Investigators reported that the treatment-emergent adverse event results showed combination tamsulosin and mirabegron was well-tolerated and had a favorable safety profile.
Adding mirabegron (Myrbetriq) therapy to treat overactive bladder (OAB) symptoms in men being treated with tamsulosin (Flomax) for benign prostatic hyperplasia (BPH) is safe and well tolerated, according to results of a safety analysis published in Urology.1
OAB and BPH often occur concomitantly in men. Studies suggest about 46% of men with bladder outlet obstruction secondary to BPH have OAB, according to the authors.
Many clinicians use antimuscarinics to treat OAB, but there are concerns that the drugs may cause anticholinergic adverse effects such as dry mouth, constipation, urinary retention and potentially cognitive dysfunction. Another recommended OAB symptom treatment, the β3-adrenoceptor agonist mirabegron, appears to have a lower rate of anticholinergic adverse effects than antimuscarinic medications.
“Although the safety of mirabegron and tamsulosin as monotherapies has been comprehensively analyzed, there are a lack of clinical data on the use of the agents in combination,” the authors wrote.
The authors analyzed safety results from the phase 4, randomized, double-blind, multicenter PLUS trial (NCT02757768) that enrolled men with OAB symptoms who had been treated for BPH with tamsulosin 0.4 mg daily for 2 months or longer. The authors analyzed part of the PLUS data, including a 12-week randomized add-on treatment period with 25 mg mirabegron or placebo. Their analysis includes 352 patients taking tamsulosin plus mirabegron and 354 patients taking tamsulosin plus placebo. Most patients were 65 years and older; 1 in 8 were 75 years and older.
“The combination group demonstrated a similar safety profile to that expected for the 2 individual monotherapy components, and no new safety concerns were shown. Specifically, there was a low rate of urinary retention, and no cardiovascular concerns emerged,” said study author Sender Herschorn, BSc, MDCM, FRCSC, professor of surgery/urology at the University of Toronto, and urologist at Sunnybrook Health Sciences Centre in Ontario.
Men in the placebo group had a slightly higher frequency of treatment-emergent adverse events, at 31.4%, compared with 25.9% in the combination group. Hypertension, headache, and nasopharyngitis were the most common treatment-emergent adverse events.
Drug-related treatment-emergent adverse events were higher at 11.9% in the combination group compared with 5.9% in the placebo group. Eight men in the placebo group and 10 taking the combination experienced a serious treatment-emergent adverse event; 3 of these patients (1 taking placebo and 2 taking the combination) had serious drug-related treatment-emergency adverse events. One patient in the combination group experienced an acute myocardial infarction and cerebral infarction; 1 patient in the placebo group had angina pectoris; and 1 patient in the placebo group experienced a lacunar stroke. None of the patients died during the 12-week period. Four patients in the placebo group and 7 patients in the combination group discontinued therapy because of a treatment-emergent adverse event.
Overall, the investigators reported that the treatment-emergent adverse event results showed combination tamsulosin and mirabegron was well-tolerated and had a favorable safety profile.
This findings from this study should be viewed in combination with previously reported results from tamsulosin-plus-mirabegron studies by Kakizaki et al2 and Kaplan et al,3 Herschorn said.
“These showed efficacy for overactive bladder symptoms,” he said. “These studies provide evidence to support the use of the combination in appropriately selected men. It also provides an alternative to the combination of an alpha blocker plus an antimuscarinic in these men.”
Herschorn said the findings in this study make sense given that previous large-scale pivotal studies with mirabegron, including male subjects, have shown safety.
A limitation of the PLUS trial is that it looked at only 12 weeks of combination treatment, according to the authors.
Disclosures: Some of the authors of this study are Astellas Pharma employees. Herschorn has received grants and personal fees from Astellas Pharma; grants from Ipsen, Ixaltis, and Allergan; and personal fees from Pfizer.
1. Herschorn S, McVary KT, Santos JC, et al. Mirabegron versus placebo add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying benign prostatic hyperplasia: a safety analysis from the randomized, phase 4 PLUS study. Urology. Published online October 9, 2020. doi:10.1016/j.urology.2020.09.040
2. Kakizaki H, Lee KS, Yamamoto O, et al. Mirabegron add-on therapy to tamsulosin for the treatment of overactive bladder in men with lower urinary tract symptoms: a randomized, placebo-controlled study (MATCH). Eur Urol Focus. 2020;6(4):729-737. doi:10.1016/j.euf.2019.10.019
3. Kaplan SA, Herschorn S, McVary KT, et al. Efficacy and safety of mirabegron versus placebo add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying benign prostatic hyperplasia: a randomized, phase 4 study (PLUS). J Urol. 2020;203(6)1163-1171. doi:10.1097/JU.0000000000000738