Physicians should exercise vigilance when prescribing PPIs for more than one year, warn researchers from Melbourne who found a clear association between iron deficiency and PPI use in terms of duration of treatment and dosage.

According to the authors led by Dr An Duy Tran, a Senior Research Fellow at the Melbourne School of Population and Global Health, the findings suggest that although not endorsed by current guidelines, physicians should consider routine monitoring of haemoglobin levels in patients on long-term PPI therapy who have symptoms of iron deficiency.

“Physicians should also check if patients with iron deficiency are receiving PPIs so that appropriate measures to minimise the consequences of iron deficiency can be determined,” they advised in their paper published in the Journal of Internal Medicine.  

In the case-controlled study involving more than 50,000 patients the adjusted Odds Ratios (ORs) for iron deficiency in “full” PPI users (continuous PPI therapy for at least one year) compared to people who had not received PPIs was 3.60 [95% CI 3.32-3.91]. In limited users this figure was 1.51 (95% CI 1.44-1.58]. Compared to limited users the adjust OR in “full” PPI users was 2.39 {95% CI 2.19-2.60].

A relationship was also seen between the dose of PPI and the risk of iron deficiency, with  people using one tablet of 20 mg PPI or more daily at a higher risk of iron deficiency compared with people using less than one tablet daily.

The research team noted that there was increasing evidence of adverse events associated with long-term PPI use, such as hypomagnesemia, enteric infections, cobalamin deficiency, chronic kidney disease, fundic gland polyps and gastric cancer.

“Therefore, it is crucial to increase vigilance when prescribing PPIs and adhere to existing guidelines,” they concluded.