Are Synthroid (levothyroxine) and levothyroxine the same medication?

Synthroid and Levothyroxine: Same Active Ingredient, Different Formulations

Yes, Synthroid and levothyroxine are the same medication—both contain the identical active ingredient, synthetic levothyroxine sodium (L-thyroxine/T4), which is chemically identical to the hormone produced by the human thyroid gland. 1 However, Synthroid is a brand-name product while "levothyroxine" typically refers to generic formulations, and they differ in their inactive ingredients (excipients) and manufacturing processes.

Chemical Identity and Active Ingredient

• The active pharmaceutical ingredient in both Synthroid and generic levothyroxine is synthetic crystalline L-3',5'-tetraiodothyronine sodium salt, with the molecular formula C₁₅H₁₀I₄NNaO₄•H₂O 1
• This synthetic T4 is chemically identical to endogenous thyroid hormone and exerts the same physiologic effect by controlling DNA transcription and protein synthesis 1
• Both products work through the same mechanism: T4 diffuses into cell nuclei, binds to thyroid receptor proteins attached to DNA, and activates gene transcription 1

Bioequivalence Evidence

Current FDA standards demonstrate that approved generic levothyroxine products are bioequivalent to brand-name Synthroid, meaning they are clinically interchangeable for the majority of patients. 2

• A rigorous 1997 JAMA study comparing Synthroid, Levoxine (now Levoxyl), and two generic preparations found relative bioequivalence of 0.95 to 1.07—tighter than the FDA's standard bioequivalence criterion of 0.8 to 1.25 2
• No significant differences were found in area under the curve, peak serum concentrations of total thyroxine, total triiodothyronine, or free thyroxine index among the four products 2
• A 2013 study in children with congenital hypothyroidism found that generic levothyroxine resulted in similar or better control compared to Synthroid, with lower TSH variance and similar frequency of dose adjustments 3
• A 1995 prospective study using third-generation TSH assays found no statistically significant differences in clinical scores, free thyroxine index, basal TSH levels, or TRH response when patients were switched between Synthroid and Levoxine 4

Key Differences: Inactive Ingredients

While the active ingredient is identical, the formulations differ in their inactive excipients:

• Generic levothyroxine tablets contain microcrystalline sodium, light magnesium oxide, sodium starch glycolate, and sodium stearyl fumarate 1
• Different manufacturers use varying color additives for different tablet strengths 1
• These differences in inactive ingredients can theoretically affect absorption rates in individual patients, though bioequivalence studies demonstrate this is not clinically significant for most patients 2

Clinical Implications for Switching

For the vast majority of patients, switching between Synthroid and generic levothyroxine is safe and appropriate, but monitoring is essential due to levothyroxine's narrow therapeutic index. 5

• Levothyroxine has a narrow therapeutic index, meaning small changes in absorption can potentially affect clinical outcomes 5
• Both underdosage (subclinical hypothyroidism) and excessive dosage (subclinical hyperthyroidism) are associated with adverse symptoms and must be avoided 5
• When switching between formulations, recheck TSH and free T4 in 6-8 weeks to ensure therapeutic levels remain stable 6, 7
• The long half-life of approximately 7 days means steady-state concentrations are achieved in 6-8 weeks, requiring this monitoring interval 7

Historical Quality Control Issues

• A 1984 study found that Synthroid tablets contained 20-30% less thyroxine than their stated content, resulting in decreased bioavailability and biologic action 8
• This historical issue prompted FDA requirements for new drug applications for all levothyroxine products to ensure consistent potency 5
• Modern manufacturing standards and FDA oversight have largely resolved these historical quality concerns 5

Important Caveats

• While bioequivalence has been demonstrated for studied products, not all existing levothyroxine preparations have been rigorously compared 2
• Individual patients may experience differences when switching due to variations in absorption, particularly those with malabsorption syndromes or taking medications that affect T4 absorption 1
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, highlighting the importance of monitoring regardless of which formulation is used 6
• Patients should ideally remain on the same manufacturer's product once stable to minimize variability, though switching is generally safe with appropriate monitoring 5