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Ito H, Negoro H, Kono J, Hayata N, Miura T, Manabe Y, Miyazaki Y, Mishina M, Woo JT, Sakane N, Okuno H. Effectiveness and Safety of a Mixture of Nobiletin and Tangeretin in Nocturia Patients: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study. J Clin Med 2023; 12:2757. [PMID: 37109094 PMCID: PMC10143228 DOI: 10.3390/jcm12082757] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 03/29/2023] [Accepted: 04/03/2023] [Indexed: 04/29/2023] Open
Abstract
Nobiletin and tangeretin (NoT) are flavonoids derived from the peel of Citrus depressa, and they have been found to modulate circadian rhythms. Because nocturia can be considered a circadian rhythm disorder, we investigated the efficacy of NoT for treating nocturia. A randomized, placebo-controlled, double-blind, crossover study was conducted. The trial was registered with the Japan Registry of Clinical Trials (jRCTs051180071). Nocturia patients aged ≥50 years who presented nocturia more than 2 times on a frequency-volume chart were recruited. Participants received NoT or a placebo (50 mg once daily for 6 weeks), followed by a washout period of ≥2 weeks. The placebo and NoT conditions were then switched. Changes in nocturnal bladder capacity (NBC) were the primary endpoint, and changes in nighttime frequency and nocturnal polyuria index (NPi) were secondary endpoints. Forty patients (13 women) with an average age of 73.5 years were recruited for the study. Thirty-six completed the study, while four withdrew. No adverse events directly related to NoT were observed. NoT had little effect on NBC compared with the placebo. In contrast, NoT significantly changed nighttime frequency by -0.5 voids compared with the placebo (p = 0.040). The change in NPi from baseline to the end of NoT was significant (-2.8%, p = 0.048). In conclusion, NoT showed little change in NBC but resulted in decreased nighttime frequency with a tendency toward reduced NPi.
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Affiliation(s)
- Haruki Ito
- Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Hiromitsu Negoro
- Department of Urology, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
| | - Jin Kono
- Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Naoki Hayata
- Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Takayoshi Miura
- Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Yumi Manabe
- Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Yu Miyazaki
- Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Mutsuki Mishina
- Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Je Tae Woo
- Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, Kasugai 487-8501, Japan
| | - Naoki Sakane
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Hiroshi Okuno
- Department of Urology, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
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吉田 正. [Management for lower urinary tract dysfunction in the elderly according to guidelines]. Nihon Ronen Igakkai Zasshi 2022; 59:115-130. [PMID: 35650043 DOI: 10.3143/geriatrics.59.115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Chen Q, Mao Y, Zhou H, Tang S. Discontinuation Rates of Tadalafil Alone and in Combination with a-Blockers in the Treatment of Male Lower Urinary Tract Symptoms with or without Coexisting Erectile Dysfunction: A Systematic Review and Meta-Analysis. Int J Clin Pract 2022; 2022:9298483. [PMID: 36419863 PMCID: PMC9649306 DOI: 10.1155/2022/9298483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 10/12/2022] [Accepted: 10/15/2022] [Indexed: 11/06/2022] Open
Abstract
PURPOSE We examined the discontinuation rates of tadalafil alone and in combination with a-blockers (ABs) for the treatment of male lower urinary tract symptoms (LUTS), with or without erectile dysfunction (ED). MATERIALS AND METHODS We searched the EMBASE, PubMed, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases for studies published until May 15, 2022. The discontinuation rates associated with LUTS medications were subsequently analyzed by meta-analysis. RESULTS Forty-four studies, including 1724 discontinued patients, were included. The combined discontinuation rate was 12.78% (95% confidence interval (CI) 9.89-15.98%), and the discontinuation rates because of adverse events and lack of efficacy were 4.56% (95% CI 3.39-5.90%) and 3.30% (95% CI 1.53-5.72%), respectively. CONCLUSIONS The discontinuation rate of tadalafil alone or in combination with ABs for LUTS with or without ED was relatively low and varied according to the study type. Patients receiving monotherapy or combination therapy were similarly likely to abandon treatment. Treatment with a fixed-dose combination was associated with better persistence than with a free-dose combination. These data may help guide clinicians in selecting drug regimens when making decisions. Factors associated with treatment withdrawal need to be determined through high-quality clinical studies to reduce the drug discontinuation rate, which will ultimately reduce healthcare costs and improve patient outcomes.
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Affiliation(s)
- Qiang Chen
- Department of Andrology & Sexual Medicine, First Affiliated Hospital of Fujian Medical University, Chazhong Road No. 20, Fuzhou 350005, Fujian, China
| | - Yinjun Mao
- Department of Pharmacy, First Affiliated Hospital of Fujian Medical University, Chazhong Road No. 20, Fuzhou 350005, Fujian, China
| | - Huiliang Zhou
- Department of Andrology & Sexual Medicine, First Affiliated Hospital of Fujian Medical University, Chazhong Road No. 20, Fuzhou 350005, Fujian, China
| | - Songxi Tang
- Department of Andrology & Sexual Medicine, First Affiliated Hospital of Fujian Medical University, Chazhong Road No. 20, Fuzhou 350005, Fujian, China
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Honda M, Kimura Y, Teraoka S, Kawamoto B, Morizane S, Hikita K, Takenaka A. Efficacy of Combination Treatment with Tadalafil and Mirabegron in Patients with Benign Prostatic Hyperplasia Who Presented with Persistent Storage Symptoms After Tadalafil Monotreatment: A Prospective, Multicenter, Open-Labeled Study. Yonago Acta Med 2022; 65:231-237. [DOI: 10.33160/yam.2022.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 07/20/2022] [Indexed: 11/05/2022]
Affiliation(s)
- Masashi Honda
- Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Yusuke Kimura
- Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Shogo Teraoka
- Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Bunya Kawamoto
- Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Shuichi Morizane
- Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Katsuya Hikita
- Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Atsushi Takenaka
- Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
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Cui J, Cao D, Bai Y, Wang J, Yin S, Wei W, Xiao Y, Wang J, Wei Q. Efficacy and Safety of 12-week Monotherapy With Once Daily 5 mg Tadalafil for Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: Evidence-based Analysis. Front Med (Lausanne) 2021; 8:744012. [PMID: 34712682 PMCID: PMC8545998 DOI: 10.3389/fmed.2021.744012] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 09/06/2021] [Indexed: 02/05/2023] Open
Abstract
Background: Tadalafil has been approved for the treatment of benign prostatic hyperplasia (BPH) for nearly 10 years. However, there are insufficient evidence-based studies of the efficacy and safety of tadalafil in treating lower urinary tract symptoms of BPH (LUTS/BPH). Objective: To evaluate the therapeutic effect and clinical safety of tadalafil monotherapy (5 mg once daily for 12 weeks) for LUTS/BPH. Methods: A total of 13 studies (15 randomized clinical trials [RCTs]) were extracted from the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science for the period up to July 2021. The quality of the included RCTs was evaluated independently by two authors, who, respectively, extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles. Conflicts were settled by a discussion with two-third of senior authors. All data analyses were conducted by the Review Manager, version 5.4. Results: Regarding efficacy, 12-week trials indicated that 5 mg once daily tadalafil showed a significantly lower and, consequently, better total International Prostate Symptom Score (IPSS) than the placebo did (mean difference [MD]: -1.97, 95% CI: -2.24 to -1.70; P < 0.00001). In addition, significant differences were found between the tadalafil regimen and the placebo in the IPSS voiding subscore (MD: -1.30, 95% CI: -1.48 to -1.11; P < 0.00001), the IPSS storage subscore (MD: -0.70, 95% CI: -0.82 to -0.58; P < 0.00001), the IPSS quality of life (MD: -0.29, 95% CI: -0.35 to -0.22; P < 0.00001), and BPH impact index (MD: -0.58, 95% CI: -0.76 to -0.40; P < 0.00001). The safety analysis did not show a significant difference in serious adverse events between the two groups (risk ratio: 1.27, 95% CI: 0.80-2.01; P = 0.31), although the adverse events occurred at a higher incidence in the tadalafil group than in the placebo. Conclusions: This study demonstrates that once daily 5 mg tadalafil is a potentially effective and safe treatment choice with excellent tolerability for patients with LUTS/BPH. Systematic Review Registration: Identifier (CRD42021228840).
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Affiliation(s)
| | | | | | | | | | | | | | - Jia Wang
- Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China
| | - Qiang Wei
- Department of Urology, Institute of Urology, West China Hospital of Sichuan University, Chengdu, China
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Narukawa T, Soh J, Kanemitsu N, Harikai S, Fujihara A, Ukimura O. Efficacy of testosterone replacement therapy plus alternate-day tadalafil for patients with late-onset hypogonadism: An open-label, randomized, crossover study. Int J Urol 2020; 28:376-381. [PMID: 33342003 DOI: 10.1111/iju.14468] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 11/19/2020] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To examine the efficacy and safety of combination treatment with testosterone replacement therapy plus alternate-day tadalafil (10 mg) in patients with late-onset hypogonadism. METHODS In this open-label, randomized, crossover study, 29 patients with late-onset hypogonadism were randomly assigned to receive testosterone replacement therapy for 12 weeks followed by combination treatment for 12 weeks (Group 1) or combination treatment for 12 weeks followed by testosterone replacement therapy (Group 2). Symptom questionnaires were administered and blood tests were performed prior to and following each treatment to assess safety and efficacy. At the end of the study, participants were asked about their treatment preferences. RESULTS An adverse effect, a rheum symptom, occurred in only one participant, and 26 participants completed the study without any toxicity. Scores on the Aging Male Symptoms scale and the modified short version of the International Index of Erectile Function, and Overactive Bladder Symptom scores were significantly improved in the combination treatment phase of Group 2, whereas no significant difference between the phases were observed in Group 1. In total, 12 out of the 14 participants in Group 1 and 11 out of the 12 participants in Group 2 preferred combination treatment, which reached statistical significance (P = 0.008 and 0.004 for Groups 1 and 2, respectively). CONCLUSIONS Testosterone replacement therapy with add-on alternate-day tadalafil is a safe and satisfactory treatment for patients with late-onset hypogonadism.
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Affiliation(s)
- Tsukasa Narukawa
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Kyoto, Japan
| | - Jintetsu Soh
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Kyoto, Japan
| | - Noriyuki Kanemitsu
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Kyoto, Japan
| | - Shunji Harikai
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Kyoto, Japan
| | - Atsuko Fujihara
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Kyoto, Japan
| | - Osamu Ukimura
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Kyoto, Japan
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Sebastianelli A, Spatafora P, Morselli S, Vignozzi L, Serni S, McVary KT, Kaplan S, Gravas S, Chapple C, Gacci M. Tadalafil Alone or in Combination with Tamsulosin for the Management for LUTS/BPH and ED. Curr Urol Rep 2020; 21:56. [PMID: 33108544 PMCID: PMC7591403 DOI: 10.1007/s11934-020-01009-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2020] [Indexed: 12/18/2022]
Abstract
Purpose of Review Aim of our systematic review is to evaluate and summarize the efficacy and safety of tadalafil alone or in combination with tamsulosin for the management of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). Recent Findings Daily tadalafil, in particular 5 mg, according to retrieved studies, appears to be both safe and effective in treating LUTS/BPH and ED, compared with placebo or tamsulosin. The combination of daily tadalafil 5 mg and tamsulosin 0.4 mg allows a better improvement of LUTS compared with both the monotherapies, even if with an increased, but acceptable and tolerated, adverse events rate. After discontinuation of tamsulosin or tadalafil in patients previously treated with their combination, the improvement of LUTS retains significance compared with baseline. Summary Tadalafil 5 mg should be considered a primary treatment option for patients with LUTS/BPH and ED. Evidence highlight an excellent tolerability, safety, and effectiveness profile, both alone or in combination with tamsulosin 0.4 mg. A better efficacy on LUTS relief has been observed for combination therapy, preserving also sexual function. The further switch to monotherapy allows to preserve LUTS relief, but tadalafil only is able to retain ED improvement. Our results support the evidence for a more and more tailored and modular LUTS treatment.
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Affiliation(s)
- A Sebastianelli
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy
- Department of Experimental and Clinical Biomedical Science, University of Florence, Florence, Italy
| | - P Spatafora
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy
- Department of Experimental and Clinical Biomedical Science, University of Florence, Florence, Italy
| | - S Morselli
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy
- Department of Experimental and Clinical Biomedical Science, University of Florence, Florence, Italy
| | - L Vignozzi
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio," Andrology, Women's Endocrinology and Gender Incongruence Unit, Careggi Hospital, University of Florence, Florence, Italy
| | - S Serni
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy
- Department of Experimental and Clinical Biomedical Science, University of Florence, Florence, Italy
| | - K T McVary
- Department of Urology, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA
| | - S Kaplan
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
| | - S Gravas
- Department of Urology, University of Thessaly, Larissa, Greece
| | - C Chapple
- Department of Urology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Mauro Gacci
- Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy.
- Department of Experimental and Clinical Biomedical Science, University of Florence, Florence, Italy.
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Singh I, Tk A, Gupta S. Efficacy and safety of tadalafil vs tamsulosin in lower urinary tract symptoms (LUTS) as a result of benign prostate hyperplasia (BPH)-open label randomised controlled study. Int J Clin Pract 2020; 74:e13530. [PMID: 32542854 DOI: 10.1111/ijcp.13530] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/05/2020] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION & AIM Several newer medications have emerged for the management of lower urinary tract symptoms secondary to benign prostate hyperplasia (BPH). The efficacy/safety of PDE-5 inhibitors (Tadalafil 5 mg) in BPH-lower urinary tract symptoms (LUTS) has been sparingly assessed in the published English literature as compared with their established role in erectile dysfunction. We aim to assess the efficacy/safety of tadalafil vs tamsulosin in symptomatic patients of BPH in a tertiary care teaching institution. METHODS After obtaining an informed written consent and institutional ethics clearance, 100 patients of BPH with an IPSS score of more than 7, without any complications of the disease were computer randomised to receive therapy with either tamsulosin 0.4 mg or tadalafil 5 mg once daily for a period of 2 months. They were evaluated for its efficacy (IPSS, Peak flow rate, IIEF-5, quality of life index [QOL] and PVR) and safety (side effect profile) with monthly visit assessments for 2 months. Data were analysed statistically using ANOVA and unpaired t-tests.The protocol was registered with the CTRI/2018/03/012825. RESULTS Patients in both groups were comparable on basis of their demographic data, renal function, PSA and baseline efficacy parameters. Significant improvements were visualised amongst/within both groups for IPSS, however the intergroup improvement was not significant (P = .096). Similar trends were seen with peak flow rate and PVR with intergroup improvement differences not being significant (P = .552 and P = .131, respectively).Improvements in QOL index were more significant in the tamsulosin group (mean difference -2.3 vs -3.06 P = .010).The adverse effects were minor and were managed symptomatically without any drug discontinuity. CONCLUSIONS In summary, therefore, we may conclude that that once daily monotherapy with tadalafil 5 mg or tamsulosin 0.4 mg was equally efficacious in the management of moderate to severely bothersome LUTS in majority of patients as a result of BPH. The role of Tadalafil monotherapy in BPH patients with predominant storage LUTS merits further evaluation with larger trials.
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Affiliation(s)
- Iqbal Singh
- Department of Surgery (Urology), University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, India
| | - Aravind Tk
- Department of Surgery (Urology), University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, India
| | - Sanjay Gupta
- Department of Surgery (Urology), University College of Medical Sciences (University of Delhi) & GTB Hospital, Delhi, India
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Takahashi R, Sumino Y, Miyazato M, Nishii H, Oshiro T, Mimata H, Saito S, Yoshida M, Eto M. Tadalafil Improves Nocturia and Nocturia-Related Quality of Life in Patients with Benign Prostatic Hyperplasia (KYU-PRO Study). Urol Int 2020; 104:587-593. [PMID: 32485724 DOI: 10.1159/000506489] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 02/04/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Tadalafil improves lower urinary tract symptoms (LUTS) including nocturia. However, the effect of tadalafil on the nocturia-related quality of life (QoL) is still unknown. OBJECTIVE The effects of tadalafil on nocturia and nocturia-related QoL were evaluated prospectively in patients with benign prostatic hyperplasia (BPH) as a multicenter study. METHODS Eligible men were ≥40 years with nocturia ≥2 and a prostate volume ≥20 mL. Patients were asked to complete a self-report questionnaire on the International Prostate Symptom Score (IPSS), the Nocturia Quality of Life questionnaire (N-QoL) and the International Index of Erectile Function 5 (IIEF5). Urinary frequency volume charts (FVCs) were also evaluated. These measures were evaluated at baseline, and after 4, 8, and 12 weeks of tadalafil administration (5 mg once daily). RESULTS Thirty-one patients with a mean age of 74 years, a mean prostate volume of 31 mL, and a mean prostate-specific antigen level of 2.8 ng/mL were included. Treatment with tadalafil significantly improved their nocturia after 4 weeks, and these improvements were maintained for the 12-week treatment period. Total N-QoL score in new patients and several N-QoL items (inadequate sleep at night and overall bother) in all patients improved significantly after tadalafil treatment. FVCs revealed a significant improvement in the number of hours of undisturbed sleep (HUS) after treatment with tadalafil. No serious adverse events were observed. CONCLUSIONS This study indicates that tadalafil 5 mg once daily improves nocturia, nocturia-related QoL, and HUS in BPH patients with nocturia. These results suggest that tadalafil can offer a clinically meaningful treatment option for BPH patients with nocturia.
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Affiliation(s)
| | - Yasuhiro Sumino
- Department of Urology, National Hospital Organization Oita Medical Center, Oita, Japan
| | - Minoru Miyazato
- Department of Systems Physiology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
| | - Hisae Nishii
- Department of Urology, National Center for Geriatrics and Gerontology, Obu, Japan
| | - Takuma Oshiro
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
| | - Hiromitsu Mimata
- Department of Urology, Oita University Faculty of Medicine, Oita, Japan
| | - Seiichi Saito
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
| | - Masaki Yoshida
- Department of Urology, National Center for Geriatrics and Gerontology, Obu, Japan
| | - Masatoshi Eto
- Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Yamazaki H, Tsujimoto N, Koyanagi M, Katoh MC, Tajima K, Komori M. Real-World Safety and Effectiveness of Tadalafil in Patients with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Japanese Post-Marketing Surveillance Study. Pragmat Obs Res 2020; 11:45-54. [PMID: 32440247 PMCID: PMC7210025 DOI: 10.2147/por.s237821] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 03/13/2020] [Indexed: 11/23/2022] Open
Abstract
Objective To evaluate the long-term safety and effectiveness of tadalafil in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia in real-world clinical practice; and to investigate the safety profile in patients aged ≥75 years. Patients and Methods This was a prospective, non-interventional, multicenter, post-marketing surveillance study in which Japanese patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia were observed for up to 18 months after initiating tadalafil treatment. The real-world safety and effectiveness outcomes were assessed at baseline and at 1, 3, 6, 12, and 18 months post-treatment or the last day of treatment. Results Most patients received tadalafil 5 mg per day throughout the observation period. Among 1393 patients analyzed for safety, the overall incidence of adverse drug reactions was 8.3%. These adverse drug reactions were generally consistent with the known safety profile of tadalafil and no new safety risks were identified in long-term use. There was no statistical difference in the frequency of adverse drug reactions between patients aged <75 and ≥75 years. The mean change in total International Prostate Symptom Score (IPSS) and IPSS-quality of life subscore was significantly improved at each timepoint. At 18 months, IPSS had improved by 5.0 points (P < 0.001) and IPSS-quality of life subscore had improved by 1.5 points (P < 0.001). The mean change in post-voiding residual urine volume from baseline was significant at each time point and was −9.8 mL at 18 months (P < 0.001); there were no significant differences from baseline in maximum urinary flow rate. Conclusion This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. In addition, safety profiles in patients aged ≥75 years were similar to patients aged <75 years.
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Affiliation(s)
- Hiroyoshi Yamazaki
- Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan
| | - Naoto Tsujimoto
- Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan
| | - Momoha Koyanagi
- Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan
| | - Megumi C Katoh
- Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan
| | - Koyuki Tajima
- Post Marketing Surveillance Clinical Research Department, Nippon Shinyaku Co., Ltd., Kyoto, Japan
| | - Mika Komori
- Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan
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Dearakhshandeh N, Mogheiseh A, Nazifi S, Ahrari Khafi MS, Abbaszadeh Hasiri M, Golchin-Rad K. Treatment of experimentally induced benign prostatic hyperplasia with Tadalafil and castration in dogs. Theriogenology 2019; 142:236-245. [PMID: 31711694 DOI: 10.1016/j.theriogenology.2019.10.040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 09/27/2019] [Accepted: 10/31/2019] [Indexed: 12/12/2022]
Abstract
New methods are being developed for the treatment of benign prostatic hyperplasia (BPH) in dogs. The aim of the present study was to evaluate the effects of Tadalafil on the treatment of experimentally induced BPH in dogs. Twenty-five adult intact male dogs were randomly divided into five groups (n = 5): normal group; dogs induced with BPH and treated with Tadalafil (5 mg/day p.o.); dogs which received Tadalafil (5 mg/day p.o.); dogs induced with BPH and treated with castration; and dogs induced with BPH. For 4 sequential weeks, the hematologic and prostate-specific factors (dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), serum prostatic acid phosphatase (PAP), and canine prostatic specific esterase (CPSE)) were measured. Significant differences were observed in the level of PSA, CPSE, and PAP concentration between the normal vs. BPH-Tadalafil, BPH-castrated, and BPH groups. Treating BPH-induced dogs with Tadalafil or castration significantly declined the serum PSA, CPSE, and PAP levels compared to those of the untreated BPH-induced group. The treatment of normal dogs with Tadalafil did not affect prostate-specific biomarkers in comparison with normal dogs. In conclusion, and according to the prostatic indices, it could be stated that Tadalafil, compared with castration, could be used for the treatment of BPH in dogs.
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Affiliation(s)
- Nooshin Dearakhshandeh
- Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Fars, Iran
| | - Asghar Mogheiseh
- Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Fars, Iran.
| | - Saeed Nazifi
- Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Fars, Iran
| | | | | | - Kamran Golchin-Rad
- Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Fars, Iran
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Negoro H, Goto T, Akamatsu S, Terada N, Kobayashi T, Matsui Y, Yamamoto T, Omura T, Yonezawa A, Matsubara K, Ogawa O. Add-on effects of tadalafil in tamsulosin-treated patients with small benign prostatic enlargement: A randomized, placebo-controlled, double-blind, crossover study. Neurourol Urodyn 2019; 39:237-242. [PMID: 31578771 DOI: 10.1002/nau.24175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 09/15/2019] [Indexed: 01/05/2023]
Abstract
AIM To assess the add-on effects of tadalafil in patients with a relatively small benign prostatic enlargement (BPE) treated with tamsulosin. METHODS From September 2014 to July 2018, we prospectively studied patients (aged 50 years or more) attending our hospital who had received tamsulosin for small BPE (20-40 mL) for 4 weeks at least and still had residual lower urinary tract symptoms (LUTS) with total International Prostate Symptom Scores (IPSS) of at least 8 and IPSS-quality of life scores at least 3. We randomized eligible patients into two groups: one of which received tadalafil 5 mg once daily for 6 weeks, followed by placebo for 6 weeks, and the other of which received placebo followed by tadalafil in the same manner. The patients were reviewed at our outpatient clinic after 2, 6, 8, and 12 weeks. RESULTS There were 13 patients in the tadalafil-placebo and 13 in the placebo-tadalafil group. Their median ages (range) were 70 (65-85) and 73 (50-80) years, prostatic volumes (median) 30.0 (22.0-39.7) and 32.0 (20.1-39.5) mL, and total IPSS (median) 17 (10-27) and 16 (10-24), respectively. The primary endpoints, namely mean changes of total IPSS from baseline, were 1.85 on placebo and -3.42 on tadalafil; this difference is statistically significant (difference: -1.57; 95% confidence interval: -3.00, -0.69; P = .032). We encountered no adverse effects. CONCLUSIONS Add-on of tadalafil for symptomatic patients with small BPE treated with tamsulosin appears to be effective and safe.
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Affiliation(s)
- Hiromitsu Negoro
- Department of Urology, Kyoto University Hospital, Kyoto, Japan.,Department of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Takayuki Goto
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
| | | | - Naoki Terada
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
| | | | | | - Takashi Yamamoto
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan
| | - Tomohiro Omura
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan
| | - Atsushi Yonezawa
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan
| | - Kazuo Matsubara
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan
| | - Osamu Ogawa
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
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Yang DY, Jeong HC, Ko K, Lee SH, Lee SK, Shin TY, Cho JS, Lee WK. Effect of tadalafil 5 mg on post-micturition dribble in men with lower urinary tract symptoms: a multicentre, double-blind, randomized, placebo-controlled trial. BJU Int 2019; 124:862-869. [PMID: 31207030 DOI: 10.1111/bju.14849] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To compare the effects of taking tadalafil 5 mg and placebo once daily on post-micturition dribble (PMD) in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS Our prospective, randomized, double-blind, placebo-controlled, multicentre trial enrolled 102 men with PMD and other LUTS. PMD was assessed using the Hallym Post-Micturition Dribble Questionnaire (HPMDQ) and according to PMD volume. Over a 12-week period, patients took either tadalafil 5 mg (n = 51) or placebo (n = 51) once daily and their HPMDQ and PMD volume results were evaluated. Adverse events (AEs) were also reported. RESULTS Over the course of 12 weeks, total HPMDQscores and PMD volumes improved significantly more in the tadalafil group than in the placebo group (reduction of total HPMDQ score of ≥2 points in the tadalafil and placebo group in 68.8% and 31.9% of patients (P < 0.001) and decreased mean PMD volume in the tadalafil and placebo group at 0.48 mL and 0.22 mL, respectively (P = 0.046). Specifically, PMD frequency decreased and quality of life increased significantly more in the tadalafil group than in the placebo group (P = 0.029 and P < 0.001, respectively). Furthermore, 66.7% of the tadalafil group reported moderate and significant PMD improvement, whereas only 4.2% reported that tadalafil was ineffective. Treatment-emergent AEs did not significantly differ between the groups (all P > 0.05), and no serious AEs were observed. CONCLUSION Taking tadalafil 5 mg once daily reduced PMD symptom severity and PMD volume in men with PMD, without inducing serious AEs, more effectively than placebo, suggesting that taking tadalafil 5 mg once daily may be an effective and well-tolerated PMD treatment.
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Affiliation(s)
- Dae Yul Yang
- Department of Urology, College of Medicine, Kangdong Sacred Heart Hospital, Hallym Unversity, Seoul, Korea
| | - Hyun Cheol Jeong
- Department of Urology, College of Medicine, Kangdong Sacred Heart Hospital, Hallym Unversity, Seoul, Korea
| | - Kyungtae Ko
- Department of Urology, College of Medicine, Kangdong Sacred Heart Hospital, Hallym Unversity, Seoul, Korea
| | - Seong Ho Lee
- Department of Urology, College of Medicine, Dongtan Sacred Heart Hospital, Hallym Unversity, Hwaseong, Korea
| | - Sang Kon Lee
- Department of Urology, College of Medicine, Chuncheon Sacred Heart Hospital, Hallym Unversity, Chuncheon, Korea
| | - Tae Young Shin
- Department of Urology, College of Medicine, Chuncheon Sacred Heart Hospital, Hallym Unversity, Chuncheon, Korea
| | - Jin Seon Cho
- Department of Urology, College of Medicine, Hallym University Sacred Heart Hospital, Hallym Unversity, Anyang, Korea
| | - Won Ki Lee
- Department of Urology, College of Medicine, Chuncheon Sacred Heart Hospital, Hallym Unversity, Chuncheon, Korea
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Gotoh D, Torimoto K, Iwasaki H, Iwamoto T, Morizawa Y, Hori S, Miyake M, Tanaka N, Hirayama A, Nishi E, Fujimoto K. Tadalafil, a phosphodiesterase type 5 inhibitor, restores urethra and detrusor function in the initial phase of diabetes in rats. Low Urin Tract Symptoms 2019; 11:241-247. [PMID: 31207119 DOI: 10.1111/luts.12272] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 05/02/2019] [Accepted: 05/11/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE This study investigated the effects of tadalafil on the urethra and detrusor in the initial phase of diabetes in rats. METHODS Thirty-six female Sprague-Dawley rats were assigned to a non-diabetes (ND), diabetes (D), or tadalafil-treated diabetes (DT) group (n = 12 per group), with the DT group receiving oral tadalafil (2 mg/kg/d) for 7 days before the experiments. Seven weeks after diabetes induction (by a single intraperitoneal injection of streptozotocin), urethral and intravesical pressure were simultaneously recorded in vivo, whereas responses of detrusor strips to potassium chloride (30 mM), electrical field stimulation (EFS) and carbachol were measured in vitro. RESULTS The intravesical pressure at which the urethra started to relax was significantly lower in the DT than D group (mean [± s.d.] 18.9 ± 2.9 vs 29.1 ± 6.6 cm H2 O; P < .05). In addition, the reduction in urethral pressure was significantly larger in the DT than D group (-10.9 ± 4.0 vs -4.0 ± 2.9 cm H2 O; P < .05). Detrusor stimulation revealed that the mean contractile responses to EFS and carbachol were significantly lower in the ND and DT groups than in the D group (120.7 ± 26.5% and 130.8 ± 15.8% vs 200.1 ± 47.9% of the 30 mM KCl-induced contraction, respectively, in response to 50 Hz EFS [P < .05]; 211.1 ± 35.4% and 208.4 ± 25.3% vs 425.7 ± 125.0% of the 30 mM KCl-induced contraction, respectively, in response to 10-3 M carbachol [P < .05]). CONCLUSIONS Tadalafil restored urethral relaxation function and detrusor responses to EFS and carbachol during the initial phase of diabetes.
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Affiliation(s)
- Daisuke Gotoh
- Department of Urology, Nara Medical University, Kashihara, Japan
| | | | - Hirotaka Iwasaki
- Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan
| | - Takashi Iwamoto
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Yosuke Morizawa
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Shunta Hori
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Makito Miyake
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Nobumichi Tanaka
- Department of Urology, Nara Medical University, Kashihara, Japan
| | | | - Eiichiro Nishi
- Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan
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MacDonald R, Brasure M, Dahm P, Olson CM, Nelson VA, Fink HA, Risk MC, Rwabasonga B, Wilt TJ. Efficacy of newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a systematic review. Aging Male 2019; 22:1-11. [PMID: 29394114 DOI: 10.1080/13685538.2018.1434503] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
We conducted a systematic review to evaluate the efficacy and adverse effects of newer drugs used to treat lower urinary tract symptoms (LUTS). The drugs were either Food and Drug Administration (FDA) approved for benign prostatic hyperplasia (BPH) or not FDA approved for BPH but have been evaluated for treatment of BPH since 2008. We searched bibliographic databases through September 2017. We included randomized controlled trials (RCTs) lasting one month or longer published in English. Outcomes of interest were LUTS assessed by validated measures. Efficacy was interpreted using established thresholds indicating clinical significance that identified the minimal detectable difference. Twenty-three unique, generally short-term, RCTs evaluating over 9000 participants were identified. Alpha-blocker silodosin and phosphodiesterase type 5 inhibitor tadalafil were more effective than placebo in improving LUTS (moderate strength evidence) but these drugs had more adverse effects, including abnormal ejaculation (silodosin). Anticholinergics were only effective versus placebo when combined with an alpha-blocker. Evidence was generally low strength or insufficient for other drugs. Evidence was insufficient to assess long-term efficacy, prevention of symptom progression, need for surgical intervention, or long-term adverse effects. Longer trials are needed to assess the effect of these therapies on response rates using established minimal detectable difference thresholds, disease progression, and harms.
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Affiliation(s)
- Roderick MacDonald
- a Center for Chronic Disease Outcomes Research , Minneapolis Veterans Affairs Healthcare System , Minneapolis , MN , USA
| | - Michelle Brasure
- b Division of Health Policy and Management , University of Minnesota, School of Public Health , Minneapolis , MN , USA
| | - Philipp Dahm
- a Center for Chronic Disease Outcomes Research , Minneapolis Veterans Affairs Healthcare System , Minneapolis , MN , USA
- c Department of Urology , University of Minnesota , Minneapolis , MN , USA
| | - Carin M Olson
- b Division of Health Policy and Management , University of Minnesota, School of Public Health , Minneapolis , MN , USA
| | - Victoria A Nelson
- b Division of Health Policy and Management , University of Minnesota, School of Public Health , Minneapolis , MN , USA
| | - Howard A Fink
- d Geriatric Research Education and Clinical Center , Minneapolis Veterans Affairs Healthcare System , Minneapolis , MN , USA
| | - Michael C Risk
- c Department of Urology , University of Minnesota , Minneapolis , MN , USA
| | - Bruce Rwabasonga
- b Division of Health Policy and Management , University of Minnesota, School of Public Health , Minneapolis , MN , USA
| | - Timothy J Wilt
- a Center for Chronic Disease Outcomes Research , Minneapolis Veterans Affairs Healthcare System , Minneapolis , MN , USA
- e Department of Medicine , University of Minnesota , Minneapolis , MN , USA
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16
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[EFFECTIVENESS AND SAFETY OF TADALAFIL IN VERY ELDERLY PATIENTS WITH LOWER URINARY TRACT SYMPTOMS]. Nihon Hinyokika Gakkai Zasshi 2019; 110:106-111. [PMID: 32307377 DOI: 10.5980/jpnjurol.110.106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
(Aim) The α-1 blockers have been used as first-line therapy for benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). A new phosphodiesterase type 5 inhibitor, tadalafil, was approved in 2014 and received a Grade A recommendation in the 2017 clinical practice guidelines for LUTS. In this study, we examined the effectiveness and safety of tadalafil in very elderly patients with LUTS. (Subjects and methods) The subjects were 84 very elderly patients, at least 75 years of age, with BPH/LUTS for which they had been administered tadalafil.Data of the 71 patients were retrospectively reviewed in terms of the International Prostate Symptom Score (IPSS), quality of life (QOL) index, overactive bladder symptom score (OABSS), maximum flow rate and postvoid residual urine volume at baseline and at weeks 4, 8, 12, and 24. We also examined the safety of tadalafil therapy. (Results) Patient characteristics were: median age 80.1±4.38 years, prostate volume 41.2±24.3 cc and IPSS 15.7±5.68. Patients who had undergone treatment for BPH/LUTS prior to tadalafil therapy accounted for 67.9% of the study population.Significant improvements occurred in IPSS, QOL and OABSS at week 4, and the improvements were maintained until week 24. As for postvoid residual urine test results, a significant improvement was seen at week 8 only.Adverse events were noted in 9 patients (10.7%), but only 5 (6.0%) needed to discontinue tadalafil therapy. (Conclusion) Tadalafil is considered to be a highly effective and safe drug in very elderly patients with LUTS.
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17
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Zhang Z, Li H, Zhang X, Dai Y, Park HJ, Jiann BP, Li P, Lou Y, Ye Z, Viktrup L. Efficacy and safety of tadalafil 5 mg once-daily in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction: A phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study. Int J Urol 2018; 26:192-200. [PMID: 30362173 DOI: 10.1111/iju.13828] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 09/19/2018] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of tadalafil in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction. METHODS The present phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study was carried out at 40 study centers in the Asia-Pacific region (mainland China, Taiwan and Korea; NCT01937871). Participants were randomized to receive a placebo (n = 361), tadalafil 5 mg (n = 362) or tamsulosin 0.2 mg (n = 185) in a 2:2:1 ratio for 12 weeks. RESULTS A total of 909 Asian men were randomized into three groups. After 12 weeks of treatment, a statistically significant improvement in least squares mean change from baseline in total International Prostate Symptom Score was observed in the tadalafil versus the placebo group (-5.49 vs -4.08, respectively; P < 0.001). A statistically significant improvement in the change from baseline for the International Index of Erectile Function-Erectile Function domain score, was observed in tadalafil compared with the placebo at 12 weeks (5.24 vs 1.88, respectively; P < 0.001). A significant improvement was observed in the change from baseline in the percentage of "Yes" responses to Sexual Encounter Profile questions 2 and 3 in the tadalafil versus placebo group at 12 weeks (23.87% vs 10.90%; P < 0.001 and 36.62% vs 15.96%; P < 0.001, respectively). Safety results were consistent with the known tadalafil safety profile. CONCLUSIONS Tadalafil is efficacious and well tolerated in the treatment of Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction.
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Affiliation(s)
- Zhichao Zhang
- Andrology Center, Peking University First Hospital, Peking University, Beijing, China
| | - Hanzhong Li
- Peking Union Medical College Hospital, Beijing, China
| | - Xiaodong Zhang
- Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yutian Dai
- Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China
| | - Hyun Jun Park
- Department of Urology, Pusan National University Hospital, Busan, Korea
| | | | - Peng Li
- Eli Lilly Suzhou Pharmaceutical, Shanghai, China
| | - Ying Lou
- Eli Lilly Suzhou Pharmaceutical, Shanghai, China
| | - Zhangqun Ye
- Department of Urology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lars Viktrup
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
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18
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Takahashi R, Miyazato M, Nishii H, Sumino Y, Takayama K, Onzuka M, Oshiro T, Saito S, Fujimoto N, Mimata H, Eto M. Tadalafil Improves Symptoms, Erectile Function and Quality of Life in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (KYU-PRO Study). Low Urin Tract Symptoms 2018; 10:76-83. [PMID: 29341501 DOI: 10.1111/luts.12143] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 04/28/2016] [Accepted: 05/09/2016] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Effect of tadalafil on lower urinary tract symptoms (LUTS), erectile function and quality of life (QoL) were prospectively evaluated in patients with benign prostatic hyperplasia (BPH) at multicenter. METHODS Eligible men were ≥40 years who had no treatment with alpha-blocker for BPH, with total International Prostate Symptom Score (IPSS) ≥8, IPSS-QOL ≥2 and prostate volume ≥20 mL. Data were collected on age, body mass index (BMI), and prostate specific antigen (PSA). Patients were asked to complete a self-reported questionnaire regarding the IPSS, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), and Medical Outcome Study 8-Item Short-Form Health Survey (SF-8). These measures were assessed at baseline, 4-, 8-, 12-week of tadalafil treatment. In addition, uroflowmetry was also performed at baseline, and 12-week end point visit. RESULTS Thirty five patients with mean age 67.3 years, mean BMI 23.6 kg/m2 , mean prostate volume 36 mL, and mean PSA 3.4 ng/mL were enrolled. Treatment with tadalafil significantly improved IPSS total score, IPSS voiding subscore, IPSS storage subscore, OABSS and IPSS-QoL score after 4 weeks and these improvements were maintained for 12-week treatment period. IIEF5 score and general health in SF-8 are significantly improved with the treatment of tadalafil. However, maximum flow rate and postvoiding residual volume were not significantly changed. There were not any serious adverse events. CONCLUSIONS These results indicate that tadalafil 5 mg once daily would be effective and well tolerated treatment in Japanese men with BPH-LUTS.
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Affiliation(s)
- Ryosuke Takahashi
- Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Minoru Miyazato
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Hisae Nishii
- Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yasuhiro Sumino
- Department of Urology, Oita University Faculty of Medicine, Oita, Japan
| | - Kazuo Takayama
- Department of Urology, Takayama Hospital, Fukuoka, Japan
| | - Masako Onzuka
- Department of Urology, Kano Hospital, Fukuoka, Japan
| | - Takuma Oshiro
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Seiichi Saito
- Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Naohiro Fujimoto
- Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Hiromitsu Mimata
- Department of Urology, Oita University Faculty of Medicine, Oita, Japan
| | - Masatoshi Eto
- Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Yokoyama O, Ozeki A, Suzuki N, Murakami M. Early improvement of storage or voiding symptoms by tadalafil predicts treatment outcomes in patients with lower urinary tract symptoms from benign prostatic hyperplasia. Int J Urol 2017; 25:240-245. [DOI: 10.1111/iju.13487] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 10/01/2017] [Indexed: 11/26/2022]
Affiliation(s)
- Osamu Yokoyama
- Department of Urology; Faculty of Medical Science; University of Fukui; Fukui Japan
| | - Akichika Ozeki
- Medicines Development Unit Japan; Biometics; Asia Pacific Statistical Science-Japan; Eli Lilly Japan K.K.; Kobe Japan
| | - Nahoko Suzuki
- Medicines Development Unit Japan; Biometics; Japan Scientific Communications Biomedicines; Eli Lilly Japan K.K.; Tokyo Japan
| | - Masahiro Murakami
- Medicines Development Unit; Eli Lilly and Company; Indianapolis Indiana USA
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Won JE, Chu JY, Choi HC, Chen Y, Park HJ, Dueñas HJ. Safety and Effectiveness of Once-Daily Tadalafil (5 mg) Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post-Marketing Surveillance Study. World J Mens Health 2017; 36:161-170. [PMID: 28879692 PMCID: PMC5924958 DOI: 10.5534/wjmh.17017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 07/13/2017] [Accepted: 07/25/2017] [Indexed: 12/17/2022] Open
Abstract
Purpose The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. Materials and Methods This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. Results All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, the mean IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (p<0.0001), with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Conclusions Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.
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Affiliation(s)
| | | | | | - Yun Chen
- Lilly Suzhou Pharmaceutical Company, Shanghai, China
| | - Hyun Jun Park
- Department of Urology, Pusan National University School of Medicine, Busan, Korea.
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Homma Y, Gotoh M, Kawauchi A, Kojima Y, Masumori N, Nagai A, Saitoh T, Sakai H, Takahashi S, Ukimura O, Yamanishi T, Yokoyama O, Yoshida M, Maeda K. Clinical guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia. Int J Urol 2017; 24:716-729. [DOI: 10.1111/iju.13401] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 05/23/2017] [Indexed: 12/29/2022]
Affiliation(s)
- Yukio Homma
- Department of Urology; Graduate School of Medicine; The University of Tokyo; Tokyo Japan
| | - Momokazu Gotoh
- Department of Urology; Nagoya University Graduate School of Medicine; Nagoya Japan
| | | | - Yoshiyuki Kojima
- Department of Urology; Fukushima Prefectural University of Medicine; Fukushima Japan
| | - Naoya Masumori
- Department of Urology; Sapporo Medical University School of Medicine; Sapporo Japan
| | - Atsushi Nagai
- Department of Urology; Kawasaki Medical School; Kurashiki Japan
| | | | - Hideki Sakai
- Department of Urology; Nagasaki University; Nagasaki Japan
| | | | - Osamu Ukimura
- Department of Urology; Kyoto Prefectural University of Medicine; Kyoto Japan
| | | | | | - Masaki Yoshida
- Department of Urology; National Center of Geriatrics and Gerontology; Obu Japan
| | - Kenji Maeda
- Department of Urology; Maeda Clinic of Internal Medicine; Ageo Japan
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22
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Takeda M, Yokoyama O, Yoshida M, Nishizawa O, Hirata K, Nakaoka R, Takita Y, Murakami M. Safety and efficacy of the combination of once-daily tadalafil and alpha-1 blocker in Japanese men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A randomized, placebo-controlled, cross-over study. Int J Urol 2017; 24:539-547. [DOI: 10.1111/iju.13357] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 03/21/2017] [Indexed: 11/27/2022]
Affiliation(s)
- Masayuki Takeda
- Department of Urology; Division of Clinical Research; Graduate Faculty of Interdisciplinary Research; University of Yamanashi; Yamanashi Japan
| | - Osamu Yokoyama
- Department of Urology; Faculty of Medical Science; University of Fukui; Fukui Japan
| | - Masaki Yoshida
- Department of Urology; National Center for Geriatrics and Gerontology; Obu Japan
| | - Osamu Nishizawa
- Department of Urology; North Alps Medical Center Azumi Hospital; Kitaazumigun Ikedamachi Japan
| | - Kinya Hirata
- Clinical Development Department Tokyo; Nippon Shinyaku; Tokyo Japan
| | - Ryuhei Nakaoka
- Biostatistics and Data Management Department; Nippon Shinyaku; Kyoto Japan
| | - Yasushi Takita
- Asia-Pacific Statistical Science, Medicines Development Unit-Japan; Eli Lilly Japan; Kobe Japan
| | - Masahiro Murakami
- Medicines Development Unit; Eli Lilly and Company; Indianapolis Indiana USA
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YOSHIDA M, ORIGASA H, SEKI N. Comparison of Silodosin versus Tadalafil in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia. Low Urin Tract Symptoms 2017; 9:176-186. [DOI: 10.1111/luts.12177] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 02/09/2017] [Accepted: 03/01/2017] [Indexed: 11/27/2022]
Affiliation(s)
- Masaki YOSHIDA
- Department of Urology; National Center for Geriatrics and Gerontology; Obu-City Japan
| | - Hideki ORIGASA
- Department of Biostatistics and Clinical Epidemiology; The University of Toyama Graduate School of Medicine and Pharmaceutical Sciences; Toyama Japan
| | - Narihito SEKI
- Department of Urology; Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers; Fukuoka Japan
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Yoshida T, Kinoshita H, Shimada S, Taguchi M, Matsuda T. Comparison of Silodosin Monotherapy vs Silodosin With Tadalafil Add-on Therapy in Patients With Benign Prostatic Hyperplasia. Urology 2017; 106:153-159. [PMID: 28431996 DOI: 10.1016/j.urology.2017.04.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 04/05/2017] [Accepted: 04/08/2017] [Indexed: 01/31/2023]
Abstract
OBJECTIVE To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil for patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) treated with the α1-adrenoceptor blocker silodosin. MATERIALS AND METHODS We analyzed 103 patients with LUTS/BPH with an International Prostate Symptom Score (IPSS) of >8 after ≥4 weeks of silodosin treatment from April 2016 through December 2016 at Kori Hospital. The patients subsequently received silodosin 4.0 mg twice daily (monotherapy group) or silodosin 4.0 mg twice daily plus tadalafil 5.0 mg once daily (add-on therapy group) for 8 weeks. We assessed adverse events and evaluated the mean change from baseline to 8 weeks in the IPSS, Overactive Bladder Symptom Score (OABSS), maximum urine flow rate (Qmax), and post-void residual urine volume. RESULTS Of 103 patients, 101 (98.1%) could continue medical treatment. The IPSS, OABSS, and Qmax showed significantly greater improvement in the add-on therapy than in the monotherapy group (-3.92 vs -1.24, -1.18 vs 0.10, and 1.09 vs -1.04, respectively; all P <.05). Although 4 patients experienced adverse events (add-on therapy: n = 3, 5.7%; monotherapy: n = 1, 2.0%), no significant differences were observed (P = .62). Among patients with overactive bladder (n = 55), the IPSS storage symptom subscore, IPSS urgency subscore, and OABSS urgency subscore showed significantly greater improvement in the add-on therapy than in the monotherapy group (-2.23 vs 0.17, -0.88 vs 0.28, and -1.5 vs -0.48, respectively; all P <.05). CONCLUSION Add-on therapy with tadalafil may be effective for patients with LUTS/BPH resistant to silodosin monotherapy.
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Affiliation(s)
- Takashi Yoshida
- Department of Urology and Andrology, Kori Hospital, Kansai Medical University, Osaka, Japan
| | - Hidefumi Kinoshita
- Department of Urology and Andrology, Kansai Medical University Hospital, Osaka, Japan
| | - Seiji Shimada
- Department of Urology and Andrology, Kori Hospital, Kansai Medical University, Osaka, Japan
| | - Makoto Taguchi
- Department of Urology and Andrology, Kori Hospital, Kansai Medical University, Osaka, Japan
| | - Tadashi Matsuda
- Department of Urology and Andrology, Kansai Medical University Hospital, Osaka, Japan.
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EFFECT OF TADALAFIL THAT WAS ADDITIONALLY ADMINISTERED TO PATIENTS RECEIVING AN ALPHA1-BLOCKER IN JAPANESE MEN WITH LOWER URINARY TRACT SYMPTOMS SUGGESTIVE OF BENIGN PROSTATIC HYPERPLASIA. Nihon Hinyokika Gakkai Zasshi 2017; 107:28-33. [PMID: 28132988 DOI: 10.5980/jpnjurol.107.28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
(Objectives) Alpha1-blockers have been widely used for the treatment of lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). As improvement of symptoms occur relatively early after the administration of alpha-1 blockers, the blockers are considered to be extremely beneficial. However, some patients respond poorly to the blockers, providing additional treatment is difficult. Here we examined the efficacy of tadalafil that was additionally administered to patients receiving an oral alpha-1 blocker. (Subjects and methods) The subjects were patients who had been diagnosed with BPH/LUTS, had received an oral alpha1-blocker for at least 1 month, and had responded poorly to the alpha-1 blocker treatment (International Prostate Symptom Score IPSS ≥8 and/or QOL index ≥3). Tadalafil 5 mg was administered on consecutive days to patients orally receiving an alpha-1 blocker. The following were measured before and at 4 and 8 weeks after the administration of tadalafil to evaluate the add-on effect of Tadalafil: IPSS, QOL index, Overactive Bladder Symptom Score (OABSS), maximal urinary flow rate, residual urine volume, and International Index of Erectile Function-5 (IIEF-5). (Results) We studied 41 patients until 8 weeks after the drug administration. Tadalafil produced significant improvement in IPSS, QOL index, OABSS, and IIEF-5 at 4 weeks after the administration, as compared with before administration (P < 0.05). The improvement was even more significant at 8 weeks. However, the maximal urinary flow rate or residual urine volume did not differ significantly at any time point. (Conclusions) The results of this study revealed that additional administration of tadalafil improves not only urinary conditions but also sexual function in patients with BPH/LUTS.
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Oelke M, Wagg A, Takita Y, Büttner H, Viktrup L. Efficacy and safety of tadalafil 5 mg once daily in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in men aged ≥75 years: integrated analyses of pooled data from multinational, randomized, placebo-controlled cli. BJU Int 2017; 119:793-803. [DOI: 10.1111/bju.13744] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Matthias Oelke
- Department of Urology; Hannover Medical School; Hannover Germany
| | - Adrian Wagg
- Geriatric Medicine; University of Alberta; Edmonton AB Canada
| | - Yasushi Takita
- Medicines Development Unit Japan; Eli Lilly Japan; Kobe Hyogo Japan
| | - Hartwig Büttner
- Eli Lilly Biomedicines BU - Men's Health Therapeutic Area Europe; c/o Lilly Deutschland, GmbH; Bad Homburg Germany
| | - Lars Viktrup
- Lilly Research Laboratories; Eli Lilly and Company; Indianapolis IN USA
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Wang Y, Bao Y, Liu J, Duan L, Cui Y. Tadalafil 5 mg Once Daily Improves Lower Urinary Tract Symptoms and Erectile Dysfunction: A Systematic Review and Meta-analysis. Low Urin Tract Symptoms 2016; 10:84-92. [PMID: 29341503 DOI: 10.1111/luts.12144] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 04/10/2016] [Accepted: 05/09/2016] [Indexed: 12/22/2022]
Abstract
OBJECTIVES We carried out a systematic review and meta-analysis to assess tadalafil 5 mg once-daily for the treatment of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). METHODS A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of tadalafil 5 mg once-daily for the treatment of LUTS and ED. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. RESULTS Thirteen publications involving a total of 3973 patients were used in the analysis, including 13 RCTs that compared tadalafil 5 mg once-daily with placebo. We found that tadalafil 5 mg once-daily was effective in improving LUTS suggestive of BPH and treating ED over 12 weeks in our meta-analysis. Total International Prostate Symptom Score (IPSS) (SMD = - 2.02, 95% CI = - 2.52 to -1.53, P < 0.00001); Benign Prostatic Hyperplasia Impact Index (BPH-II) (SMD = -0.58, 95% CI = -0.84 to -0.33, P < 0.00001); International Index of Erectile Function-erectile function (IIEF) domain (standardized mean difference [SMD] = 5.18, 95% confidence interval [CI] = 4.13-6.23, P < 0.00001) indicated that tadalafil 5 mg once-daily was more effective than the placebo. Safety assessments included discontinuations due to adverse event (odds ratio (OR) = 1.79, 95% CI = 1.12-2.85, P = 0.01) indicated that tadalafil 5 mg once-daily was well tolerated. CONCLUSIONS This meta-analysis indicates that tadalafil 5 mg once-daily to be an effective treatment for LUTS and ED with a low occurrence of side effects.
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Affiliation(s)
- Yilin Wang
- Biochip Laboratory, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, China
| | - Yiping Bao
- Department of Urology, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, China
| | - Jie Liu
- Biochip Laboratory, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, China
| | - Lijun Duan
- Biochip Laboratory, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, China
| | - Yuanshan Cui
- Department of Urology, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, China
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Yokoyama O, Igawa Y, Takeda M, Yamaguchi T, Murakami M, Viktrup L. Tadalafil for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a review of clinical data in Asian men and an update on the mechanism of action. Ther Adv Urol 2015; 7:249-64. [PMID: 26425140 DOI: 10.1177/1756287215589238] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, is approved worldwide for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS). The purpose of this narrative review is to summarize the clinical data on tadalafil 5 mg once-daily, primarily focusing on Asian men with BPH-LUTS, and to update the current understanding of the mechanism of action underlying PDE5 inhibition. Findings from studies have demonstrated that PDE5 is highly expressed in the lower urinary tract and supporting vasculature, and that PDE5 inhibition potentially decreases smooth muscle cell proliferation in the prostate, relaxes smooth muscle in the prostate, bladder neck and supporting vasculature, increases blood perfusion to the lower urinary tract, and modulates bladder afferent nerve activity. A total of 11 larger, 12-week, double-blind, randomized, placebo-controlled studies of tadalafil, including four Asian studies, have been conducted globally, enrolling >3000 men with BPH-LUTS. In addition, two long-term (42- and 52-week) studies enrolled 394 Japanese and 428 North American men, respectively, with BPH-LUTS. Overall, tadalafil 5 mg once-daily resulted in significant improvements in the change from baseline to endpoint in total International Prostate Symptom Scores (IPSS), IPSS storage and voiding subscores, and IPSS quality of life index compared with placebo. Tadalafil was well tolerated and had a favorable safety profile. These findings support tadalafil 5 mg once-daily for treating men, including Asian men, with BPH-LUTS.
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Affiliation(s)
- Osamu Yokoyama
- Department of Urology, Faculty of Medical Science, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan
| | - Yasuhiko Igawa
- Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Masayuki Takeda
- Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
| | | | - Masahiro Murakami
- Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Hyogo, Japan
| | - Lars Viktrup
- Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana, USA
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Masumori N. Editorial Comment from Dr Masumori to Treatment satisfaction and clinically meaningful symptom improvement in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: Secondary results from a 6-month, rand. Int J Urol 2015; 22:589. [DOI: 10.1111/iju.12765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 02/15/2015] [Indexed: 11/27/2022]
Affiliation(s)
- Naoya Masumori
- Department of Urology; Sapporo Medical University; Sapporo Japan
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30
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Roehrborn CG, Casabé A, Glina S, Sorsaburu S, Henneges C, Viktrup L. Treatment satisfaction and clinically meaningful symptom improvement in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia: Secondary results from a 6-month, randomized, double-blind study comparing finasteride plus tadalafil with finasteride plus placebo. Int J Urol 2015; 22:582-7. [PMID: 25827166 DOI: 10.1111/iju.12741] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 01/13/2015] [Accepted: 01/21/2015] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To report the secondary analyses of treatment satisfaction and clinically meaningful improvements in a randomized study comparing coadministration of tadalafil 5 mg with finasteride 5 mg versus finasteride alone in men with prostatic enlargement secondary to benign prostatic hyperplasia. METHODS An international, randomized, double-blind, parallel study was carried out in men aged ≥45 years who were 5-alpha reductase inhibitor naïve, and had an International Prostate Symptom Score ≥13 and prostate volume ≥30 mL; 350 men received placebo/finasteride and 345 received tadalafil/finasteride over 26 weeks. Treatment satisfaction was assessed per protocol using the Treatment Satisfaction Scale-Benign Prostatic Hyperplasia. Responder cut-offs, analyzed post-hoc were total International Prostate Symptom Score improvement ≥3 points or ≥25% from randomization. RESULTS Baseline patient characteristics were generally comparable between responders and non-responders. The proportion of patients with an International Prostate Symptom Score improvement ≥3 points with tadalafil/finasteride and placebo/finasteride, respectively, at week 4 was 57.0% and 47.9% (OR 1.45, 95% confidence interval 1.07-1.97), at week 12 was 68.8% and 60.7% (OR 1.48, 95% confidence interval 1.07-2.05) and at week 26 was 71.4% and 70.2% (OR 1.14, 95% confidence interval 0.81-1.61); for IPSS change ≥25%, the corresponding proportions were 44.8% and 32.9% (OR 1.66, 95% confidence interval 1.21-2.28), 55.5% and 51.9% (OR 1.18, 95% confidence interval 0.87-1.62), and 62.0% and 58.3% (OR 1.23, 95% confidence interval 0.89-1.70). Treatment satisfaction at week 26 was significantly greater with tadalafil/finasteride versus placebo/finasteride for total treatment satisfaction scale score (P=0.031) and satisfaction with efficacy subscore (P = 0.025); scores were not significantly different between treatments for satisfaction with dosing or side-effects (both P ≥ 0.371). CONCLUSIONS Tadalafil/finasteride results in significantly more patients achieving early clinical meaningful improvements in symptoms, and in greater treatment satisfaction versus placebo/finasteride.
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Affiliation(s)
| | - Adolfo Casabé
- Instituto Médico Especializado, Buenos Aires, Argentina
| | - Sidney Glina
- Instituto H. Ellis and Department of Urology, Ipiranga Hospital, Sao Paolo, Brazil
| | - Sebastian Sorsaburu
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
| | - Carsten Henneges
- Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany
| | - Lars Viktrup
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
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AIZAWA N, ITO H, SUGIYAMA R, FUJIMURA T, FUKUHARA H, KUME H, HOMMA Y, IGAWA Y. Effects of Sildenafil, a Phosphodiesterase Type 5 Inhibitor, on the Primary Single Afferent Activity of the Rat Bladder. Low Urin Tract Symptoms 2015; 9:57-61. [DOI: 10.1111/luts.12095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 01/13/2015] [Accepted: 01/20/2015] [Indexed: 12/21/2022]
Affiliation(s)
- Naoki AIZAWA
- Department of Continence Medicine; The University of Tokyo Graduate School of Medicine; Tokyo Japan
| | - Hiroki ITO
- Department of Continence Medicine; The University of Tokyo Graduate School of Medicine; Tokyo Japan
| | - Rino SUGIYAMA
- Department of Continence Medicine; The University of Tokyo Graduate School of Medicine; Tokyo Japan
| | - Tetsuya FUJIMURA
- Department of Urology; The University of Tokyo Graduate School of Medicine; Tokyo Japan
| | - Hiroshi FUKUHARA
- Department of Urology; The University of Tokyo Graduate School of Medicine; Tokyo Japan
| | - Haruki KUME
- Department of Urology; The University of Tokyo Graduate School of Medicine; Tokyo Japan
| | - Yukio HOMMA
- Department of Urology; The University of Tokyo Graduate School of Medicine; Tokyo Japan
| | - Yasuhiko IGAWA
- Department of Continence Medicine; The University of Tokyo Graduate School of Medicine; Tokyo Japan
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Nishizawa O, Yoshida M, Takeda M, Yokoyama O, Morisaki Y, Murakami M, Viktrup L. Tadalafil 5 mg once daily for the treatment of Asian men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: Analyses of data pooled from three randomized, double-blind, placebo-controlled studies. Int J Urol 2015; 22:378-84. [DOI: 10.1111/iju.12699] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 11/07/2014] [Accepted: 11/26/2014] [Indexed: 01/03/2023]
Affiliation(s)
- Osamu Nishizawa
- Department of Urology, Azumi General Hospital; Kita-Azumi-gun Nagano
| | - Masaki Yoshida
- Department of Urology; National Center for Geriatrics and Gerontology; Obu Aichi
| | - Masayuki Takeda
- Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering; University of Yamanashi; Chuo Yamanashi
| | - Osamu Yokoyama
- Department of Urology, Faculty of Medical Science; University of Fukui; Yoshida-gun Fukui
| | - Yoji Morisaki
- Medicines Development Unit Japan; Eli Lilly Japan K.K.; Kobe Hyogo Japan
| | - Masahiro Murakami
- Medicines Development Unit Japan; Eli Lilly Japan K.K.; Kobe Hyogo Japan
| | - Lars Viktrup
- Lilly Research Laboratories; Eli Lilly and Company; Indianapolis Indiana USA
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Zhang LT, Park JK. Are phosphodiesterase type 5 inhibitors effective for the management of lower urinary symptoms suggestive of benign prostatic hyperplasia? World J Nephrol 2015; 4:138-147. [PMID: 25664256 PMCID: PMC4317624 DOI: 10.5527/wjn.v4.i1.138] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Revised: 07/22/2014] [Accepted: 10/10/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To review the efficacy of phosphodiesterase type 5 inhibitors (PDE5-Is) in lower urinary tract symptoms (LUTS) suggestive of benign prostate hyperplasia (LUTS/BPH).
METHODS: A comprehensive research was conducted to identify all publications relating to benign prostate hyperplasia and treatment with sildenafil, vardenafil and tadalafil. To assess the efficacy, the changes in total international prostate symptom score (IPSS), IPSS subscore including voiding, storage and quality of life (QoL), Benign prostatic hyperplasia Impact Index (BII), maximum urinary flow rate (Qmax) and the International Index of Erectile Function (IIEF) were extracted. A meta-analytical technique was used for the analysis of integrated data from the included studies to evaluate the mean difference in the results.
RESULTS: Total IPSS score, IIEF and BII showed a significant improvement in trials in which LUTS/BPH with or without erectile dysfunction (ED) were compared with the placebo. For LUTS/BPH, the mean differences of total IPSS score, IIEF and BII are -2.17, 4.88 and -0.43, P < 0.00001, respectively. For LUTS/BPH with comorbid ED, the mean difference are -1.97, 4.54 and -0.52, P < 0.00001, respectively. PDE5-Is appear to improve IPSS storage, voiding and QoL subscore (mean difference = -0.71, -1.23 and -0.33, P < 0.00001, respectively). Although four doses of tadalafil (2.5, 5, 10 and 20 mg) failed to reach significance in Qmax (mean difference = 0.22, P = 0.10), the 5 mg dose of tadalafil significantly improved the Qmax (mean difference = 0.33, P = 0.03).
CONCLUSION: PED5-Is demonstrated efficacy for improving LUTS in BPH patients with or without ED and could be considered to be the first line treatment for LUTS/BPH.
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34
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Akino H. Editorial Comment to Tadalafil 5 mg once-daily therapy for men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: Results from a randomized, double-blind, placebo-controlled trial carried out in Japan and Korea. Int J Urol 2014; 21:676. [DOI: 10.1111/iju.12422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Hironobu Akino
- Department of Urology; Faculty of Medical Science; University of Fukui; Fukui Japan
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