before breakfast.
- Avoid concomitant calcium, iron, sucralfate, PPIs, or soy within 4 h of dosing.
- If delayed, take with a small meal; reschedule next dose 12 h later.
Formulation
• Liquid solutions for pediatric/elderly or special GI absorption needs—ensure proper refrigeration and use by expiration.
• Tablets: 25–200 µg; avoid crushing (may degrade potency).
Adverse Effects
- Common
- Headache, insomnia, increased appetite.
- Mild tachycardia, palpitations, anxiety.
- Diarrhea or constipation (dose‑dependent).
- Serious
- Cardiovascular: arrhythmias, angina, myocardial infarction.
- Thyroid storm if dose exceeded or abruptly stopped.
- Hormonal disturbances: osteoporosis with chronic over‑replacement.
- Miscellaneous
- Skin rash (hypersensitivity).
- Menstrual irregularities.
Monitoring
| Test | Frequency | Target Range | |
| TSH | Every 6–8 weeks after dose change; baseline pre‑treatment. | 0.4–4.5 mIU/L (adjust for pregnancy). | |
| Free T4 | 6–8 weeks post‑dose change; baseline. | 0.8–1.8 ng/dL (varies with assay). | |
| Free T3 | Not routinely monitored unless symptomatic. | 2–4 pg/mL. | |
| HbA1c | In diabetic patients. | 10 yr or pre‑existing osteoporosis. | DEXA scan annually if risk factors. |
| Cardiac assessment | Baseline and annually if cardiac history. | ECG/HF evaluation. |
Clinical Pearls
- Consistency beats dose: A stable TSH is more important than hitting a “magic number”.
- Take it with coffee? ❌ Avoid coffee or caffeinated drinks within 2 h; they compete for intestinal uptake.
- Travel wisely: If flying, maintain the regular schedule; the 12‑h lag rule applies—if the flight delays you, skip the dose and resume daily on the next full day.
- Pediatric advantage: Use liquid levothyroxine for infants; it bypasses formulation changes and reduces gastric irritation.
- Pregnancy vigilance: Women becoming pregnant should double‑check their TSH level each trimester; over‑replacement can harm fetal neurodevelopment.
- Food interactions: High‑fiber cereals, magnesium‑rich breakfast cereals, and fortified cereals should be eaten more than 12 h after the dose to prevent absorption impairment.
- Re‑check before surgery: In patients scheduled for cardiac or endocrine surgery, confirm therapeutic levels 48–72 h before the procedure to avoid peri‑operative thyroid storm.
- Autoimmune interplay: In Hashimoto’s patients, concomitant vitamin D deficiency can exacerbate autoimmune activity—consider simultaneous supplementation.
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• *This drug card incorporates current consensus guidelines, evidence‑based dosing strategies, and practical workflow tips to facilitate accurate management of levothyroxine therapy in diverse clinical contexts.*