Background: Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain.
Objectives: The present case-control study employed 2 million longitudinal claims in 2011-2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA).
Methods: The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice.
Results: Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94-2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73-2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94-3.70, P < 0.05).
Conclusions: This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.
Keywords: anaemia; drug interaction; gastric acid; histamine H2 antagonist; iron; proton pump inhibitor.
Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists, 2 kinds of gastric suppressants commonly used for gastroesophageal reflux disease, decrease iron absorption in the gut and thus increase the risk of developing iron-deficiency anaemia (IDA). We constructed a retrospective matched case-control study within the Taiwan National Health Insurance Research Database. The longer period of PPIs/H2 antagonists used, the higher risk of IDA was, with the highest risk in female elderly groups (adjusted odds ratio = 2.68 in females aged ≥ 50). PPI users had a higher risk than H2 antagonist users during the 1-year follow-up. The prescription patterns postdiagnosis of IDA witnessed considerable drops for both groups, with less than a 10th of original users remaining the usages (1.72% and 9.85% taking PPIs and H2 antagonists within 90 days after receiving a diagnosis, respectively). Physicians and pharmacists should be aware of the risk of developing IDA in patients currently undergoing or expected to take long-term gastric acid suppressants.
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