Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review.
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.



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.



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 H2-antagonist interactions are not well founded or contradictory evidence is available regarding their existence; additional research should be conducted.



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.
Pharmacy Department, General Hospital Šibenik, Šibenik, Croatia.
Marko
M
Skelin
Department of Endocrinology, Diabetes and Metabolic Disorders, Clinical Hospital Dubrava, Zagreb, Croatia.
Tomo
T
Lucijanić
Department of Health Ecology, Public Health Brčko DC, Brčko DC, Bosnia and Herzegovina. Electronic address: daniela.amidzic@gmail.com.
Daniela
D
Amidžić Klarić
Department of Paediatrics, Children's Hospital Zagreb, Zagreb, Croatia.
Arnes
A
Rešić
Department of Endocrinology, Diabetes and Metabolic Disorders, General Hospital "Sv. Duh," Zagreb, Croatia.
Miro
M
Bakula
Department of Endocrinology, Diabetes and Metabolic Disorders, General Hospital "Sv. Duh," Zagreb, Croatia.
Ana-Marija
AM
Liberati-Čizmek
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota.
Hossein
H
Gharib
Department of Endocrinology, Diabetes and Metabolic Disorders, Clinical Hospital Dubrava, Zagreb, Croatia.
Dario
D
Rahelić
D005767:Gastrointestinal Diseases / Q000503:physiopathology*; D006801:Humans; D007408:Intestinal Absorption; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000493:pharmacokinetics*
D054328:Proton Pump Inhibitors; D013972:Thyrotropin; D013974:Thyroxine
GI diseases; absorption; interactions; levothyroxine