Picking a PPI: It comes down to cost
No need to be bound to the PPI you’ve always prescribed—efficacy is similar, and all have good adverse-event profiles
TABLE 3
Support vs refutation: Adverse events and long-term PPI therapy2,13-23,26,27
| POTENTIAL ADVERSE EVENT | PROPOSED MECHANISM | SUPPORT OR REFUTATION |
|---|---|---|
| Elevated serum gastrin levels and increased enterochromaffin-like (ECL) cells | PPIs elevate serum gastrin levels by interfering with negative feedback mechanism on gastrin release | Gastrin levels can be increased but typically remain within the normal range.2 Due to potential for gastrin to affect growth of tumors outside the gastrointestinal tract, further study of a potential relationship with stimulating tumor growth is needed.13 An increase in ECL cells has been seen in humans; neoplastic findings have not been seen in humans.2,13-15 |
| Vitamin B12 deficiency | Vitamin B12 depends on gastric acid to be released and absorbed from food. In the absence of gastric acid, there is potential for deficiency16 | There is no association between chronic PPI therapy and substantial reduction of vitamin B12.16 Consideration should be given to monitoring vitamin B12 levels periodically in patients who may be at higher risk for vitamin B12 deficiency.13 A small case-control study showed an association between vitamin B12deficiency and PPI/H2 antagonist therapy (OR=4.45, 95% CI 1.47-13.34). Other causes were not explored and data were not separated from the H2 antagonist group.16 |
| Risk of hip fracture | PPIs may inhibit bone resorption and reduce calcium absorption by inducing hypochlorhydria17 | In 2006, a nested, observational case-control study associating high-dose chronic PPI use with a higher incidence of hip fractures showed an adjusted OR=1.44 (95% CI 1.30-1.59) in patients on PPI therapy > 1 year.17 |
| Risk of community-acquired pneumonia (CAP) | Prolonged hypochlorhydria could lead to bacterial overgrowth | A case-control study had an adjusted OR=1.5 (95% CI 1.3-1.7) and the strongest association (OR=5; 95% CI 2.1-11.7) between PPI use and CAP was in patients who had started a PPI within the past 7 days.18 A higher percentage of case patients were on corticosteroid therapy and had concurrent chronic obstructive lung disease, diabetes mellitus, and heart disease. A small study of critically ill trauma patients did not find an increased risk of nosocomial infections in patients taking PPIs.19 A pediatric prospective study found 2 cases of pneumonia in follow-up of the control group of 95 patients, and 11 cases of pneumonia in 91 patients in the combined gastric acid suppression group (P=0.03).20 This trial did not differentiate between ranitidine and omeprazole and excluded patients with diseases identified as confounding variables in previous studies. |
| Risk of Clostridium difficile infection | Prolonged hypochlorhydria could lead to bacterial overgrowth | A case-control study found that the OR for a PPI exposure within the past 3 months and C difficile infection was 3.5 (95% CI 2.3-5.2).21 Previous antibiotic exposure within the same period was associated with an OR of 8.2 (95% CI 6.1-11.0). Notably, in this study, inflammatory bowel disease, renal failure, MRSA, cancer, pernicious anemia, and recent antibiotic use were all associated with a higher adjusted OR for increased risk of C difficile infection than PPI exposure. A 2nd cohort study found an unadjusted OR of 3.1 (95% CI 1.7-5.6) for PPIs and C difficile infection. Of note, higher unadjusted ORs were seen with both renal failure and MRSA.22 Another case-control study did not establish an association between PPI use and C difficile hospitalizations.23 |
| Atrophic gastritis | Unknown | One cohort study found atrophic gastritis can occur with chronic omeprazole therapy,26 but it should be noted that of 20 who patients developed atrophy, 18 were infected with H pylori (P < 0.001) and 2 were not infected (P=0.62). In a separate study, omeprazole was not associated with gastric atrophy after 3 years.27 |
Drug interactions
Two main types of drug interactions may occur with PPIs: those at the cytochrome P450 level, and those due to decreased absorption caused by acid suppression.
PPIs are metabolized by both CYP 2C19 and CYP 3A4. Theoretically, any medication that can induce or inhibit either of these enzymes could affect PPI blood concentration levels.
Evidence suggests omeprazole and its enantiomer esomeprazole have the most potential of the PPIs for drug interactions, as they have been shown to increase blood concentration levels of phenytoin, benzodiazepines, carbamazepine, cilostazol, clarithomycin, and R-warfarin by inhibiting CYP 2C19.2,3,29 These interactions do not typically require a dose adjustment. However, more frequent monitoring may be appropriate.2,6
As a class, PPIs may decrease or increase the bioavailability of drugs whose absorption is dependent on gastric pH. Common medications that are pH dependent for absorption are the azole antifungals, ampicillin, cefpodoxime, indinavir, delavirdine, cyanocobalamin, iron, and digoxin.2,3,6 Digoxin absorption may be increased, resulting in elevated digoxin levels. Enteric-coated medications, which typically dissolve at a higher pH, may also be affected by PPI therapy.2
There may be a decrease in PPI efficacy if given concurrently with other antisecretory medications such as histamine 2 (H2) antagonists or misoprostol. This interaction is apparently due to the capability of PPIs to exert their effects only on actively secreting proton pumps.2,29
