Surprising clinical differences among alpha blockers demonstrated in post-marketing event rates

Ongoing monitoring of adverse events after medication approval can provide a real-world gauge of medication side effects in a larger, more diverse sample size. We report differences in post-marketing adverse event rates among commonly prescribed alpha blocker medications. The alpha blockers doxazosin, alfuzosin, tamsulosin, prazosin and terazosin were studied (silodosin had insufficient data). Side effect incidence was estimated by dividing the number of side effects in the Food and Drug Administration’s adverse event reporting database by the number of patients on the medication from the Medical Expenditure Panel Survey database from 2013 to 2020. Limitations of the methodology include reporting bias, an inability to verify the side effect in a patient, the lack of information on dosing, and lack of indication for which the patient was on the medication. The primary outcome was the incidence analyzed by general linear modeling with effects of adverse event type, medication, and year with multiple comparisons by Tukey’s test. Overall, doxazosin had higher incidence of side effects than alfuzosin, which in turn had higher incidence than prazosin, tamsulosin, and terazosin; the latter three were not different from one another in rates of overall side effects. Alfuzosin was more likely to cause a fall than any other alpha blocker. It is expected that doxazosin would have higher rates of vascular side effects given its selectivity profile and use as an anti-hypertensive. Alfuzosin had higher-than-expected probability of dizziness, hypotension, syncope, and dyspnea relative to the other alpha blockers (excluding doxazosin) and the highest rate of falls overall. This was unanticipated given that alfuzosin was marketed to be a somewhat uroselective medication and hence promoted as conferring fewer systemic effects.