The rates of common adverse events reported during treatment with proton pump inhibitors used in general practice in England: cohort studies.
OBJECTIVE
To estimate the rates of common adverse events in patients treated with the proton pump inhibitors omeprazole, lansoprazole and pantoprazole in general practice in England.


METHODS
In prescription-event monitoring cohort studies, data on dispensed prescriptions prescribed by general practitioners in England soon after each drug was launched were linked to subsequent clinical events recorded by the prescriber. 16 205 patients prescribed omeprazole between June 1989 and June 1990, 17 329 patients prescribed lansoprazole between May and November 1994, and 11 541 patients prescribed pantoprazole between December 1996 and June 1997 were studied.


RESULTS
The commonest adverse events in the omeprazole, lansoprazole and pantoprazole cohorts were diarrhoea (incidence: 0. 18, 0.39 and 0.23 per 1000 days of exposure, respectively); nausea/vomiting (incidence: 0.16, 0.22 and 0.18 per 1000 days of exposure, respectively); abdominal pain (incidence: 0.17, 0.21 and 0. 17 per 1000 days of exposure, respectively); and headache (incidence rates: 0.10, 0.17 and 0.15 per 1000 days of exposure, respectively). The remaining adverse events occurred at rates of less than 0.11 per 1000 days of exposure. There were little absolute differences in the rates of most events between the three proton pump inhibitors. However, diarrhoea was more commonly associated with lansoprazole compared with omeprazole (rate difference: 0.21 per 1000 days of exposure; 95% CI 0.17, 0.25; rate ratio: 2.11; 1.78, 2.51), and there was a clear age-response relationship.


CONCLUSIONS
Adverse events occurred relatively infrequently in all three cohorts. There were only small absolute differences in event rates between the three drugs, although these data suggest the hypothesis that lansoprazole is associated with more frequent occurrence of diarrhoea, particularly in the elderly.
Martin
R M
RM
University of Bristol, Department of Social Medicine, Canynge Hall, Whiteladies Road, Bristol, UK. richard.martin@bristol.ac.uk
Dunn
N R
NR
Freemantle
S
S
Shakir
S
S
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D001562:Benzimidazoles / Q000009:adverse effects; D015331:Cohort Studies; D003967:Diarrhea / Q000139:chemically induced; D011307:Drug Prescriptions; D004739:England; D005194:Family Practice; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000009:adverse effects
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D000077402:Pantoprazole; D009853:Omeprazole