Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
Abstract
Purpose Levothyroxine (LT4) is a drug with a narrow therapeutic index, applied in small amounts (micrograms), which makes interactions in the absorption phase clinically significant. The main aim of this article was to review and present the latest information on factors that affect the gastrointestinal absorption of this drug.Methods Relevant data were collected by using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words levothyroxine and absorption. Searches were not limited to specific publication types, study designs, dates, or languages. The reports were highly variable in the amount of information provided regarding study design and methods. Because of the heterogeneity of studies, no statistical analysis was performed.Findings Many gastrointestinal disorders, such as celiac disease, atrophic gastritis, lactose intolerance, and Helicobacter pylori infection, may impede the absorption of levothyroxine. During treatment of these disorders, it is necessary to monitor serum thyroid-stimulating hormone and free T4 values to reduce the risk of developing iatrogenic hyperthyroidism. Soybeans and coffee have the greatest impact on the reduction of absorption, whereas vitamin C has the ability to increase it. Conversely, the effect of dietary fiber on the absorption of LT4 is not yet fully understood; further research is needed on this topic. A decrease in the absorption of LT4 is established and clinically significant when administered concomitantly with cholestyramine, colesevelam, lanthanum, calcium carbonate, calcium citrate, calcium acetate, iron sulfate, ciprofloxacin, aluminum hydroxide, sevelamer, or proton pump inhibitors. This effect should be taken into consideration when prescribing these drugs concomitantly with LT4. The effects of Giardia lamblia infection and the influence of orlistat, polystyrene sulfonate, raloxifene, and simethicone on absorption of LT4 have been poorly documented. For bariatric surgery, sucralfate and H 2-antagonist interactions are not well founded or contradictory evidence is available regarding their existence; additional research should be conducted.Implications The majority of the interactions are clinically significant. They are based on the LT4 adsorption on interfering substances in the digestive tract, as well as a consequently reduced amount of the drug available for absorption. These interactions can be avoided by separating the administration of LT4 and the interfering substance.
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Levothyroxine absorption takes place primarily in the duodenum and jejunum of the small intestine.
“Then, levothyroxine absorption takes place primarily in the duodenum and jejunum of the small intestine [1, 2].”
From Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With “Refractory Hypothyroidism” (2025) · cites this paper as [2]
Levothyroxine doses between 1.5 to 1.8 μg/kg/day restore clinical euthyroidism and achieve TSH values in the reference range in most patients with overt primary hypothyroidism.
“levothyroxine doses between 1.5 to 1.8 µg/kg/day restore clinical euthyroidism and achieve TSH values in the reference range in most patients with overt primary hypothyroidism.”
From Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With “Refractory Hypothyroidism” (2025) · cites this paper as [2]
Low pH in the stomach is essential for optimal dissolution and proper ionization of levothyroxine tablets.
“After oral administration, low pH in the stomach is essential for optimal dissolution and proper ionization of levothyroxine tablets.”
From Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With “Refractory Hypothyroidism” (2025) · cites this paper as [2]
In a fasted state, 60% to 80% of the orally administered levothyroxine dose is absorbed.
“In a fasted state, 60% to 80% of the orally administered levothyroxine dose is absorbed”
From Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With “Refractory Hypothyroidism” (2025) · cites this paper as [2]
Some medications, including antacids, bile acid sequestrants, and orlistat, can affect levothyroxine absorption.
“Some medications can affect LT4 absorption, such as antacids, bile acid sequestrants, and orlistat.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [38]
Lactose used as an excipient in levothyroxine tablets is unlikely to cause significant problems, since up to 400 mg lactose does not provoke gastrointestinal symptoms.
“It is unlikely that lactose used as an excipient in LT4 tablets would cause significant problems, as studies show that ingestion of up to 400 mg of lactose does not provoke gastrointestinal symptoms.38,59”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [38]
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 [38]
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 [38]
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 [38]
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Gastrointestinal malabsorption of thyroxine
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Concurrent milk ingestion decreases absorption of levothyroxine
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Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review
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Alternative routes of levothyroxine administration for hypothyroidism
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Refractory hypothyroidism: unraveling the complexities of diagnosis and management
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“Then, levothyroxine absorption takes place primarily in the duodenum and jejunum of the small intestine [1, 2].”
Refractory hypothyroidism to levothyroxine treatment: five cases of pseudomalabsorption
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- Authors
- Skelin, M., Lucijanić, T., Amidžić Klarić, D., Rešić, A., Bakula, M., Liberati-Čizmek, A.-M., Gharib, H., & Rahelić, D.
- Affiliations
- Opća bolnica Šibenik (HR)
- University Hospital Dubrava (HR)
- Children's Hospital Zagreb (HR)
- Mayo Clinic (US)
- Venue
- Clinical Therapeutics
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 39
- Issue
- 2
- Pages
- 378-403
- ISSN
- 0149-2918 (ISSN-L)
- OpenAlex
- W2580569340
- Semantic Scholar
- 1fadffe3b30511753ad7699a028b1e541abea722
- Cited by
- 133
- References
- 112
- Citations by year
- 2026: 19 · 2025: 14 · 2024: 14 · 2023: 17 · 2022: 14 · 2021: 14 · 2020: 19 · 2019: 9 · 2018: 9 · 2017: 3
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- levothyroxine, gastrointestinal absorption, drug interactions, celiac disease, atrophic gastritis, lactose intolerance, Helicobacter pylori infection, soybean, coffee, vitamin C, dietary fiber, cholestyramine, calcium carbonate, iron sulfate, ciprofloxacin, aluminum hydroxide, proton pump inhibitors, Giardia lamblia, bariatric surgery, sucralfate, H2 receptor antagonists, iatrogenic hyperthyroidism, thyroid hormone replacement
- MeSH terms
- Gastrointestinal Diseases, Humans, Intestinal Absorption, Thyrotropin, Thyroxine, Proton Pump Inhibitors
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