Impact of a forced dose-equivalent levothyroxine brand switch on plasma thyrotropin: a cohort study.
Open accessAbstract
Background: Patients with primary hypothyroidism are treated with levothyroxine (LT4) to normalize their serum thyrotropin (TSH). Finding the optimal dosage is a long-lasting process, and a small change can have major impact. Currently, limited data are available on the impact of dose-equivalent substitution between brands. This study aimed to determine the effect of the shortage of the LT4 brand Thyrax ® in the Netherlands and the resulting dose-equivalent switch to another brand on plasma TSH concentrations in a large cohort of patients. Methods: Observational cohort study. Two registries representative for the Dutch population containing prescription and laboratory test data: the Nivel Primary Care Database and the PHARMO Database Network. Patients using at least 25 μg Thyrax daily for one year or longer were included. Two cohorts were formed: a switch cohort consisting of patients who switched from Thyrax to an alternative brand, and a Thyrax cohort including patients who continued to use Thyrax. Patients in the switch cohort did switch from Thyrax to a different brand of LT4 in 2016 and had two consecutive TSH measurements on the same dose of LT4, one before and one 6 weeks after the switch. Patients in the Thyrax cohort had two consecutive TSH measurements on the same dose of Thyrax that were 6 weeks apart. Results: In the Thyrax cohort, 19% of euthyroid patients using ≤100 μg had a TSH level outside the reference range at the subsequent measurement compared with 24% in the switch cohort ( p < 0.0001). For patients using >100 μg Thyrax, these figures were 24% and 63%, respectively ( p < 0.0001). Furthermore, patients using >50 μg Thyrax were four to five times more likely to become hyperthyroid after a dose-equivalent switch to a different brand compared with patients who stayed on Thyrax. Conclusions: In euthyroid patients continuing the LT4 product Thyrax at the same dose, TSH was out of range in 19–24% at least 6 weeks later. A dose-equivalent switch from Thyrax to other LT4 brands induced biochemical signs of overdosing in an even larger proportion (24–63%) of patients. The results indicate that a dose-equivalent LT4 brand switch may necessitate a dose adjustment in a large number of patients.
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- Authors
- Flinterman, L. E., Kuiper, J. G., Korevaar, J. C., van Dijk, L., Hek, K., Houben, E., Herings, R., Franken, A. A. M., de Graaf, J. P., Horikx, A., Janssens, M., Meijer, R., Wijbenga, A., van Puijenbroek, E., Wolffenbuttel, B. H. R., Links, T. P., Bisschop, P. H., & Fliers, E.
- Affiliations
- Netherlands Institute for Health Services Research (NL)
- Pharmo Institute (NL)
- Netherlands Institute for Health Services Research, Nivel, Utrecht, The Netherlands.
- Medicines Evaluation Board (NL)
- Dutch Pituitary Foundation, Nijkerk, The Netherlands.
- Royal Dutch Pharmacists Association (NL)
- Dutch Thyroid Patient Organization (SON), Amersfoort, The Netherlands.
- Department of PharmacoTherapy, -Epidemiology and -Economics, Groningen Research Institute of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Groningen, Groningen, The Netherlands.
- University Medical Center Groningen (NL)
- Amsterdam University Medical Centers (NL)
- Corresponding author
- Korevaar, Joke C.
- ORCID
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2020-06
- Volume
- 30
- Issue
- 6
- Pages
- 821-828
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W3012080138
- Cited by
- 23
- References
- 10
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 4 · 2020: 2
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amc.nl
- Licence
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, public-domain)
- Pure Amsterdam UMC (submittedVersion, public-domain)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- ZonMw
- Ministerie van Volksgezondheid, Welzijn en Sport
- 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
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- levothyroxine, thyroid-stimulating hormone, primary hypothyroidism, drug shortages, hyperthyroidism, dose adjustment, thyroid hormone replacement, euthyroid patients, Netherlands, prescription data, laboratory test data
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Hypothyroidism, Male, Middle Aged, Thyrotropin, Thyroxine, Databases, Factual, Treatment Outcome, Hormone Replacement Therapy, Drug Substitution
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