Recent Safety Concerns With Proton Pump Inhibitors

Abstract

There have been recent concerns about the safety of proton pump inhibitors (PPIs). We focus here on 3 specific concerns-the possible interaction between PPIs and clopidogrel, the postulated link between PPI use and fractures, and the possibility that long-term PPI use might lead to hypomagnesemia. There is evidence for an in vitro interaction between clopidogrel and at least some PPIs. The Food and Drug Administration (FDA) has warned against the use of certain PPIs by patients on clopidogrel. However, a randomized controlled trial that compared clopidogrel alone with the combination of clopidogrel and omeprazole found no increase in adverse cardiovascular outcomes and a reduction in the rate of adverse gastrointestinal outcomes attributable to omeprazole. PPI use may be a weak risk factor for certain fractures, but the quality of evidence is relatively poor and there is a strong possibility of confounding. The mechanism whereby PPI use might increase fracture risk is unknown. Currently, no additional measures concerning calcium supplementation or bone mineral density monitoring are recommended for patients on a PPI. The FDA has suggested monitoring serum magnesium levels in patients on PPI therapy. The mechanism and frequency of PPI-induced hypomagnesemia are unclear. PPI treatment should not be withheld from patients who genuinely require it, but the PPI should be taken in the lowest effective dose and only for as long as clinically indicated. The same is, of course, true for all medicines. The benefits of PPI therapy greatly outweigh the risks.

Proton pump inhibitor prescribing patterns in the UK: a primary care database study

“…As PPIs have become commonly 29 used for long-term maintenance, concerns have been raised about the safety of such use 6 . 30 Studies have showed that PPI use is associated with malabsorption of vitamins and 31 minerals 7,8 , an increased risk of infections, such as pneumonia 9 and enteric infection 10 , and 32 an increased fracture risk 11,12 .…”

“…The importance of reducing any overuse of PPIs is not limited to the associated costs, but 28 also to the risks of taking the drugs on a long-term basis 6 . As PPIs have become commonly 29 used for long-term maintenance, concerns have been raised about the safety of such use 6 .…”

A Drug Utilization Study of Cognition Enhancers in Dementia in a Tertiary Care Hospital in Mumbai

“…Antacids may affect the absorption of other medications and should not be prescribed in individuals with decreased renal function due to the risk of accumulation of aluminum and magnesium [26]. Long term Proton pump inhibitor therapy should also be avoided as, according to recent reports, they are known to cause osteoporosis, vitamin B 12 deficiency, interact with clopidogrel among other effects [27][28][29].…”

PPI co‐therapy did not adversely affect outcomes in clopidogrel users

“…Their main finding -that PPI co-therapy did not modify the protective effect of clopidogrel -is in keeping with our recent analyses of the literature. 2,3 Hopefully, their findings will go some way towards resolving the ongoing controversy about the use of PPIs by patients on clopidogrel.…”