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Expert Opinion on Pharmacotherapy Jun 2019In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth... (Review)
Review
In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth muscle and/or reduce prostate enlargement. Areas covered: This article reviews the major preclinical and clinical data on PDE5 inhibitors with a specific focus on tadalafil. It includes details of the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) - PDE5 pathway in the LUT organs (bladder and prostate) in addition to the available data on tadalafil in patients with LUTS secondary to BPH with or without erectile dysfunction (ED). Expert opinion: Preclinical and clinical data have clearly demonstrated that PDE5 inhibitors induce bladder and prostate relaxation, which contributes to the improvement seen in storage symptoms in both animal models of bladder and prostate hypercontractility. Tadalafil is effective both as a monotherapy and add-on therapy in patients with LUTS secondary to BPH. Furthermore, as LUTS-BPH and ED are urological disorders that commonly coexist in aging men, tadalafil is more advantageous than α1-adrenoceptors and should be used as the first option. Tadalafil is a safe and tolerable therapy and unlike α1- adrenoceptors and 5-alpha reductase inhibitors, which can cause sexual dysfunctions, tadalafil improves sexual function.
Topics: 5-alpha Reductase Inhibitors; Animals; Erectile Dysfunction; Humans; Lower Urinary Tract Symptoms; Male; Phosphodiesterase 5 Inhibitors; Prostatic Hyperplasia; Sexual Dysfunction, Physiological; Tadalafil; Treatment Outcome
PubMed: 30901259
DOI: 10.1080/14656566.2019.1589452 -
International Urology and Nephrology Oct 2017Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This systematic review and meta-analysis were conducted to directly compare tadalafil with sildenafil for the treatment of ED.
METHODS
We designed a strategy for searching the PubMed, Embase, EBSCO, Web of Science and Cochrane library databases; the reference lists of the retrieved studies were also investigated. A literature review was performed to identify all published randomized or non-randomized controlled trials that compared tadalafil with sildenafil for the treatment of ED and to assess the quality of the studies. Two investigators independently and blindly screened the studies for inclusion. The meta-analysis was performed using RevMan 5.0.
RESULTS
A total of 16 trials that compared tadalafil with sildenafil for the treatment of ED were included in the meta-analysis. In the meta-analysis, tadalafil and sildenafil appeared to have similar efficacies and overall adverse event rates. However, compared with sildenafil, tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil. Additionally, the myalgia and back pain rates were higher and the flushing rate was lower with tadalafil than with sildenafil.
CONCLUSION
Tadalafil shares a similar efficacy and safety with sildenafil and significantly improves patients' sexual confidence. Furthermore, patients and their partners prefer tadalafil to sildenafil. Hence, tadalafil may be a better choice for ED treatment.
Topics: Back Pain; Controlled Clinical Trials as Topic; Erectile Dysfunction; Flushing; Humans; Male; Myalgia; Patient Preference; Phosphodiesterase 5 Inhibitors; Self Efficacy; Sildenafil Citrate; Tadalafil
PubMed: 28741090
DOI: 10.1007/s11255-017-1644-5 -
Journal of Endourology Jun 2017To assess the efficacy and safety of tadalafil in facilitating the spontaneous passage of distal ureteral stones. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and safety of tadalafil in facilitating the spontaneous passage of distal ureteral stones.
METHODS
The relevant studies were identified by searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to November 2016. Randomized controlled trials evaluating effects of tadalafil for distal ureteral stones were included.
RESULTS
Six publications involving 921 patients were included. Compared with tamsulosin monotherapy, tadalafil monotherapy or combined with tamsulosin has a significantly higher stone expulsion rate (relative risk [RR], 1.16; 95% confidence interval [CI], 1.05 to 1.29; p = 0.004; RR, 1.24; 95% CI, 1.09 to 1.42; p = 0.001, respectively) and shorter time to stone expulsion (mean difference [MD], -1.33 days; 95% CI, -2.44 to -0.23; p = 0.02; MD, -1.98 days; 95% CI, -3.08 to -0.88; p = 0.0004, respectively). Statistically significant differences were noted in pain episodes and analgesic use in favor of group tadalafil alone compared to group tamsulosin alone. The analgesic use was significantly lower in the combined group than in the tamsulosin alone group. Although the occurrence of drug-related adverse events in the tadalafil alone or combined with tamsulosin was higher than that in the use of tamsulosin-alone group, the most common adverse events were mild and tolerable.
CONCLUSIONS
Our study suggested that medical expulsive therapy for the distal ureteral stones using tadalafil alone or combined with tamsulosin is safe, efficacious, and well tolerated.
Topics: Humans; Pain Measurement; Sulfonamides; Tadalafil; Tamsulosin; Ureteral Calculi; Urological Agents
PubMed: 28384011
DOI: 10.1089/end.2016.0837 -
Urology Journal Nov 2021The purpose of this study was to compare the effectiveness of Dapoxetine, and Paroxetine as well as Dapoxetine/Tadalafil and Paroxetine/Tadalafil combinational... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The purpose of this study was to compare the effectiveness of Dapoxetine, and Paroxetine as well as Dapoxetine/Tadalafil and Paroxetine/Tadalafil combinational therapies, for the treatment of patients with premature ejaculation.
MATERIALS AND METHODS
In this clinical trial study, 120 patients with premature ejaculation were randomly divided into 4 groups: The first group was treated with Paroxetine (Pa), while the second group received Dapoxetine(Da). The third group received Paroxetine combined with Tadalafil(PT) whereas the fourth group's treatment involved the use of Dapoxetine and Tadalafil(DT) for one month. In the next 2 and 4 weeks, the cases were evaluated in terms of ejaculation duration, frequency of intercourse per week, and drug side effects.
RESULTS
The mean age of the Da, Pa, PT, DT groups was 32 ± 6.9, 32.4 ± 7.2, 31.6 ± 1.9, and 32.9 ± 7.7 years, respectively. There was a significant difference between the Da and DT groups (p = .029) in the ejaculation latency in the 4-week follow-up. In the two weeks follow-up, a significant difference was observed between DA and DT (p = 0.043), Pa and PT (p = 0.006), and Pa and DT groups (p = 0.004) in terms of ejaculation latency. Four weeks after the intervention, a significant difference was detected in the intercourse frequency of Da and PT groups (p =0.033), Pa and PT groups (p = 0.043), Pa and DT groups (p = 0.02), and Da and DT groups (p = 0.016).
CONCLUSION
Combination therapy (Tadalafil plus Paroxetine or Dapoxetine) was more effective in IELT (Intra ejaculation latency time) than mono-therapy especially in younger patients despite its slightly more side effects.
Topics: Benzylamines; Ejaculation; Humans; Male; Naphthalenes; Paroxetine; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors; Tadalafil; Treatment Outcome
PubMed: 34773634
DOI: 10.22037/uj.v18i.6644 -
Journal of the American College of... Jan 2024Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial hypertension (PAH) patients. A fixed-dose combination of the ERA macitentan and PDE5i tadalafil (M/T FDC) in a once-daily, single tablet would simplify treatment.
OBJECTIVES
The multicenter, double-blind, adaptive phase 3 A DUE study investigated the efficacy and safety of M/T FDC vs macitentan 10 mg and vs tadalafil 40 mg monotherapies in PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapy-treated patients.
METHODS
World Health Organization functional class II-III patients were randomized to M/T FDC, macitentan, or tadalafil depending on their PAH treatment (treatment-naïve, ERA, or PDE5i monotherapy) at baseline. The primary endpoint was change in pulmonary vascular resistance (PVR) at week 16.
RESULTS
In total, 187 patients were randomized to single-tablet M/T FDC (n = 108), macitentan (n = 35), or tadalafil (n = 44). PVR reduction with M/T FDC was significantly greater vs macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P < 0.0001) and vs tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P < 0.0001). Three patients died in the M/T FDC arm (judged unrelated to treatment). Adverse events (AEs) leading to discontinuation, serious AEs, and those of special interest (anemia, hypotension, and edema) were more frequent with M/T FDC.
CONCLUSIONS
Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693).
Topics: Humans; Pulmonary Arterial Hypertension; Tadalafil; Combined Modality Therapy; Phosphodiesterase 5 Inhibitors; Endothelin Receptor Antagonists; Tablets; Pyrimidines; Sulfonamides
PubMed: 38267108
DOI: 10.1016/j.jacc.2023.10.045 -
International Journal of Molecular... Apr 2022Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate... (Review)
Review
Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH) -associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout the human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity and cytochrome P19a1 (Cyp19a1) and estrogen receptor β (ERβ) expression in different in vitro systems, such as adipose, bone and prostate cancer cells, where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review, we summarize basic research and translational results applicable to the use of tadalafil in the treatment of obesity, bone loss and prostate cancer.
Topics: Animals; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Hormones; Humans; Male; Phosphodiesterase 5 Inhibitors; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Steroids; Tadalafil; Treatment Outcome
PubMed: 35457011
DOI: 10.3390/ijms23084191 -
Lower Urinary Tract Symptoms Jan 2018We 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Erectile Dysfunction; Humans; Lower Urinary Tract Symptoms; Male; Phosphodiesterase 5 Inhibitors; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Severity of Illness Index; Tadalafil
PubMed: 29341503
DOI: 10.1111/luts.12144 -
Acta Medica Indonesiana Jul 2019Tadalafil is a PDE5I which has been licensed for the treatment of erectile dysfunction (ED) since 2003, is effective from 30 minutes after administration and its... (Review)
Review
BACKGROUND
Tadalafil is a PDE5I which has been licensed for the treatment of erectile dysfunction (ED) since 2003, is effective from 30 minutes after administration and its efficacy is maintained for up to 36 hours. More recently, it is also given OAD in a lower dose to allow spontaneous sexual activities. However, whether OAD administration is more effective than PRN administration in improving the EF is yet to be established. This study aimed to evaluate whether OAD administration of tadalafil leads to a better improvement of erectile function (EF) in patients with erectile dysfunction (ED) compared to PRN administration.
METHODS
literature search of electronic database was performed through Medline, Scopus, Cochrane Library, and CINAHL databases. Cochrane Risk of Bias Tool was then employed to assess the risk of bias in each study.
RESULTS
initial literature search resulted in 231 hits, but only four studies were included in final selection. Based on our judgements, the study by Kang et al. was the most applicable in our clinical setting. This study showed that subjects who received tadalafil OAD had statistically significant higher increases of mean IIEF-EF (6.5 (SD 4.5) vs 4.9 (SD 4.2), p=0.032), proportion of "yes" responses to SEP-2 (81.8% vs 64.7%, p=0.025), and proportion of "yes" responses to SEP-3 (77.3% vs 60.3%, p=0.034).
CONCLUSION
administration of tadalafil OAD leads to a better improvement of EF compared to PRN administration.
Topics: Erectile Dysfunction; Humans; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Randomized Controlled Trials as Topic; Tadalafil; Treatment Outcome
PubMed: 31699953
DOI: No ID Found -
Andrologia Oct 2022This study aimed to investigate the protective effect of tadalafil on reactive oxygen species induced by a hyperoxia model in rats, both in terms of enzymes such as...
This study aimed to investigate the protective effect of tadalafil on reactive oxygen species induced by a hyperoxia model in rats, both in terms of enzymes such as superoxide dismutase (SOD) and nitric oxide (NO), and its pathological effects on the corpus cavernosum. Overall, 24 rats were divided into three groups. The control group (eight rats) was not exposed to any intervention. The second group (eight rats), was exposed to hyperoxia in a hyperoxia cabinet for 8 h a day for 10 days. The third group (eight rats) was exposed to hyperoxia the same as in the second group, tadalafil at a dose of 10 mg/kg was given orally as a dissolved form in water in the amount of 10-12 ml/100 g/day to the rats placed in separate cages having removed from the hyperoxia cabin. SOD levels differ enough to create a difference, but there was no significant difference in terms of NO levels. The SOD level was highest in hyperoxia conditions and lowest in the group given tadalafil. While corpus cavernosum hyperemia was found to be higher statistically in the experimental groups than in the control group, we found that the severity of hyperemia was less in the group given tadalafil. The corpus cavernosum was found to be statistically more dilated in the experimental groups than in the control group. We determined that hyperoxia status increased the level of SOD and this level decreased with tadalafil administration, which would make a statistical difference.
Topics: Animals; Hyperemia; Hyperoxia; Nitric Oxide; Oxidative Stress; Rats; Superoxide Dismutase; Tadalafil
PubMed: 35676072
DOI: 10.1111/and.14494 -
Alzheimer's & Dementia : the Journal of... Dec 2022There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI.
METHODS
In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling.
RESULTS
Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (-7.8, -4.9 mmHg; P < .001). No serious adverse events were observed.
DISCUSSION
This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.
Topics: Humans; Aged; Tadalafil; Cognitive Dysfunction; Double-Blind Method
PubMed: 35135037
DOI: 10.1002/alz.12559