Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide. In recent years, there has been a marked increase in prescribing PPIs coinciding with reductions in cost due to patent expiry and generic formulations. What are the unintended consequences of this addiction and what practical approaches are there to control?
Risks, pathogenesis and practice
This recent Medical Journal of Australia piece examined risks of PPI administration and various gastrointestinal and non-gastrointestinal diseases. One of the more pertinent findings was a meta-analysis of observational studies reporting significant risks of Clostridium difficile-associated diarrhoea and other enteric infections, including Salmonella and Campylobacter species in patients receiving a PPI. While observational studies do not account for detection bias and confounding, the observed association should not be ignored.
Changes in local bacterial diversity, presumably resulting from PPI-induced alterations to intestinal lumen pH, are thought to underlie the increased risk of developing GI infection. The association of PPI administration with increased C. difficile risk raises the (controversial) possibility that vegetative forms rather than spores of C. difficile are primarily responsible for transmission ( if spores were dominant then a PPI effect should not be observed). [There is a discussion of the evidence within this 2011 position statement on C. difficile control – see the hand hygiene section].
A recent investigation into PPI prescribing patterns in the UK found that 60% of primary care physicians made no attempt to reduce patients’ doses over time, and almost 50% of patients receiving long term PPI therapy had no clear indication for its continuation. The situation in Australia and New Zealand is likely to be similar.
Also of note, if PPI overuse leads to an excess of bacterial GI infections, that in turn may increase prescription of quinolones and other agents which are known risk factors per se for C. difficile infection. A perfect storm!
Embedding PPI Stewardship within AMS programs
Given significant risks of chronic administration, ongoing PPI prescription requires a clear indication and regular prescription review is indicated to identify opportunities for de-prescribing.
NPSMedicineWise has a great overview on acid-peptic disorders and appropriate short term PPI therapy strategies.
In particular, we recommend this useful deprescribing algorithm from Primary Health Tasmania:
A good example of a coupled AMS+PPI approach comes from this prospective audit and feedback study that looked to reduce the co-administration of antibiotics and PPIs among hospitalized patients due to their association with C. difficile infection. Simple “piggy-backing” strategies such as these could potentially increase the effectiveness of AMS strategies.
- Tenni, Peter, Dunbabin, David. A guide to deprescribing proton pump inhibitors. Primary Health Tasmania, accessed 28 October 2016
- Campylobacter enteritis [revised 2014 Nov]. In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; 2015 Jul.
- Gracie, David J., and Alexander C. Ford. “The possible risks of proton pump inhibitors.” Med J Aust 205, no. 7 (2016): 292-293.
- Kandel, Christopher E., Suzanne Gill, Janine McCready, John Matelski, and Jeff E. Powis. Reducing co-administration of proton pump inhibitors and antibiotics using a computerized order entry alert and prospective audit and feedback. BMC Infectious Diseases 16, no. 1 (2016): 355.
- Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol 2007; 102: 2047-2056.
- NPS Medicinsewise 2016, Proton Pump Inhibitor (PPI) Dosage and Administration, NPS, accessed 28 October 2016.
- Othman F, Card TR, Crooks CJ. Proton pump inhibitor prescribing patterns in the UK: a primary care database study. Pharmacoepidemiol Drug Saf 2016; doi: 10.1002/pds.4043