Agent for premature ejaculation shows no interactions with PDE-5 inhibitors

This study aimed to compare the pharmacological effect assessed by IELT in men suffering from PE by using either dapoxetine alone, tadalafil alone, or their combination as a primary outcome and to evaluate the possible side effects of drug therapy as a secondary outcome.

See also

PE is defined according to the International Society for Sexual Medicine (ISSM) guidelines as ejaculation that always happens in fewer than 1 minute following vaginal penetrating from the initial sexual encounter (lifelong PE), or a decrease in IELT, less than 3 min (acquired PE) with inability to delay ejaculation on all or nearly all vaginal penetrations and negative personal consequences, such as distress, frustration, bother and/or avoidance of sexual intimacy [Citation2]. Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) define PE as a persistent or recurrent ejaculation that occurs within approximately 1 minute after vaginal penetration and before the individual wishes it. The problem must present for at least 6 months and present on almost all (approximately 75–100%) or on all occasions of sexual attempts with clinically significant distress and cannot be explained by a nonsexual mental disorder or as a result of severe relationship distress and is not attributable to the effects of a substance/medication or other medical condition [Citation3,Citation4]. A recent comprehensive novel classification of PE was reported by Raveendran A. In this classification, the grading of the severity of reduction of IELT was reported as mild or grade 1 (IELT of 2 to 3 minutes), moderate or grade 2 (IELT of 1 to less than 2 minutes), severe or grade 3 (IELT less than 1 minute), and extreme or grade 4 (ejaculation occurring prior to vaginal penetration) [Citation5].

How sildenafil is used

Premature ejaculation is a frequent male sexual dysfunction, although the real incidence is unclear, 24% to 30% of males may be affected [Citation6,Citation7]. Several drugs as tricyclic antidepressants (e.g. clomipramine) and tramadol could be used for treatment of PE. Selective serotonin-reuptake-inhibitors (SSRIs), like escitalopram, fluoxetine, serteralin, paroxetine and dapoxetine are the most common medications used for management of PE [Citation8–10]. As SSRI, dapoxetine was the first licenced drug with FDA approval used for on-demand management of PE. This was a prospective, randomized work of patients who attended our andrology clinic with PE from May 2021 to September 2022.

Patients were randomly allocated into three groups (using a block randomization strategy in Stata, version 13.1, Stata Corp, for Microsoft windows). Participants in group (A) received on- demand tadalafil 5 mg two hours before intercourse; Participants in group (B) received on- demand dapoxetin 30 mg two hours before intercourse; and Participants in group (C) received an on-demand combination of both tadalafil 5 mg and dapoxetin 30 mg two hours before intercourse.

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Dapoxetin acts by neglecting the effect for the different G protein coupled and ligand gated channels for all 5-hydroxytryptamin (5-HT) receptor subtypes, it inhibits the 5-HT transporter and activate the 5-HT 2C receptor, an action which diminishes the operation of 5-HT 1A receptor, thus reattaining equilibrium between the actions of 5-HT 1A and 5-HT 2C receptors and this leads to increased 5-HT levels in the synaptic clefts which results in delayed ejaculation [Citation11]. Nitric oxide (NO) activates guanylate cyclase which increases the intracellular cGMP in the corpus cavernosum causing smooth muscle relaxation. PDE-5 inhibitors act through increasing nitric oxide which causes relaxation of the smooth muscles of corpus cavernosum and the vas deferens and seminal-vesicles, also they reduce anxiety from sexual performance which is commonly associated with PE [Citation12]. According to several researches, using SSRIs and PDE-5 inhibitors together enhances sexual pleasure and boosts IELT when compared with taking SSRIs alone. PDE-5 may suppress the central sympathetic tone, which causes better erection and increased the time interval for ejaculation [Citation13]. Each participant was instructed to engage in sexual activity 2–3 times per week.

• Sildenafil does not protect against sexually transmitted infections.
• Dapoxetine does not reduce the frequency of ejaculation but delays it.
• Patients on nitrate therapy should avoid sildenafil due to severe hypotension risk.
• Dapoxetine is often used in combination with behavioral therapy for PE.
• Sildenafil may interact with medications for HIV and other conditions.
• Dapoxetine’s safety profile is well-established for short-term use.
• Both medications should be stored safely away from children.
• Sildenafil can sometimes cause priapism, which requires emergency treatment.
• Dapoxetine should be discontinued if adverse effects are intolerable.
• Combining sildenafil with alcohol can worsen hypotensive side effects.
• Dapoxetine may also cause dry mouth and blurred vision in some users.
• Regular medical check-ups are recommended during long-term use of these drugs.

If an individual met the International Society for Sexual Medicine’s requirements which describes PE as ejaculation that always happens within a minute, following vaginal penetration during the initial sexual encounter (lifetime PE),

Regulatory history

In a single-center, single-arm, open-label clinical study, 74 patients with lifelong / acquired PE and ED were included between October 2016 to September 2017.Patients received on demand dapoxetine / sildenafil (30/50 mg film-coated tablets) 1-3 hours before sexual intercourse for 4 weeks (2 days a week and no more than once a day). All patients were instructed to record their intravaginal ejaculatory latency time (IELT). They were also instructed to complete Premature Ejaculation Diagnostic The study was completed with 53 patients (71.62%). Mean age of the patients was 45.32±10.05. Before the treatment, geometric mean IELT of the patients was 22.72±15.16 seconds, mean PEDT score was 16.85±2.42, mean PEP score was 3.36±1.12and IIEF-EF score was 13.17±3.33.

Product Sucralfate 500mg+Domperidone 10mg+Simethicone 25mg

At the end of the 4-week treatment period, statistically significant improvements were observed in the mean IELTs, PEP and IIEF-EF scores compared to the patients' pre-treatment values (69.47±103.34;p<0.001, 9.92±2.36;p<0.001, The dapoxetine/ sildenafil combination therapy significantly improves the IELT values and patient reported outcome measures of PE patients who also suffer from ED. Although several side effects were reported, these were mild and reversible. To compare the efficacy of tadalafil alone, dapoxetine alone, and tadalafil with dapoxetine as a combination therapy for the treatment of premature ejaculation. Eligible patients attended our andrology clinic with premature ejaculation were tab dapoxetine 30 mg randomly allocated into three groups: group A (92 participants) received on-demand tadalafil, 5 mg; group B (91 participants) were given on-demand dapoxetine, 30 mg; and group C (89 participants) received on-demand combination of tadalafil, 5 mg, and dapoxetine, 30 mg. We assessed the changes in the intravaginal ejaculatory latency time (IELT) and the satisfaction scores 1, 2, and 3 months after treatment.

Mechanism of action

Highly statistically significant improvements were found in the mean IELT and satisfaction scores 1, 2, and 3 months post-treatment in all groups (P = <0.001). Post hoc analysis suggested this improvement was more pronounced in group C (P < 0.001). Both tadalafil and dapoxetine are effective in the treatment of patients with premature ejaculation, but the combination of both drugs gives better results. Premature ejaculation (PE) is a male sexual disorder characterized by a brief intra-vaginal ejaculatory latency time (IELT) and lack of ability to properly control ejaculation which has detrimental personal effects [Citation1]. There is no global definition for PE. or a substantial decline in IELT, often within less than 3 minutes (acquired PE), with detrimental personal effects, including anxiety, annoyance, and/or avoiding of sexual intimacy, PE was assumed to be present.

• Sildenafil is also used in treating certain cases of high blood pressure in lungs.
• Dapoxetine’s primary goal is to delay ejaculation, increasing sexual confidence.
• Both drugs are typically prescribed after clinical assessment of sexual health issues.
• Proper storage of sildenafil and dapoxetine involves keeping away from moisture and heat.
• Sildenafil can cause visual disturbances as a rare side effect.
• Dapoxetine may sometimes lead to mood changes or irritability.
• Both medications are contraindicated with recreational drugs for safety.
• Sildenafil requires careful dose titration for optimal effectiveness.
• Dapoxetine’s use is generally limited to short-term management of PE.
• Patients should report any side effects such as chest pain or severe dizziness.
• Sildenafil’s absorption can be affected by high-fat meals, delaying effects.
• Dapoxetine should be ingested with water, on an empty stomach if possible.

All patients were evaluated by filling a detailed documented medical history including the International Index of Erectile Function (IIEF) 5- items questionnaires to exclude those with erectile-dysfunction [Citation14].

Limitations of the study

Consumers should exercise caution before purchasing any product in the above categories. Please refer to the links below for more information: Department of Pharmaceutical Analysis, Grace College of Pharmacy, Kodunthirapully, Palakkad, India. Abstract: Two simple UV-Spectrophotometric methods have been developed for simultaneous determination of sildenafil citrate and dapoxetine HCl in pharmaceutical formulation. For both the methods stock solutions were prepared in methanol followed by the further required dilutions with methanol. Proposed Vierodt’s method and double point standardization method, the max for the estimation of sildenafil citrate and dapoxetine HCl were selected at 292nm and 231nm respectively.

Warnings for people with certain health conditions

In both methods, the linearity range lies between 2-20 µg/mL for sildenafil citrate and 1.2-12 µg/mL for dapoxetine HCl at their respective wavelengths. By Vierodt’s method the percentage of sildenafil citrate and dapoxetineHCl was found to be 99.25%, dapoxetine HCl 99.08% respectively. It was estimated to be 98.1% for sildenafil Citrate and 99.16% for Ddapoxetine HCl by double point standardization method. Both these methods were found to be accurate, precise, stable and robust as indicated by low values of % RSD. Thus the present study gives excellent method for the determination of both the drugs in combined tablet formulation.

Patients and Methods

If you are interested in supporting our work and would like to contribute, you are welcome to mail me at [email protected] or at [email protected] it will be a great help and will surely be appreciated. 058 The Efficacy and Safety of Dapoxetine / Sildenafil Combination Therapy in the Treatment of Men with Premature Ejaculation and Erectile Dysfunction – DAP-SPEED Study - ScienceDirect Please enable JavaScript to use all the features on this page. 058 The Efficacy and Safety of Dapoxetine / Sildenafil Combination Therapy in the Treatment of Men with Premature Ejaculation and Erectile Dysfunction – DAP-SPEED Study Author links open overlay panelM.Tuken1, M.G.Culha2, E.C.Serefoglu3 Premature ejaculation (PE) and erectile dysfunction (ED) are the most prevalent sexual disorders in men. ED is commonly reported among patients with PE.Although recent guidelines recommend to treat ED first in men with both PE and ED, this recommendation is not based on evidence and there is limited data about the efficacy and safety of dapoxetin / sildenafil combination therapy for these patients. The aim of this study is to evaluate the clinical efficacy and safety of the dapoxetine / sildenafil combination (Dapoxil 30/50 mg film-coated tablet) in the treatment of patients with PE and concomitant ED.