Levothyroxine dosage and the limitations of current bioequivalence standards
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Chemical equivalence does not automatically correspond to bioequivalence, which is determined by pharmacokinetic tests on healthy volunteers but may differ from actual bioequivalence in patients in different clinical settings.
“However, it is known that chemical equivalence does not automatically correspond to bioequivalence, which is determined by pharmacokinetic tests on healthy volunteers (28) but may differ from actual bioequivalence in patients in different clinical settings (29).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [28]
Adherence to a LT4 preparation results in significantly reduced hypothyroidism-related non-drug medical costs and hypothyroidism-related total medical costs.
“Moreover, adherence to a LT4 preparation results in significantly reduced hypothyroidism-related non-drug medical costs and hypothyroidism-related total medical costs (28, 40).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [28]
l-T4 preparations of different brands cannot be considered bioequivalent.
“l-T4 preparations of different brands cannot be considered bioequivalent (39, 40).”
From Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research (2016) · cites this paper as [39]
Other studies found switching among generics is associated with clinically significant changes in TSH level.
“but not for others (28, 37, 39, 40).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [28]
Owing to uncertainties regarding levothyroxine bioequivalence of certain generics to branded compounds, some variation in patients' TSH levels was observed.
“Owing to some uncertainties regarding the levothyroxine bioequivalence of certain generics to that of branded compounds, some variation in patients’ TSH levels were observed (28, 39, 40).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [28]
Indirect costs of changing brand or formulations (medical costs and higher consumption of healthcare resources) have been recognized.
“In addition, the indirect costs of changing brand or formulations (medical costs and higher consumption of healthcare resources) has been recognized ((28, 36), this latter study was funded by industry).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [28]
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Henderson, J. D., & Esham, R. H. (2001) · PubMed · Cited by 47 · see citing works
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Levothyroxine a New Drug? Since When? How Could That Be?
Hennessey, J. (2003) · Thyroid · doi:10.1089/105072503321582088 · Cited by 29 · see citing works
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Hypothyroidism: etiology, diagnosis, and management
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Timing of levothyroxine administration affects serum thyrotropin concentration
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“Moreover, -T4 preparations of different brands cannot be considered bioequivalent (39, 40).”
BackgroundDevelopment of the generic drug industry in the US after the Hatch-Waxman Act of 1984
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Thyroxine and treatment of hypothyroidism: seven decades of experience
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Levothyroxine Formulations: Pharmacological and Clinical Implications of Generic Substitution
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TSH-Based Protocol, Tablet Instability, and Absorption Effects on L-T <sub>4</sub> Bioequivalence
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The FDA Revises Requirements for Levothyroxine Products
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7 Medical Management of Thyroiditis and Hypothyroidism
(2021) · Thieme Medical Publishers eBooks · doi:10.1055/b-0041-182782
- Authors
- Hennessey, J. V.
- Affiliations
- Brown University (US)
- Corresponding author
- Hennessey, James V
- ORCID
- Hennessey, James V
- Venue
- Nature Clinical Practice Endocrinology & Metabolism
- Published
- 2006-09
- Volume
- 2
- Issue
- 9
- Pages
- 474-475
- ISSN
- 1745-8366 (ISSN-L)
- 1745-8374
- OpenAlex
- W2078365441
- Cited by
- 28
- References
- 5
- Citations by year
- 2025: 1 · 2021: 2 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 4 · 2012: 3
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Clinical Practice Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- levothyroxine, dosage, bioequivalence, therapeutic equivalence, pharmacokinetics, generic drugs, FDA regulation, thyroid hormone replacement
- MeSH terms
- Biological Availability, Dose-Response Relationship, Drug, Drug Therapy, Humans, Therapeutic Equivalency, Thyrotropin, Thyroxine, United States, United States Food and Drug Administration
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