Passing Stones With PDE5 Inhibitors

Selezionata da Pietro Cazzola

Kidney stonesNow that we have made the most likely diagnosis of a kidney stone, we can potentially avoid a urologic procedure if we expel it. Of the 22% of kidney stones that wind up in the ureter, two-thirds will be lodged in the distal ureter.
Tamsulosin works, and prednisolone may also be helpful. Anything else?

Dr. Kumar Jayant of Sudha Hospital and Medical Research Center, Kota, India, and associates investigated the efficacy of a phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) to facilitate kidney stone expulsion. PDE5 inhibitors increase levels of cyclic guanosine monophosphate and cause ureteric relaxation (Int. J. Urol. 2014 June 3 [doi:10.1111/iju.12496]).
In this study, 244 patients with distal ureteral stones between 5 and 10 mm (about a 50% chance of passing) quantitated with noncontrast CT were randomized to two groups: tamsulosin (0.4 mg daily) or tamsulosin (0.4 mg daily) plus tadalafil (10 mg daily). Medications were given for 4 weeks.
The average patient age was about 37 years, and the mean stone size was 7 mm. Participants were included only if their pain was relieved within a day by diclofenac injection. Potential participants were excluded if they had fever, hydronephrosis, multiple kidney stones, a history of surgery or endoscopic procedures, or diabetes; were taking calcium channel blockers or nitrates; were pregnant or lactating; or required immediate treatment. If stones were not passed in 4 weeks, ureterorenoscopy was used to remove them.

The tamsulosin/tadalafil combination was associated with a statistically significantly higher rate of expulsion (83.6% vs. 65.5%; P = .031) and a shorter time to expulsion (14.9 days vs. 16.7 days; P =.003). Tamsulosin/tadalafil was associated with significantly fewer hospital visits and less need for pain medications. Not surprisingly, tamsulosin/tadalafil improved erectile function. However, patients taking the tamsulosin/tadalafil combination also had more headaches, dizziness, orthostatic hypotension, and backaches.
In certain patients, hypotension may be a concern with this combination. However, the researchers highlighted a study whose authors concluded, “in subjects on tamsulosin, tadalafil 10 and 20 mg produced mean maximal decreases in standing [systolic blood pressure] that were similar to placebo” (J. Urol. 2004;172(5, pt. 1):1935-40).
Out-of-pocket cost may be a barrier for some patients. But given the significance of these findings (an almost 20% difference in expulsion rate), total cost of care may be significantly reduced for these patients.

Dr. Jon O. Ebbert