Drug Interactions with Antiulcer Agents: Considerations in the Treatment of Acid-Peptic Disease

Abstract

All of the antiulcer agents have been implicated in drug interactions. These agents generally influence the absorption, metabolism, or elimination of other medications. However, these interactions can lead to alterations in pharmacodynamic response. The mechanisms by which antiulcer agents produce drug interactions differ among the agents. It is beyond the scope of this article to review all of the drug interactions that have been reported with antiulcer agents. However, it is the intent to provide the reader with a detailed understanding of the mechanisms by which antiulcer agents may interact with other medications and to provide insight into factors that may influence the potential magnitude or clinical consequences of these interactions. An understanding of antiulcer drug interactions will aid pharmacists in assisting clinicians with drug selection and/or monitoring of drug interactions. Specifically, pharmacists can assist with the identification of potential antiulcer drug interactions and develop strategies designed to minimize adverse consequences of these interactions.

Esomeprazole induces upper gastrointestinal tract transmucosal permeability increase

“…Even given this limited permeability profile, it is possible that other (small molecule) medications a patient may be taking in addition to PPIs may have the kinetics of their appearance in the bloodstream altered by the (PPI) induction of a gastric leak pathway. It is interesting in this regard that elevation in blood digoxin levels has been reported for some time with PPI use, with one recent case study reporting digoxin elevations over 300%, resulting in hospitalization 32–34 . A similar story appears to be the case with the immunosuppressant, tacrolimus 35, 36 .…”

Pharmacologic Properties of Proton Pump Inhibitors

“…Since H 2 RAs and PPIs increase gastric pH, they can alter the absorption of drugs that are weak acids or bases, are prone to acid or alkaline degradation, or are formulated in a pHdependent controlled-release dosage form. 1,50 A high gastric pH increases absorption of digoxin, nifedipine, aspirin, midazolam, didanosine, and methadone, but the clinical significance of these effects is unclear. 50 More important, absorption of weak bases such as ketoconazole, cefpodoxime proxetil, itraconazole, and enoxacin is decreased when gastric pH is increased, which can reduce clinical efficacy.…”

“…1,50 A high gastric pH increases absorption of digoxin, nifedipine, aspirin, midazolam, didanosine, and methadone, but the clinical significance of these effects is unclear. 50 More important, absorption of weak bases such as ketoconazole, cefpodoxime proxetil, itraconazole, and enoxacin is decreased when gastric pH is increased, which can reduce clinical efficacy. These types of interactions are difficult to minimize because they reflect the pharmacologic effects of acid suppressors.…”

“…Omeprazole and esomeprazole inhibit 2C19 and interact with diazepam, phenytoin, and the R-isomer of warfarin. 1,50,51 Lansoprazole induced metabolism of CYP1A2 and led to a slight increase in metabolism of theophylline. 1 Rabeprazole and pantoprazole do not interact with the CYP system.…”

Review article: pharmacokinetic concerns in the selection of anti‐ulcer therapy

“…PPIs might alter the absorption of other drugs taken orally by significantly changing the pH of the gastric environment. Elevating the pH might affect the stability of drugs that are acid or alkaline labile and affect the absorption of drugs that have a pH‐dependent formulation 25 . Increasing the pH will decrease the dissolution of weak bases and increase the ionization of weak acids, significantly altering their rate of absorption 25 .…”