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Cited by 29Thyroid Disorders and TreatmentsPharmacogenetics and Drug MetabolismPharmacy and Medical Practices

Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review

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Liu, Hanqing, Lu, Man, Hu, Jiawei, Fu, Guangzhao, Feng, Qinyu, Sun, Shengrong, Chen, Chuang·2023·Therapeutics and Clinical Risk Management
DOI 10.2147/tcrm.s414460PMC PMC10295503
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Abstract

Purpose: Levothyroxine is a common prescribed drug. Many medications and food, however, can interfere with its bioavailability. The aim of this review was to summarize the medications, food and beverages that interact with levothyroxine and to assess their effects, mechanisms and treatments. Methods: A systematic review on interfering substances that interact with levothyroxine was performed. Web of Science, Embase, PubMed, the Cochrane library, grey literature from other sources and the lists of references were searched for human studies comparing the levothyroxine efficacy with and without interfering substances. The patient characteristics, drug classes, effects and mechanism were extracted. The NHLBI study quality assessment tools and the JBI critical appraisal checklist were used to assess the quality of included studies. Results: A total of 107 articles with 128 studies were included. Drugs interactions were revealed in calcium and iron supplements, proton pump inhibitors, bile acid sequestrants, phosphate binders, sex hormones, anticonvulsants and other drugs. Some food and beverage could also induce malabsorption. Proposed mechanisms included direct complexing, alkalization, alteration of serum thyroxine-binding globulin levels and acceleration of levothyroxine catabolism via deiodination. Dose adjustment, administration separation and discontinuation of interfering substances can eliminate the interactions. Liquid solutions and soft-gel capsules could eliminate the malabsorption due to chelation and alkalization. The qualities of most included studies were moderate. Conclusion: Lots of medications and food can impair the bioavailability of levothyroxine. Clinicians, patients and pharmaceutical companies should be aware of the possible interactions. Further well-designed studies are needed to provide more solid evidence on treatment and mechanisms.

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Crossref · 10.2147/tcrm.s414460

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  • Most commonly prescribed drugs act by sequestrating the hormone in the intestinal content, considerably decreasing LT4 bioavailability.

    “Most of the commonly prescribed drugs act by sequestrating the hormone in the intestinal content, thus considerably decreasing LT4 bioavailability.”

    From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [84]

    The Results section, “Medications Binding with LT4” (page not supplied), says some medications bind LT4 and inhibit its absorption. But the Introduction identifies statins and proton pump inhibitors among the most frequently prescribed concomitant drugs, and the Results describes mechanisms other than intestinal binding for both. The review therefore supports sequestration as one mechanism, not the claim that most commonly prescribed drugs act this way. (LLM, conf=0.88)

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  • Co-prescription of LT4 with several interacting drugs or supplements can frequently lead to decreased LT4 bioavailability, which may often be clinically relevant.

    “In conclusion, the co-prescription of LT4 with several interacting drugs or supplements can frequently lead to decreased LT4 bioavailability, which may often be clinically relevant (84).”

    From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [84]

  • Estrogens, raloxifene, and carbamazepine can affect levothyroxine transport in the circulation.

    “Estrogens, raloxifene, and carbamazepine can affect LT4 transport in circulation.”

    From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [54]

  • Carbamazepine, fluoxetine, sertraline, sorafenib, mifepristone, phenytoin, statins, and protease inhibitors can alter levothyroxine catabolism.

    “Additionally, there are medications that alter LT4 catabolism, such as carbamazepine, fluoxetine, sertraline, sorafenib, mifepristone, phenytoin, statins, and protease inhibitors.38,54”

    From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [54]

  • Ciprofloxacin and rifampin alter transmembrane transport, while proton pump inhibitors and histamine H2 receptor agonists can change gastric pH.

    “Other medications alter transmembrane transport, such as ciprofloxacin and rifampin.Proton pump inhibitors (PPIs) and histamine H2 receptor agonists can modify gastric pH.”

    From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [54]

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Research works printed but not linked: 7

  1. [11]May K, Meng W, Warzok R, et al. Is thyroxine malabsorption caused by autoinduction of intestinal P-glycoprotein? A case report. Naunyn-Schmiedebergs Archiv Pharmacol. 2002; 365: R109– R109.
  2. [12]Nobre EL, Jorge Z, Anselmo J, et al. A rare case of malabsorption of thyroid hormones. Ma absorcao das hormonas tiroideias. Acta Med Port. 2004; 17(6): 487– 491. 16197861
  3. [48]Gormley GJ, Tobert JA. Drug-interaction between thyroxine and lovastatin - reply. N Engl J Med. 1989; 321(19): 1342. 2797109
  4. [58]Cappelli C, Rotondi M, Pirola I, et al. TSH-lowering effect of metformin in type 2 diabetic patients differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care. 2009; 32(9): 1589– 1590. doi: 10.2337/dc09-0273 19502536 PMC2732148 · DOI · Paper page
  5. [73]Sahajpal R, Ahmed RA, Hughes CA, Foisy MM. Probable interaction between levothyroxine and ritonavir: case report and literature review. Am J Health Syst Pharma. 2017; 74(8): 587– 592. doi: 10.2146/ajhp160200 28389458 · DOI · Paper page
  6. [90]Antúnez PB, Licht SD. Vitamin C improves the apparent absorption of levothyroxine in a subset of patients receiving this hormone for primary hypothyroidism. La vitamina C mejora la absorción aparente de levotiroxina en ciertos pacientes que reciben esta hormona por hipotiroidismo primario. Revista argentina de endocrinología y metabolismo. 2011; 48(1): 16– 24.
  7. [94]Lamson MJ, Pamplin CL, Rolleri RL, Klein I. Quantitation of a substantial reduction in levothyroxine (T4) absorption by food. Thyroid. 2004; 14(10): 873– 876. doi: 10.1089/thy.2004.14.873 · DOI

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Authors
Liu, H., Lu, M., Hu, J., Fu, G., Feng, Q., Sun, S., & Chen, C.
Affiliations
  • Renmin Hospital of Wuhan University (CN)
  • Zhongnan Hospital of Wuhan University (CN)
Corresponding author
Chen, Chuang
ORCID
Venue
Therapeutics and Clinical Risk Management
Publisher
Informa UK Limited
Published
2023-06
Volume
Volume 19
Pages
503-523
ISSN
  • 1176-6336 (ISSN-L)
  • 1178-203X
DOI
10.2147/tcrm.s414460
PMC
PMC10295503
OpenAlex
W4381801314
Cited by
29
References
132
Citations by year
2026: 13 · 2025: 10 · 2024: 3 · 2023: 3
FWCI
1.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Therapeutics and Clinical Risk Management (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Beijing Xisike Clinical Oncology Research Foundation (Y‐SY201901‐0189)
  • Fundamental Research Funds for the Central Universities (2042019kf0229)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacy and Medical Practices
Keywords
levothyroxine, drug interactions, food interactions, bioavailability, proton pump inhibitors, bile acid sequestrants, phosphate binders, sex hormones, antiepileptic drugs, malabsorption, thyroxine-binding globulin, deiodination, dose adjustment, administration timing, chelation, alkalization

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