Introduction
Nonarteritic anterior ischemic optic neuropathy (NAION), a rare visual disorder, has been reported in men using phosphodiesterase type 5 inhibitors (PDE5i) for erectile dysfunction.
Aim
We examined whether intermittent use of PDE5i is associated with acute NAION onset within approximately five half-lives following drug ingestion.
Methods
One hundred two ophthalmology centers in the United States and Europe identified potential cases of NAION. An expert adjudication committee conducted a blind review of the records of those with recent PDE5i use to classify cases as Definite, Possible, or not NAION. Subjects provided information on PDEi use via telephone interview. Each NAION case’s PDE5i exposure immediately prior to onset was compared against his recent patterns of use in an observational case–crossover design. A sample size of 40 cases with intermittent PDE5i exposure in the 30 days prior to NAION onset was needed to detect an odds ratio (OR) of 3.0 with 80% power.
Main Outcome Measures
The daily relative risk for acute NAION on days within five half-lives of PDE5i use vs. other days was estimated via an OR obtained from conditional logistic regression.
Results
Among 43 Definite NAION cases with PDE5i exposure in the prior 30 days, the OR was 2.15 (95% confidence interval [CI]: 1.06, 4.34). When 21 Possible NAION cases were included (n = 64), the OR was 2.36 (95% CI: 1.33, 4.19).
Conclusions
We found an approximately twofold increased risk of acute NAION within five half-lives of PDE5i use compared with use in a more prior time period. Bias from inaccurate recall of exposure was unlikely to have substantially affected the results. Based on our results, we estimate that weekly use of PDE5i adds three NAION cases per 100,000 men 50 years and older annually.
Summary
Background
Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies.
Aim
As part of a long‐term post‐marketing surveillance study requested by the US Food and Drug Administration, to compare incidence rates of gastric and other cancers after sustained exposures to pantoprazole, a long‐acting PPI, compared with other shorter acting PPIs.
Methods
We conducted a cohort study within the membership of the Kaiser Permanente Northern California healthcare system and compared rates of gastric and other cancers among pantoprazole users and users of other PPI medications. The Cox proportional hazards model was used to adjust for potential confounders such as sex, age, receipt of treatment for Helicobacter pylori, cumulative PPI dose, total years PPI treatment and year of index date. The study was developed in consultation with, and approved by, the FDA.
Results
A total of 61 684 persons with at least a 240‐day supply of medication (34 178 pantoprazole and 27 686 other PPIs) were followed up for a total of 547 020 person‐years (274 700 vs. 272 321 person‐years, respectively). The primary analyses demonstrated comparable risks between the pantoprazole and other PPI groups for gastric cancer [hazard ratio (HR) = 0.68, 95% CI 0.24–1.93); colorectal, liver, pancreatic, or small bowel cancers (HR = 0.95, 95% CI 0.65–1.40) or any cancer (HR = 1.06, 95% CI 0.93–1.21).
Conclusions
We found no evidence that pantoprazole, a longer acting PPI, compared with shorter‐acting agents, conferred an excess risk of gastric cancer, other gastrointestinal cancers or all cancers for pantoprazole compared with other shorter‐acting PPIs.
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