BACKGROUND:Type 1a selective alpha-blockers (referred to as T1a), used in treatment of benign prostatic hyperplasia (BPH), are also used off-label to improve stone passage rates in nephrolithiasis. However, little is known about its relative safety in nephrolithiasis compared to BPH. We sought to examine the rate of adverse T1a reactions (dizziness, fainting, hypotension) in male patients with nephrolithiasis in a contemporary real-world dataset, with indication of BPH serving as a comparator. We also hypothesized that old age would be associated with greater target side effects.
METHODS:A pharmacovigilance case-noncase study using disproportionality analysis was conducted to detect signals of adverse drug reactions of interest associated with usage of T1a blockers (tamsulosin, silodosin) for nephrolithiasis. Data was collected from VigiBase. All other adverse events reported in Vigibase were used as a control group. Signal detection and strength was assessed using the reporting odds ratio (ROR) and its 95% confidence interval (CI). Subgroup analyses were performed, stratifying by age (<65 and ≥65 years).
RESULTS:We identified 459,446 reports of target side effects in men, of which 3449 (0.75%) were reported with T1a blockers. T1a blockers were associated with more target side effects (ROR 1.61; 95% CI 1.55-1.66). Taking T1a blockers for nephrolithiasis was associated with higher risk compared to BPH (ROR 1.98; 95% CI 1.25-3.13), and this was not due to risk differences between nephrolithiasis and BPH, as the former was significantly associated with fewer side effects (ROR, 0.68; 95% CI, 0.53-0.86). In older patients, taking T1a blockers for nephrolithiasis was also associated with increased risk of side effects compared to BPH (ROR 4.73; 95% CI 2.26-8.46), and this was likewise not due to risk differences between nephrolithiasis and BPH. In patients taking T1a blockers for nephrolithiasis, old age significantly increased risk of having target side effects (ROR, 3.44; 95% CI, 1.32-8.95)
CONCLUSIONS:Our analysis shows that in all male patients, use of T1a blockers for nephrolithiasis is associated with higher risk of dizziness, falling, and hypotension compared to BPH, despite nephrolithiasis naturally being associated with equal or fewer target side effects. Furthermore, we found that older men are at particularly increased risk of target side effects. We reason that this higher risk may be due to the acuity of T1a blocker usage in these patients, which may often be associated with pain, use of other medications, dehydration, poor diet, and overall sickness and might predispose to adverse T1a reactions. While there is possible confounding by these unmeasured factors, our results support the need of continued monitoring of off-label T1a blocker use in all male patients with nephrolithiasis.
