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drug adverse effects of proton pump inhibitors (PPI)

Adverse effects: 1) most common a) headache, diarrhea, abdominal pain, constipation b) switching to another PPI is generally sufficient to reduce or eliminate the adverse effect(s) [22] 2) increased risk of C difficile colitis [1,10,19,21,39] RR=1.7 3) increased risk of community-acquired pneumonia (0.05%) [2] a) especially recent initiation of use [4] b) risk* may be greater for - elderly - COPD - asthma - immunocompromised c) not associated with increased risk of community-acquired pneumonia [36] 4) increased risk of nosocomial pneumonia (HR=2.5) [7,8,17] - increased risk of nosocomial pneumonia in stroke patients [27] 5) increased risk of serious infection, including severe or fatal COVID-19 (RR=1.46) [57], hepatic encephalopathy & bacterial peritonitis in cirrhotic patients with ascites [6,35] - H2 receptor antagonists apparently safe [6] 6) increased risk for multidrug-resistant organisms [56] 7) increased risk of fracture: [3,12,20,23] - fracture risk increased at higher PPI doses & for duration of therapy > 1 year [22] - association with risk of hip fracture is inconsistent [22] - not associated with increased risk of hip fracture [50] - wrist fracture, vertebral fracture [3,23] - not associated with changes in bone mineral density [37] 8) no increase in risk of colorectal cancer [5] 9) rebound gastric hyperacidity may occur in patients when proton pump inhibitor is stopped after 1-2 months of use; best managed with antacids [9,15] 10) risk of birth defects a) within 1st 4 weeks prior to conception (HR 1.39); risk lowest for omeprazole b) not associated with when taken by pregnant women during 1st trimester [16] 11) hypomagnesemia [18,22] 12) acute interstitial nephritis [22,26,31] (hypersensitivity) 13) increased risk for chronic renal failure (14.2 vs 10.7 per 1000 person-years, RR=1.3) [29] - number needed to harm: 286 for 1 year to cause 1 case of chronic renal failure - RR=1.3 for 2-fold increase in serum creatinine or 30% decrease in eGFR [41] - 0.5% excess absolute risk for >50% reduction in GFR within 5 years [43] 14) 2-fold increase in cardiovascular mortality with PPI use - increased risk in MI (RR=1.16) [28] - no increased risk in MI [47] - H2-blockers not associated with increased risk - increased risk of stroke within 180 days of initiation of PPI therapy (RR=1.28, RR=1.77 within 30 days) [40] - not associated with increased risk of stroke [48] - increase risk of all-cause mortality relative to use of H2-blockers or no acid suppression (RR=1.25) [42] - excess mortality from CV disease & chronic kidney disease [53] 15) increased risk of dementia in the elderly (RR=1.44) [30] - increased risk for dementia (RR=1.85) [61] - longer use of PPI associated with inncreased risk for dementia [62] - no increased risk for Alzheimer's disease [44] - PPI use associated with diminished risk of cognitive impairment [45] - no increased risk of dementia [49,55] 16) increased risk of fundic gland polyps (RR=2.46) [34] 17) increased risk of gastric cancer - 2-fold independent of prior H pylori infection [46] - RR=1.45, number needed to harm 2100 in 5 years [58] 18) increased risk of iron-deficiency anemia (RR=2.5) [38] 19) increased risk of vitamin B12 deficiency [22] 20) long-term use of PPIs is associated with increased risk of type 2 diabetes [60] 21) long-term use of PPIs is associated with increased risk of NAFLD non-alcoholic fatty liver disease (RR=2.0 for use > 5 years) [59] 22) use during the 1st 6 months of life associated with increased risk for food allergy during childhood (RR=2.6) [51] 23] increased risk for allergy * Low pH of stomach acid is antimicrobial. In the absence of acid, refluxed & aspirated gastric contents may contain pathogen that causes pneumonia. * pharmacy guidelines require reassessment of need after 8 weeks of therapy

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DRUGS: proton pump inhibitor FORM: drug adverse effects proton pump inhibitor

References

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