PROTON-PUMP INHIBITORS

 
Drug Duodenal Ulcer Gastric Ulcer H. pylori tx GERD
Omeprazole (Prilosec) 20mg QD x 4wks 20-40mg QD x 4-8wks 20mg QD 20-60mg QD
Esomeprazole* (Nexium)       20-40mg QD
Lansoprazole (Prevacid) 15mg QD x 4wks 30mg QD x 4-8wks 30mg QD 15-30mg QD
Rabeprazole (Aciphex) 20mg QD x 4wks 20-40mg QD x 4-8wks 20mg QD  
Pantoprazole (Protonix)       40mg QD

*--Esomeprazole is the s-isomer of omeprazole

  1. Pharmacology
    1. Reduce HCl secretion more than H2-blockers
    2. Omeprazole inhibits cytochrome p-450 enzymes (see above under "Cimetidine")
  2. Adverse effects
    1. Can cause some nausea, abd. pain, constipation or diarrhea; acute interstitial nephritis has been reported
    2. May increase risk of pneumonia
      1. In a prospective study of a population of 364,000 pts over 3y, use of either H2-blockers or PPIs were ass'd with RR 4.5 for incidence of community-acquired pneumonia (JAMA 292:1955, 2004--JW)
      2. In a prospective cohort study in 63,878 pts > 18yo hospitalized for 3 or more days, those who received orders for H2-blockers or PPIs had sig. higher incidence of hospital-acquired pneumonia (OR 1.3 after adjustment for potential confounders); in subgroup analyses, use of PPIs was associated with sig. elevated risk (OR 1.3) but use of H2-blockers was not (JAMA 301:2120, 2009-abst)
    3. Cause hyperplasia of gastric enterochromaffin-like cells in animals & humans and neuroendocrine cell tumors and hepatocellular carcinoma in animals
    4. May accelerate the progression of Osteoporosis by interfering with calcium absorption
      1. In a retrospective study of about 400,000 pts who received at least one prescription for a PPI and/or H2 blocker, after adjustment for potential confounders, pts on a PPI for > 1y had sig. increased incidence of hip fracture (RR 1.44) c/w pts who did not use any acid-suppression therapy. No sig. diff. between users of H2 blockers and non-users. There was evidence of a dose- and duration-dependent effect (JAMA 296:2947, 2006--JW)
      2. In a cross-sectional populationg study, PPI use, after controlling for potential confounders, was not sig. associated with risk of osteoporosis (Gastroent. 130:896, 2010-JW)
      3. In a study using data from the Women's Health Initiative on 161,806 women 50-79yo overmean 7.8y f/u, after adjustment for potential confounders, there was no sig. diff. in risk of hip fx or mean change in BMD in PPI users vs. non-users, but PPI use was associated with sig. increase in risk of clinical spine fx (HR 1.47) and forearm or wrist fx (HR 1.26) (Arch. Int. Med 170:765, 2010-AFP 6/1/2010)
      4. In an analysis of data form the Nurses' Health Study, among 80,000 women, after adjustment for potential confouners, risk for hip fracture was sig. higher (RR 1.4) among women who used PPIs regularly for 2y or more; increased duration was associated with increased risk.  In subgroup analysis, the increased risk with PPI use was seen only in women with history of smoking and not in those who had never smoked.  (BMJ 344:e372, 2012-JW)
    5. Some evidence for rare association with Acute Interstitial Nephritis in children from retrospective studies (Clin. Gastroent. Hepatol. 4:597, 2006--JW)
    6. Some association with risk of Clostridium dificile colitis
    7. Long-term use may be associated with hypomagnesemia
    8. May interfere with efficacy of antiplatelets including Clopidogrel
  3. See section on NSAIDs for info on use of PPI's for prevention of NSAID-induced ulcers