https://doi.org/10.4081/aiua.2025.14117
Efficacy and safety of on-demand dapoxetine combined with phosphodiesterase-5 inhibitor compared to monotherapy dapoxetine as a treatment of premature ejaculation without erectile dysfunction: a systematic review and meta-analysis
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Published: 30 September 2025
Background: Premature ejaculation (PE) affects about 30% of the male population. The European Association of Urology (EAU) guidelines state that monotherapy dapoxetine on-demand has been successfully used to treat PE throughout Europe. Several studies have stated that when dapoxetine and phosphodiesterase-5 inhibitor (PDE-5i) are used combined, sexual enjoyment and intravaginal ejaculation latency time (IELT) are increased more than when dapoxetine is taken alone. However, further investigation is needed to determine whether PDE-5i and dapoxetine can be safely consumed together.
Methods: This study was conducted using 5 randomized controlled trials (RCTs), which systematically extracted from online databases, namely Science Direct, PubMed, Google Schoolar and Cochrane Library. Included studies were assessed using Cochrane Risk of Bias (RoB) 2.0 for RCTs. The data analysis was performed using RevMan software 5.1 of the Cochrane Collaboration.
Results: Five RCTs with a total of 498 potent men with PE from the period 2013-2024 showed pooled mean difference of dapoxetine + PDE-5i was found significantly associated with higher post-treatment IELT scores compared to monotherapy dapoxetine (MD 1.08; 95% CI 0.34-1.83; p=0.004; I2 = 95%; 4 RCTs). The pooled mean difference of dapoxetine + PDE-5i also showed statistically significant association with higher post-treatment sexual satisfaction scale (SSS) scores compared to monotherapy dapoxetine (MD 0.76; 95% CI 0.49-1.04; p<0.00001; I2 = 68%; 2 RCTs). Among 10 adverse effects (headacahe, flushing, nausea, dizziness, fatigue, nasal congestion, palpitation, vomitting, sleep disturbance, and constipation), the use of combination therapy is presenting significantly higher incidence of headache, flushing, nasal congestion compared to monotherapy dapoxetine (RR 3.00; 95% CI: 1.91-4.71; p<0.00001; I2: 0%; 5 RCTs), (RR 15.78; 95% CI: 5.48-45.45; p<0.00001; I2: 24%; 5 RCTs), (RR 9.00; 95% CI: 1.17-69.01; p=0.03; I2: 0%; 2 RCTs), respectively.
Conclusions: This study demonstrates that the combination of dapoxetine and PDE-5i significantly improves post-treatment scores of IELT and sexual satisfaction compared to dapoxetine monotherapy. Despite an increased risk of certain side effects, the overall tolerability of the combination therapy remains favorable.
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