Two Cases of Therapeutic Failure Associated with Levothyroxine Brand Interchange
Abstract
OBJECTIVE: To report the loss of therapeutic control in 2 hypothyroid patients and remind clinical pharmacists and other healthcare professionals to remain cognizant of possible product quality differences within or bioequivalency differences between levothyroxine products. CASE SUMMARIES: Two patients with stable hypothyroidism experienced symptoms of hypothyroidism with increased serum thyroid-stimulating hormone (TSH) concentrations after switching from 1 levothyroxine product to another. One tablet from 1 of the patient's levothyroxine prescriptions was assayed, and its levothyroxine content was 74.5% of the label claim, a value outside of the United States Pharmacopeia requirements of 90-110%. DISCUSSION: Two patients with hypothyroidism had remained euthyroid and stable while receiving 1 levothyroxine product, but became symptomatic with dramatically increased serum TSH concentrations while receiving what were thought to be comparable dosages of another levothyroxine product. Therapeutic control was reestablished in both patients after therapy with the original levothyroxine product was reinstated. CONCLUSIONS: Clinical pharmacists and other healthcare professionals should remain cognizant of possible product quality differences within or bioequivalency differences between levothyroxine products. These differences necessitate close monitoring of hypothyroid patients, counseling these patients about the clinical signs of sub- and supratherapeutic levothyroxine dosages, and prudence when switching patients with stable hypothyroidism to alternative levothyroxine products. If there are inconsistencies between levothyroxine products, resultant deleterious effects on the therapeutic stability of patients with hypothyroidism may undermine cost savings that might be incurred by such a change. If these patients are switched to alternative levothyroxine products, it is recommended that thyroid function tests be repeated after equilibration to the new product.
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Anecdotal reports exist of TSH changes associated with different LT4 products.
“Anecdotal reports of TSH changes associated with different LT4 products exist (170).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [170]
Changes in brands or formulations may cause TSH elevations, as supported by some reports.
“Since it is almost impossible to conduct a direct comparative analysis of the bioavailability of all products, we cannot abandon the hypothesis that changes in brands or formulations cause TSH elevations, as supported by some reports (109–111).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [110]
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Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928 · see citing works
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Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
Levothyroxine sodium pentahydrate tablets – formulation considerations
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- Authors
- Copeland, P. M.
- Affiliations
- Harvard University (US)
- Corresponding author
- Copeland, Paul M
- Venue
- Annals of Pharmacotherapy
- Publisher
- SAGE Publications
- Published
- 1995-05
- Volume
- 29
- Issue
- 5
- Pages
- 482-485
- ISSN
- 0012-6578 (ISSN-L)
- 1060-0280
- 1542-6270
- OpenAlex
- W2465068842
- Cited by
- 14
- References
- 11
- Citations by year
- 2022: 1 · 2021: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pharmaceutical Quality and Counterfeiting
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Keywords
- levothyroxine, hypothyroidism, bioequivalence, product quality, serum TSH, therapeutic drug monitoring, tablet assay, thyroid function tests, cost reduction
- MeSH terms
- Adult, Female, Humans, Hypothyroidism, Pregnancy, Pregnancy Complications, Therapeutic Equivalency, Thyrotropin, Thyroxine, Drugs, Generic
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