Drug interactions with levothyroxine therapy in patients with hypothyroidism: observational study in general practice
Abstract
Background and objectives Several drugs may interact with levothyroxine and reduce its bioavailability. The aim of this study was to analyse the Italian general practice patients with hypothyroidism from 2002-2011, in terms of variation of thyroid-stimulating hormone (TSH) levels, number of levothyroxine prescriptions and dose of levothyroxine before and during potential drug-drug interactions (DDIs).Methods Data were extracted from the Italian general practice Health Search CSD Longitudinal Patient Database (HSD). Analysis was limited to individuals aged 18 years and older with at least one levothyroxine prescription from 2002 to 2011 and at least one year of clinical history recorded in HSD. A quasi-experimental pre-post analysis was carried out using a self-controlled study design, on an intention-to-treat basis.Results Overall, 5,426 levothyroxine users (7.5 % of population in HSD) were included in the study. The incidence rate ratio comparing the TSH trend before and during the period of exposure to potential DDI showed a significant increase of TSH levels during initial exposure to potential DDI, which decreased over time. The number of prescriptions and dose of levothyroxine decreased before the potential DDI and increased symmetrically during the period of exposure to potential DDI.Conclusions The co-prescription of levothyroxine and potentially interacting drugs results in an increased use of levothyroxine. Clinicians should carefully consider adjusting levothyroxine therapy in presence of concomitant drugs, such as proton-pump inhibitors, which may reduce levothyroxine bioavailability.
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In 5,426 L-T4 users aged ≥18 years, prescriptions and doses of L-T4 increased during exposure to potential drug-drug interactions by 6% and 5%, respectively.
“In 5,426 L-T4 users aged ≥18 years (7.5% of persons under care), prescriptions and doses of L-T4 increased during exposure by 6 and 5%, respectively, suggesting that clinicians increase the number of L-T4 prescriptions to achieve TSH levels as low as those before DDIs (24).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [24]
A high proportion of LT4-treated patients ingest medications, foodstuffs, and food supplements that selectively or specifically reduce intestinal absorption of LT4.
“Furthermore, a high proportion of LT4-treated patients ingest medications, foodstuffs and food supplements that selectively or specifically reduce the intestinal absorption of LT4.”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [63]
There is a large body of evidence that PPIs are prominent interfering substances that raise TSH levels and/or LT4 dose requirement.
“There is a large body of evidence (from general practice patient databases, electronic medical record reviews, and clinical trials) to indicate that PPIs are prominent interfering substances that raise TSH levels and/or the LT4 dose requirement [ 63 , 72 , 73 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [63]
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References 33 · Cited by 40
- Authors
- Trifirò, G., Parrino, F., Sultana, J., Giorgianni, F., Ferrajolo, C., Bianchini, E., Medea, G., Benvenga, S., Cricelli, I., Cricelli, C., & Lapi, F.
- Affiliations
- University of Messina (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Società Italiana di Medicina Generale (IT)
- Corresponding author
- Trifirò, Gianluca
- ORCID
- Venue
- Clinical Drug Investigation
- Published
- 2015-02-03
- Volume
- 35
- Issue
- 3
- Pages
- 187-195
- ISSN
- 0114-2402 (ISSN-L)
- 1173-2563
- 1179-1918
- OpenAlex
- W2069238297
- Cited by
- 40
- References
- 33
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 6 · 2015: 1
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Clinical Drug Investigation (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- levothyroxine, drug-drug interactions, hypothyroidism, thyroid-stimulating hormone, proton pump inhibitors, levothyroxine dose adjustment, thyroid hormone replacement, general practice patients
- MeSH terms
- Drug Interactions, Female, Humans, Hypothyroidism, Male, Middle Aged, Thyroxine, Multivariate Analysis, General Practice
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