Introduction
Synthroid (levothyroxine sodium) is a synthetic form of the endogenous thyroid hormone thyroxine (T4). It is the most commonly prescribed thyroid hormone replacement therapy and represents one of the most frequently dispensed medications in the United States. As a bioidentical hormone, Synthroid is used to manage various forms of hypothyroidism and other thyroid disorders.
Mechanism of Action
Levothyroxine sodium is a synthetic sodium salt of the natural L-isomer of thyroxine (T4). After oral administration, it is converted in peripheral tissues to the more metabolically active triiodothyronine (T3). Thyroid hormones exert their effects by binding to nuclear thyroid hormone receptors, which then regulate gene transcription and protein synthesis. This process influences metabolic rate, growth and development, temperature regulation, and numerous other physiological processes throughout the body.
Indications
- Primary, secondary, and tertiary hypothyroidism
- Thyroid hormone suppression therapy for:
- Suppression of TSH in patients with thyroid cancer - Management of benign thyroid nodules and nontoxic diffuse goiter
- Myxedema coma (requires intravenous administration)
- Congenital hypothyroidism
Dosage and Administration
Standard adult starting dose: 1.6 mcg/kg/day (typically 25-50 mcg/day) with adjustments every 4-6 weeks based on TSH levels Administration:- Take on an empty stomach, at least 30-60 minutes before breakfast
- Swallow tablets whole with water
- Consistent daily timing is essential
- Elderly patients: Start with 25-50 mcg/day
- Cardiac patients: Start with 12.5-25 mcg/day
- Pregnancy: Requirements typically increase by 25-50%
- Pediatric dosing: Based on body weight and age (consult pediatric dosing guidelines)
Pharmacokinetics
Absorption: Variable (40-80%) from the gastrointestinal tract, significantly impaired by food, coffee, and certain medications Distribution: Highly protein-bound (>99%) to thyroxine-binding globulin, prealbumin, and albumin Metabolism: Primarily deiodinated in peripheral tissues (liver, kidney, others) Elimination: Renal elimination of conjugated metabolites; elimination half-life approximately 6-7 days in euthyroid patientsContraindications
- Untreated subclinical or overt thyrotoxicosis
- Acute myocardial infarction
- Uncorrected adrenal insufficiency
- Hypersensitivity to any component of the formulation
Warnings and Precautions
- Cardiac effects: May exacerbate angina pectoris or precipitate cardiac arrhythmias in patients with cardiovascular disease
- Adrenal insufficiency: May precipitate adrenal crisis in patients with uncontrolled adrenal insufficiency
- Osteoporosis: Overtreatment may accelerate bone loss and increase fracture risk in postmenopausal women
- Elderly patients: Increased risk of atrial fibrillation and other cardiac complications
- Pregnancy: Requires careful monitoring and dose adjustments
Drug Interactions
Significant interactions that decrease levothyroxine absorption:- Calcium carbonate (and other calcium salts)
- Iron supplements
- Aluminum-containing antacids
- Proton pump inhibitors
- Bile acid sequestrants (cholestyramine, colestipol)
- Sucralfate
- Estrogens: May increase thyroxine-binding globulin and require dose adjustment
- Warfarin: Thyroid hormone may potentiate anticoagulant effect
- Antidiabetic agents: May alter glycemic control requiring dose adjustment
- Ketamine: May precipitate hypertension and tachycardia
- Tricyclic antidepressants: May increase therapeutic and toxic effects of both drugs
Adverse Effects
Common effects (usually dose-related):- Palpitations
- Tachycardia
- Increased appetite
- Nervousness
- Insomnia
- Tremor
- Headache
- Heat intolerance
- Cardiac arrhythmias
- Angina pectoris
- Myocardial infarction
- Cardiac arrest
- Heart failure
- Thyroid storm
- Psychotic manifestations
Monitoring Parameters
- TSH levels: Primary monitoring parameter, typically measured 4-8 weeks after initiation or dose change
- Free T4: Useful in certain clinical situations (pituitary disease, changing binding proteins)
- Clinical symptoms: Assessment of hypothyroid or hyperthyroid symptoms
- Vital signs: Heart rate, blood pressure, weight
- Bone mineral density: In patients receiving long-term suppressive therapy
- Cardiac status: In elderly patients and those with pre-existing cardiac disease
- Growth and development: In pediatric patients
Patient Education
- Take medication consistently on an empty stomach, 30-60 minutes before breakfast
- Do not switch between different levothyroxine brands without medical supervision
- Separate administration from calcium supplements, iron, antacids, and other interfering medications by at least 4 hours
- Report symptoms of hyperthyroidism (palpitations, excessive sweating, nervousness) or persistent hypothyroidism (fatigue, weight gain, cold intolerance)
- Adhere to regular follow-up and laboratory monitoring
- Inform all healthcare providers about thyroid medication use
- Do not discontinue medication without medical advice
- Pregnancy requires immediate medical attention for potential dose adjustment
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. 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. 3. FDA Prescribing Information: Synthroid (levothyroxine sodium) tablets. Revised 2021. 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. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27(3):315-389.