A new formulation of levothyroxine engineered to meet new specification standards
Abstract
Background: Small variations in the dose of levothyroxine have been associated with marked variations in thyroid function in people with hypothyroidism. Accordingly, regulators have identified levothyroxine as a “narrow therapeutic index” drug subject to more stringent regulations compared with other drugs, in terms of the accuracy and stability of the amount of active drug in each tablet (typically required to be 95–105% of the labelled amount over its full shelf life), and its bioavailability geometric mean ratios (90% confidence intervals between 90–111.1%, including 100%).Review: This review describes a reformulation of a widely used levothyroxine product (Euthyrox.*). The new tablet fulfils all criteria according to the new specification regulations for dosage accuracy over a shelf life of 3 years in all climate zones, and for bioequivalence compared to the conventional formulation used for many years. In addition, a clinical trial demonstrated equivalent exposure between three different tablet strengths of the new formulation, amounting to the same total dose (dose form proportionality). As a consequence, switching from the conventional to the new formulation can be undertaken on a 1:1 dose-for-dose basis, without re-titration or additional thyroid function testing.Conclusion: The new formulation, which is more stable, will assist in the accurate dosage and titration of levothyroxine in the management of hypothyroidism.
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A number of studies have evaluated the interchangeability of LT4 among manufacturers, brands, or batches, and the results are controversial.
“A number of studies have evaluated the interchangeability of LT4 among manufacturers, brands, or batches (106–108), and the results are controversial.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [107]
Normally, the bioequivalence of LT4 remains unchanged over a shelf life of more than 36 months.
“Normally, the bioequivalence remains unchanged over a shelf life of more than 36 months (107).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [107]
Thyroid hormones have a narrow therapeutic index.
“Thyroid hormones have a narrow therapeutic index 4 .”
From A review of the safety of triiodothyronine in combination with levothyroxine for the management of hypothyroidism (2024) · cites this paper as [4]
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Sonane, P. R., Sathala, P. K., Rathod, M., Chenkaul, L., Lalchandani, D. S., Dewangan, A., & Porwal, P. K. (2025) · Journal of Thermal Analysis and Calorimetry · doi:10.1007/s10973-025-14986-z
- Authors
- Lipp, H.-P., & Hostalek, U.
- Affiliations
- Universitätsklinikum Tübingen (DE)
- Global Medical Affairs, Merck KGaA, Darmstadt, Germany
- Venue
- Current Medical Research and Opinion
- Publisher
- Informa UK Limited
- Published
- 2018-11-26
- Volume
- 35
- Issue
- 1
- Pages
- 147-150
- ISSN
- 0300-7995 (ISSN-L)
- 1473-4877
- OpenAlex
- W2899749134
- Cited by
- 19
- References
- 17
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 2
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Medical Research and Opinion (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- levothyroxine, drug reformulation, hypothyroidism, bioequivalence, dose accuracy, drug stability, narrow therapeutic index, thyroid function, bioavailability
- MeSH terms
- Biological Availability, Humans, Hypothyroidism, Tablets, Therapeutic Equivalency, Thyroxine
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