Adverse Effects of Proton Pump Inhibitor Drugs: Clues and Conclusions

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http://www.medscape.com/viewarticle/730747_2

Abstract

Purpose of review To review evidence relating to the strength of associations

that have appeared in largely observational studies, between high-dose or

long-term use of proton pump inhibitor drugs and certain possibly attributable

side-effects, which emerge from studies confounded by other variables. In

retrospective studies not designed to assess safety, evidence of causality is

generally lacking.

Recent findings The associations of fractures of hip, wrist, forearm and other

sites appear weak and only slightly higher than the risks in control populations

matched for age. They may increase with drug exposure, but probably do so only

in individuals in whom other risk factors are also operational (smoking,

alcohol, poor nutrition, steroids, etc.). The risks of Clostridium difficile

colitis, other enteric infections, small bowel bacterial overgrowth and possibly

spontaneous bacterial peritonitis also appear increased. Impaired gastric

secretion may adversely affect the absorption of various nutrients, but their

clinical impact is ill defined. Potentially more important are the consequences

of hypergastrinemia, including rebound hypersecretion of acid, and possible

development of various cancers, including carcinoid tumors. Effects of other

drugs, including clopidogrel, on metabolism are reviewed, but clouded by

uncertainties.

Summary The safety of long-term PPI administration needs serious prospective

study.