Post marketing surveillance is a critical component of evaluating medication safety profiles. Ongoing monitoring of medication adverse events after medication approval can often provide a better gauge of adverse events utilizing a larger, more diverse sample size. These strategies can investigate if certain medications have higher rates of adverse events or reveal if there is a particularly concerning adverse event compared to other medications in their class. We sought to understand differences in adverse event rates among medications in the alpha blocker class to better assess each individual medication’s safety profile.

The alpha blockers studied were doxazosin, alfuzosin, tamsulosin, prazosin and terazosin. We utilized publicly available data from the Medical Expenditure Panel Survey maintained by the Agency for Healthcare Research and Quality in the United States. This data set enables recording the total number of patients on each medication in the alpha one inhibitor class as a proxy for the denominator. The Food and Drug Administration’s adverse event reporting database (FAERS) was accessed in order to determine the total number of adverse events reported per year per medication as a proxy for the numerator. Date ranges of 2013 to 2020 were utilized for both databases.  The primary outcome was the reported incidence of a side effect per 100,000 medication users. A general linear model was used to assess the incidence as a function of drug, type of side effect, and an interaction between drug and side effect. Tukey’s test was used for multiple comparisons. We reported the percentages of each side effect for each alpha blocker for the package insert and for the incidence of reported FAERS adverse events. This was followed by a relative percent and incidence, respectively using doxazosin as the reference number 1.

Results are reported in Figure 1 and Table 1. The following were all statistically significant. There was a main effect of drug with doxazosin having a higher incidence than alfuzosin which in turn had a higher incidence than prazosin, tamsulosin, and terazosin; these latter three were not different from one another.  In order of occurrence side effects were hypotension, dizziness, syncope, fall, dyspnea, orthostatic hypotension, and headache. In addition, there was a significant relationship between particular medications and the incidences of specific side effects. Alfuzosin was more likely to cause a fall than doxazosin but for almost all other side effects doxazosin caused more than alfuzosin.

It is expected that doxazosin would have higher rates of vascular side effects given its selectivity, clinical use as an anti-hypertensive, and the predictions from the package inserts. Doxazosin had higher rates of headache, dizziness, syncope and dyspnea.  Alfuzosin had higher than expected probability of dizziness, hypotension, syncope, dyspnea, and falls than expected relative to the other alpha blockers based on the package insert, excluding doxazosin. Tamsulosin and terazosin had lower than expected relative probability for the same events. This was unanticipated given that alfuzosin was marketed to be a uroselective medication and hence promoted as having less of a systemic effect.

Post-market surveillance data suggests markedly different relative side effect rates among alpha blocker medications than is found in the published package inserts. These findings may encourage a change in the utilization of specific alpha blocker medications in patients with varying risk profiles or experiencing specific side effects. This study may contribute to the understanding of how different medications in this class compare to one another on side effect profile post-approval. Also, this study may contribute new information on how these medications compare in overall fall rates in the population.  Limitations of our study include post-marketing incidence of side effects may be significantly underreported; this discrepancy between real-world and reported data may obfuscate the relationships shown between package insert percentages and post-marketing incidence. Additionally, the doses of each alpha-blocker were unknown relative to the side effect incidences.

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