Introduction
Euthyrox (levothyroxine sodium) is a synthetic thyroid hormone replacement medication used to treat hypothyroidism and other thyroid conditions. As the sodium salt of the natural thyroid hormone thyroxine (T4), it represents the standard of care for thyroid hormone replacement therapy worldwide.
Mechanism of Action
Euthyrox exerts its effects through replacement of endogenous thyroid hormones. Levothyroxine (T4) is converted to triiodothyronine (T3) in peripheral tissues via deiodination. Thyroid hormones then bind to nuclear receptors and regulate gene expression, influencing metabolic processes throughout the body including:
- Basal metabolic rate
- Carbohydrate, protein, and lipid metabolism
- Growth and development
- Thermogenesis
- Cardiac function
- Neurological function
Indications
- Treatment of hypothyroidism
- Thyroid stimulating hormone (TSH) suppression in:
- Management of well-differentiated thyroid cancer - Treatment of euthyroid goiters
- Myxedema coma (high-dose intravenous formulation)
- Diagnostic tool in thyroid suppression tests
Dosage and Administration
Initial dosing:- Healthy adults <50 years: 1.6 mcg/kg/day
- Elderly or cardiac disease: 12.5-25 mcg/day with gradual titration
- Congenital hypothyroidism: Pediatric dosing based on body weight and age
- Take on empty stomach, 30-60 minutes before breakfast
- Consistent timing daily
- Avoid concomitant administration with calcium, iron, or antacids (separate by 4 hours)
- Pregnancy: Requirements typically increase by 25-50%
- Elderly: Start with lower doses (12.5-25 mcg/day)
- Renal impairment: No dosage adjustment typically needed
- Hepatic impairment: Use with caution; may affect conversion
Pharmacokinetics
Absorption: Incomplete and variable (40-80%) from GI tract, primarily in jejunum and ileum Distribution: Highly protein-bound (>99%) to thyroid-binding globulin, prealbumin, and albumin Metabolism: Hepatic deiodination to T3 (active) and reverse T3 (inactive) Elimination: Primarily fecal excretion via biliary elimination; half-life approximately 7 days Onset of action: 3-5 days; full therapeutic effect may take 4-6 weeksContraindications
- Untreated subclinical or overt thyrotoxicosis
- Uncorrected adrenal insufficiency
- Acute myocardial infarction
- Hypersensitivity to any component of the formulation
- Untreated pituitary or hypothalamic disorders
Warnings and Precautions
Cardiac effects: May exacerbate angina pectoris or precipitate arrhythmias in patients with cardiovascular disease Osteoporosis: Long-term supraphysiologic doses may accelerate bone loss in postmenopausal women Adrenal insufficiency: May precipitate adrenal crisis in patients with uncontrolled adrenal insufficiency Diabetes mellitus: May worsen glycemic control; monitor blood glucose closely Elderly patients: Increased risk of atrial fibrillation and other cardiac complicationsDrug Interactions
Significant interactions:- Antacids, calcium, iron, cholestyramine: Decreased absorption (separate by 4 hours)
- Estrogens: May increase thyroid-binding globulin, requiring dose adjustment
- Warfarin: Enhanced anticoagulant effect (monitor INR closely)
- Antidiabetic agents: May require dosage adjustment
- Digoxin: Reduced serum digoxin levels
- Ketamine: May precipitate hypertension and tachycardia
- Tricyclic antidepressants: Mutual potentiation of effects
- CYP450 inducers (phenobarbital, rifampin, carbamazepine): May increase levothyroxine metabolism
Adverse Effects
Common effects (usually dose-related):- Palpitations
- Tachycardia
- Tremors
- Headache
- Insomnia
- Increased appetite
- Weight loss
- Heat intolerance
- Menstrual irregularities
- Cardiac arrhythmias
- Angina pectoris
- Myocardial infarction
- Heart failure
- Thyroid storm (with overdose)
- Adrenal crisis
Monitoring Parameters
- TSH: Primary monitoring parameter (target range individualized)
- Free T4: Useful in certain clinical situations
- Total T3: Occasionally helpful
- Clinical symptoms of hypo/hyperthyroidism
- Vital signs (especially heart rate and blood pressure)
- Bone mineral density (with long-term supraphysiologic dosing)
- Lipid profile
- Cardiac function in elderly or cardiac patients
Patient Education
- Take medication consistently at the same time each day
- Administer on empty stomach, 30-60 minutes before food
- Do not switch between brand names without medical supervision
- Report symptoms of hyperthyroidism (palpitations, sweating, nervousness) or hypothyroidism (fatigue, weight gain, cold intolerance)
- Inform all healthcare providers about thyroid medication use
- Do not discontinue medication without medical advice
- Keep regular follow-up appointments for monitoring
- Separate from calcium, iron, and antacids by at least 4 hours
- Pregnancy: Notify physician immediately if pregnant or planning pregnancy
References
1. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751. 2. FDA Prescribing Information: Euthyrox (levothyroxine sodium) tablets. 3. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988-1028. 4. Wiersinga WM, Duntas L, Fadeyev V, et al. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. Eur Thyroid J. 2012;1(2):55-71. 5. Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018;14(5):301-316.