Real world evidence in effectiveness, safety, and cost savings of generic levothyroxine: a systematic review
Abstract
Purpose Generic levothyroxine, approved through Abbreviated New Drug Application (ANDA), is available for generic substitution. But ANDA does not require nonclinical or clinical data to establish safety and efficacy. Post-marketing evidence in generic equivalence for marketed levothyroxine products is limited. We conducted a systematic review to synthesize evidence in effectiveness, safety, and cost savings between patients using generic and branded levothyroxine.Methods We systematically searched published literature from Medline, International Pharmaceutical Abstracts, APA PsycInfo, and CINAHL from inception through 04/18/2021. Included studies were limited to post-marketing empirical studies including patients who used levothyroxine products, with direct comparison between generic and brand levothyroxine, and published in English. Risk of bias was assessed using the National Institute of Health Study Quality Assessment Tools. Two reviewers independently extracted data and conducted quality assessment for included studies. Given that the nine studies are so diverse, a meta-analysis was not possible. Therefore we provided a narrative review of the included studies.Results Of 349 studies identified, nine met the inclusion criteria. Six studies compared thyrotropin levels and adverse events between generic and brand users and provided mixed findings. In addition, generic users may generate prescription cost savings for payers but had suboptimal medication adherence than brand users.Conclusion Findings from this systematic review highlighted the limited and mixed evidence in real-world clinical and economic outcomes for generic levothyroxine. Continuous post-marketing monitoring and assessment of generic drugs are warranted to ensure treatment effectiveness, patient safety, and achieve financial savings in prescription costs.
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Other studies found switching among generics is associated with clinically significant changes in TSH level.
“but not for others (28, 37, 39, 40).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [37]
Generic levothyroxine is available for treatment of hypothyroidism; potency can vary from manufacturer to manufacturer, and there is uncertainty whether patient will receive same generic drug from same manufacturer each time.
“Generic levothyroxine is available for the treatment of hypothyroidism; however, potency can vary from manufacturer to manufacturer, and there is also uncertainty as to whether the patient will receive the same generic drug from the same manufacturer each time (37).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [37]
A systematic review concluded there is limited and mixed evidence in real-world clinical and economic outcomes for generic levothyroxine.
“The conclusion of a systematic review highlighted ‘the limited and mixed evidence in real-world clinical and economic outcomes for generic levothyroxine’ (37).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [37]
Hypothyroid treatment not covered by insurance typically costs €15-€50 per month or €180-€600 per year, depending on dosage, form, country, and brand name.
“More specifically, hypothyroid treatment that is not covered by insurance typically costs €15–€50 per month or €180–€600 per year, depending on the dosage, form, country, and brand name (35, 36, 37, 38, 39).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [37]
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“The conclusion of a systematic review highlighted ‘ the limited and mixed evidence in real-world clinical and economic outcomes for generic levothyroxine ’ (37).”
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- Authors
- Qian, J., & Tanni, K. A.
- Affiliations
- Auburn University (US)
- Corresponding author
- Qian, Jingjing
- Venue
- Endocrine
- Published
- 2021-07-28
- Volume
- 74
- Issue
- 2
- Pages
- 228-234
- ISSN
- 0969-711X (ISSN-L)
- 1355-008X
- 1559-0100
- OpenAlex
- W3183722222
- Cited by
- 2
- References
- 23
- Citations by year
- 2025: 1 · 2023: 1
- FWCI
- 0.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- levothyroxine, generic substitution, abbreviated new drug application, post-marketing surveillance, thyroid hormone replacement, adverse events, medication adherence, drug safety and efficacy
- MeSH terms
- Humans, Thyroxine, Drugs, Generic, Treatment Outcome, Cost Savings, Medication Adherence
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