PPI: why prescribing them outside the rules is very dangerous

"Approximately 10 percent of the general population take a proton pump inhibitor (PPI) drug to block stomach acid secretions and relieve symptoms of frequent heartburn, acid reflux and gastroesophageal reflux disease. That percentage can be as much as seven times higher for people with chronic liver disease. Researchers at University of California San Diego School of Medicine have discovered evidence in mice and humans that stomach (gastric) acid suppression alters specific gut bacteria in a way that promotes liver injury and progression of three types of chronic liver disease."

http://ucsdnews.ucsd.edu/pressrelease/common_acid_reflux_medications_promote_chronic_liver_disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388523/

Table 1.

Evidence and Clinical Recommendations for Regarding Potential Risks of PPIs.

Potential risk	Evidence	Clinical recommendation
Infections
Enteric infections	Significant evidence to suggest a twofold risk of development of Clostridium difficile-associated diarrhea with current PPI use in the community and for hospitalized patients	Weigh benefits and risks of continuation of PPI therapy in hospitalized patients
		Discontinue PPI therapy when there is no urgent indication
Community-acquired pneumonia	Minimal increase in theoretical risk, not substantiated after controlling for confounders	PPIs should not be withheld from patients with pulmonary disease
Bone fracture	Conflicting results, yet long-term use may increase risk for hip fracture	Routine guidelines for bone mineral density screening do not change with PPI therapy
		Consider long-term risks and benefits in aging patients and those at risk for osteoporosis and falls who are on long-term PPI therapy
Drug interactions
Clopidogrel	Inconsistent results across PPIs	Consider risks and benefits on individualized basis
Nutritional deficiencies
Vitamin B12	Most patients with a normal diet will not have deficiency; elderly, malnourished, and patients post-gastric bypass are at higher risk	Routine screening not recommended
		Consider screening patients at higher risk
Iron	Paucity of data to suggest direct relationship	Routine screening not recommended
		Maybe significant in patients with hemochromatosis
Magnesium	Paucity of data to suggest direct relationship	Routing screening not recommended
		Consider screening patients at higher risk, including those on additional medications that may deplete magnesium
Pregnancy	Most studies are limited to omeprazole; no significant risk of birth defects reported	Omeprazole is safe in pregnancy

Adapted from: Sheen and Triadafilopoulos [2011] and Heidelbaugh et al. [2009].

Antiplatelet interaction

"The COGENT trial, the only randomized trial to examine the possible association between clopidogrel and PPI use, randomly assigned 3873 patients with an indication for antiplatelet therapy to receive clopidogrel with omeprazole or placebo, plus aspirin [Bhatt et al. 2010]. The primary endpoint was symptomatic or occult upper GI bleeding coupled with death from cardiovascular etiologies, nonfatal myocardial infarction, revascularization, or stroke. In patients who received aspirin and clopidogrel, PPI prophylaxis exhibited a statistically significant reduction in upper GI bleeding compared with placebo (1.1% versus2.9%, respectively; HR 0.13) without increased cardiac adverse events compared with the placebo group. Since the trial was terminated prematurely, a statistically accurate assessment of cardiovascular endpoints could not be measured, yet it did not find a negative influence of PPI use on thromboembolic prophylaxis.

Based upon the data suggesting a potential adverse outcome with concomitant use of clopidogrel and PPI therapy, the US Food and Drug Administration (FDA) released a warning in November 2009 recommending avoiding concomitant use of clopidogrel with omeprazole/esomeprazole and other CYP2C19 inhibitors [FDA, 2009]. The FDA also warned that separating the administration times of clopidogrel and omeprazole did not reduce drug interaction. To date, cimetidine is the only H2RA known to interact with clopidogrel."

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