Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS)
Abstract
OBJECTIVE: The aim of this study was to determine the extent of drug interactions affecting levothyroxine, using study drugs often co-administered to patients on long-term levothyroxine therapy. DESIGN: A retrospective population analysis linking biochemistry and prescription data between 1 January 1993 and 31 December 2012 was used. PATIENTS: The study population was Tayside residents prescribed levothyroxine on at least three occasions, within a six-month period, prior to the start of a study drug. Individuals acted as their own controls pre- and postinitiation of study drug. Overall, 10 999 patients (mean age 58 years, 82% female) being treated with thyroxine were included in the study. MEASUREMENTS: Changes in TSH following initiation of study drug. RESULTS: Iron, calcium, proton pump inhibitors and oestrogen all increased serum TSH concentration: an increase of 0·22 mU/l (P < 0.001), 0·27 mU/l (P < 0·001), 0·12 mU/l (P < 0·01), and 0·08 mU/l (P < 0·007), respectively. For these four study drugs, there was a clinically significant increase of over 5 mU/l in serum TSH, in 7·5%, 4·4%, 5·6% and 4·3% patients, respectively. There was a decrease of 0·17 mU/l (P-value 0.01) in the TSH concentration for those patients on statins. The TSH decreased by 5 mU/l in 3·7% of patients. There was no effect with H2 receptor antagonists or glucocorticoids. CONCLUSION: This large population-based study demonstrates significant interaction between levothyroxine and iron, calcium, proton pump inhibitors, statins and oestrogens. These drugs may reduce the effectiveness of levothyroxine, and patients' TSH concentrations should be carefully monitored.
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Patients with decreased gastric acid secretion due to proton pump inhibitor use may need higher LT4 doses to achieve target TSH levels.
“several studies have demonstrated that patients with decreased gastric acid secretion, owed to the use of proton pump inhibitors (PPIs), may need higher LT4 doses to achieve target TSH levels”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [78]
Long-term PPI administration presents a heightened risk in patients with decreased gastric acid secretion who need higher LT4 doses.
“long-term PPI administration presenting a heightened risk in these cases (47, 78).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [78]
The leading cause of refractory hypothyroidism is interfering medications, since more than 50% of LT4-treated patients are concurrently taking more than 1 drug for other medical conditions.
“The leading cause of refractory hypothyroidism is interfering medications, since more than 50% of LT4-treated patients are concurrently taking >1 drug for other medical conditions (8).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [8]
The most frequently prescribed concomitant drugs were statins, PPIs, and calcium and iron supplements.
“The most frequently prescribed concomitant drugs were statins, PPIs, and calcium and iron supplements (8, 71).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [8]
In the same Scottish study, TSH decreased significantly (0.17 mU/L) in patients on statins and changed insignificantly in patients on H2 receptor antagonists or glucocorticoids.
“TSH decreased significantly (0.17 mU/L) in patients on statins and changed insignificantly in patients on H2 receptor antagonists or glucocorticoids (25).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [25]
In 10,999 Scottish residents prescribed L-T4 before starting interfering medications, iron, calcium, proton-pump inhibitors, and estrogens increased TSH significantly, with an increase >5 mU/L in 7.5%, 4.4%, 5.6%, and 4.3% of patients, respectively.
“A retrospective study evaluated TSH changes in 10,999 Scottish residents who were prescribed L-T4 before starting IM (25). Iron, calcium, PPI, and estrogens increased TSH significantly, with an increase >5 mU/L in 7.5, 4.4, 5.6, and 4.3% patients, respectively.”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [25]
Not all L-T4-replaced hypothyroid patients taking interfering medications become undertreated.
“The Scottish study (25) is important because it reminds that not all L-T4-replaced hypothyroid patients taking IM become undertreated.”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [25]
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BackgroundInfluentialIdentifying predictors of prolonged levothyroxine dose adjustment after thyroidectomy
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- Authors
- A. Irving, S., Vadiveloo, T., & Leese, G. P.
- Affiliations
- Department of Endocrinology Ninewells Hospital Dundee UK
- Ninewells Hospital (GB)
- Corresponding author
- Leese, Graham P.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2014-08-14
- Volume
- 82
- Issue
- 1
- Pages
- 136-141
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2159449151
- Cited by
- 69
- References
- 27
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 1
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- NHS Tayside
- 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 interactions, thyroid-stimulating hormone, iron, calcium, proton pump inhibitors, statins, estrogen, H2 receptor antagonists, glucocorticoids, thyroid function monitoring, hypothyroidism
- MeSH terms
- Adult, Aged, Drug Interactions, Female, Humans, Male, Middle Aged, Drug Prescriptions, Scotland, Thyrotropin, Thyroxine
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