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The impact of proton pump inhibitors on levothyroxine absorption: The good, the bad and the ugly

Published:February 21, 2020DOI:https://doi.org/10.1016/j.ejim.2020.02.020
      Levothyroxine (LT4) and proton pump inhibitors (PPI) are two of the most prescribed drugs particularly in elderly population [
      • Skelin M.
      • Lucijanić T.
      • Klarić D.A.
      • Rešić A.
      • Bakula M.
      • Liberati-Čizmek A.M.
      • et al.
      Factors affecting gastrointestinal absorption of levothyroxine: a review.
      ,
      • Benvenga S.
      • Pantano R.
      • Saraceno G.
      • Lipari L.
      • Alibrando A.
      • Inferrera S.
      • et al.
      A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences.
      ]. As they are frequently co-ingested, the effect on levothyroxine absorption is especially relevant due to its narrow therapeutic index [
      • Skelin M.
      • Lucijanić T.
      • Klarić D.A.
      • Rešić A.
      • Bakula M.
      • Liberati-Čizmek A.M.
      • et al.
      Factors affecting gastrointestinal absorption of levothyroxine: a review.
      ]. It is well established that an acid gastric pH is required to the dissolution of LT4 before its absorption in the intestine. Accordingly, some in vitro studies illustrated that an increase in the gastric pH affects the dissolution of the LT4 tablet [
      • Vita R.
      • Fallahi P.
      • Antonelli A.
      • Benvenga S.
      The administration of l-thyroxine as soft gel capsule or liquid solution.
      ]. As PPI act by blocking the secretion of gastric acid through covalent binding to the H+/K+ATPase enzyme they have been included in the list of factors affecting gastrointestinal absorption of levothyroxine with moderate clinical significance [
      • Skelin M.
      • Lucijanić T.
      • Klarić D.A.
      • Rešić A.
      • Bakula M.
      • Liberati-Čizmek A.M.
      • et al.
      Factors affecting gastrointestinal absorption of levothyroxine: a review.
      ]. Regarding the appropriate timing of LT4 administration it has been widely recommended for tablets to be taken during fasting before breakfast [
      • Vita G.
      • Saraceno F.
      • Trimarchi S.
      • Benvenga S
      Switching levothyroxine from the tablet to the oral solution formulation corrects the impaired absorption of levothyroxine induced by proton-pump inhibitors.
      ]. Similarly, PPI are usually ingested during the morning before breakfast and that is one of the main reasons because the co-ingestion of these two drugs is a matter of concern particularly for the clinicians who prescribed and follow-up the patients due to the impact that PPI may have on LT4 treatment.
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