Dapoxetine “On-Demand” for Premature Ejaculation: What Guidelines Say, What’s New, and What Are the Real Risks?

Men with both premature ejaculation (PE) and erectile dysfunction (ED) experience lower quality of life than men with either PE or ED alone. Presented at the World Congress of Sexology, July 10–15, 2005, Montreal, Canada. FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug–drug interactions: impact on labeling. Design and Analysis of Bioavailability and Bioequivalence Studies.

Can dapoxetine (Priligy) be used at any age?

The use of topical anesthetics is a relatively efficacious, user friendly, and inexpensive modality for PE treatment (48). However, they can cause penile glans numbness and condom use or prior washing off before sexual activity is required to prevent transference of the drug to the vaginal mucosa (14). Another potential medical treatment option for PE is the phosphodiesterase type 5 (PDE-5) inhibitors. FDA/Center for Drug Evaluation and Research (CDER). Guidance for Industry: In Vivo Drug Metabolism/Drug Interaction Studies-Study Design, Data Analysis, and Recommendations for Dosing and Labeling. Review of tadalafil in the treatment of erectile dysfunction. Expert Opin Pharmacother 2003; 4: 2049–2056. New phosphodiesterase inhibitors in the treatment of erectile dysfunction. Expert Opin Pharmacother 2004; 5: 2241–2249. Note for guidance on the investigation of drug interactions (CPMP/EWP/560/95). Pharmacokinetic–pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Ring BJ, Patterson BE, Mitchell MI, Vandenbranden M, Gillespie J, Bedding AW et al. Effect of tadalafil on cytochrome P450 3A4-mediated clearance: studies in vitro and in vivo. The conduct of in vitro and in vivo drug–drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. This work was supported by ALZA Corporation. Redefining a sexual medicine paradigm: subclinical premature ejaculation as a new taxonomic entity Nature Reviews Urology (2021) Efficacy and safety of dapoxetine/sildenafil combination tablets in the treatment of men with premature ejaculation and concomitant erectile dysfunction—DAP-SPEED Study International Journal of Impotence Research (2019) Derivative Synchronous Fluorescence Spectroscopy for the Simultaneous Determination of Dapoxetine Hydrochloride and Vardenafil in Binary Mixtures Journal of Applied Spectroscopy (2014) Current Diagnosis and Management of Premature Ejaculation Current Sexual Health Reports (2014) New insights on premature ejaculation: a review of definition, classification, prevalence and treatment Asian Journal of Andrology (2012) Rapid or premature ejaculation (PE) was first described in the medical literature in 1887 (1) and is widely accepted to be the most common sexual complaint in males (2).

• It's essential to follow the prescribed dosage to prevent side effects.
• Dapoxetine is a prescription medication, so consultation is necessary.
• Combining dapoxetine with certain antidepressants may increase serotonin syndrome risk.
• The drug is considered effective for many men but may not work for all.
• Using dapoxetine can enhance relationships impacted by premature ejaculation.
• Regular medical check-ups are recommended during treatment.

Among the multiple definitions and criteria for the diagnosis of PE, the most frequently cited are short time to ejaculation, inability to delay or control ejaculation and negative personal consequences (3-6). PE can be subdivided into lifelong and acquired PE (7). Lifelong PE is defined by the International Society of Sexual Medicine (ISSM) as a male sexual dysfunction characterized by ejaculation that always or nearly always occurs before or within approximately one minute of vaginal penetration, the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences such as distress, bother, frustration and/or the avoidance of sexual intimacy (6).

Product	Dosage	Quantity + Bonus	Price
Tadalista Super Active	20mg	10 Pills	55.64€ 52.99€	Buy
Priligy Generic Dapoxetine	60mg	60 + 8 Pills	183.06€ 174.34€	Buy
Levitra Soft Tabs	20mg	270 + 10 Pills	521.78€ 496.93€	Buy
Priligy Generic Dapoxetine	60mg	180 + 10 Pills	494.76€ 471.20€	Buy
Priligy Generic Dapoxetine	60mg	30 + 6 Pills	106.65€ 101.57€	Buy
Priligy Generic Dapoxetine	60mg	10 Pills	47.63€ 45.36€	Buy
Viagra Soft Tabs	100mg	60 + 6 Pills	152.94€ 145.66€	Buy
Priligy Generic Dapoxetine	60mg	20 + 4 Pills	77.31€ 73.63€	Buy
Priligy Generic Dapoxetine	60mg	120 + 10 Pills	341.26€ 325.01€	Buy
Priligy Generic Dapoxetine	60mg	90 + 10 Pills	265.64€ 252.99€	Buy
Levitra Original	20mg	8 Pills	65.05€ 61.95€	Buy

This definition is based on evidence that 80-90% of men with lifelong PE ejaculate within 60 seconds (8). Acquired PE characteristically develops later in life after a history of normal sexual function and ejaculatory control (9). Acquired PE is usually associated with urologic or psychological problems (10). This form of PE can often be remedied by treating the underlying etiology (10). In 2006, two more PE subtypes, natural variable PE and premature-like ejaculatory dysfunction, were proposed (11).

More info about Priligy

Inherited defects in serotonergic control have been proposed to underlie a genetic basis of PE, possibly due to hyposensitive 5-HT2C and/or hypersensitive 5-HT1A receptors or increased expression of the serotonin transporter (1,18,19). Acquired neurological diseases such as multiple sclerosis, peripheral neuropathies, spinal cord tumors, and a hypothetical hypersensitivity of the glans penis have been associated with PE; however, much of this evidence is limited and conflicting (20). Possible pharmacological causes of PE include bupropion intake and withdrawal of opioid/SSRI drug use (21-23). Urological factors include a short frenula, with one study reporting 43% of its lifetime PE patients having short frenula and improvement with frenulectomy (24). Researchers have linked hyperthyroidism to PE (25-28).

Acquired PE

As many as 72% of untreated hyperthyroid men were found to have PE according to one study and the mean IELTs increased dramatically after treatment (28). Some studies have noted a strong association between chronic prostatitis and PE. Improvements in PE and IELTs following antimicrobial therapy were reported (29-32). PE is strongly associated with psychosocial factors such as immature techniques for controlling ejaculation, conditioning from early hurried sexual experiences, alexithymia, anxiety, social phobias, and distressed emotions (33-36). Conversely, men with psychosocial burden have often leads to PE, leading to the question of which came first and making it difficult to scientifically establish causality (20).

Clinical studies of dapoxetine

There are multiple psychological/behavioral treatments for PE, which may be used as a single therapy for natural variable PE or premature-like ejaculatory dysfunction or in combination with pharmacologic therapy for other subtypes of PE (10,37). Psychotherapy and sexual education can reduce patient anxiety, increase communication between a man and his partner, give patients more confidence, and modify many maladaptive sexual scripts (10,14,38). Behavioral therapy is primarily comprised of the “stop and start” technique, established by Semans (39) and a variation/modification of this technique, the ‘squeeze’ technique, proposed by Masters and Johnson (40). The aim of these methodologies is to help a patient maintain his sexual excitement just below the threshold for triggering ejaculation, by either stopping sexual activity or squeezing the head of the penis until the urge to ejaculate subsides (41). Desensitization of the penis via masturbation before sexual intercourse is a practice used by younger men and has proved effective in prolonging the ejaculatory period (42). Natural variable PE is regarded as a normal variant of sexual performance, whereas premature-like ejaculatory dysfunction is defined as a complaint of PE superimposed on ejaculation time in the normal range (10). These new subtypes help physicians more precisely stratify patients and set treatment algorithms.

Aspect	Details
Drug Class	Selective Serotonin Reuptake Inhibitor (SSRI)
Mechanism of Action	Increases serotonin levels in the nervous system, delaying ejaculation
Half-Life	Approximately 19 hours
Metabolism	Liver (via CYP enzymes)
Excretion	Primarily in urine
Interaction Potential	May interact with other serotonergic drugs

Pharmacotherapy remains the basis of management of lifelong and acquired PE, whereas psychotherapy should be considered for patients with natural variable PE and premature like ejaculatory dysfunction (12). Ejaculation is comprised of two phases: emission and expulsion (13). The ejaculatory reflex requires the coordination of sympathetic, parasympathetic and somatic pathways, interlaced with central serotonergic and dopaminergic neuronal pathways (5,13). Emission is the deposition of sperm and seminal fluid into the posterior urethra by contraction of the seminal vesicles and the prostate gland and is mediated by the sympathetic nervous system (T10-L2) (13,14).

• Summary: a targeted on-demand treatment for premature ejaculation.
• Requires professional diagnosis and prescription for safe use.
• Most side effects are mild and manageable.
• Serious risks include serotonin syndrome and syncope.
• Improves ejaculatory control and sexual satisfaction.
• Part of a holistic management strategy.
• Patient education on expectations and safety is paramount.
• Regular medical follow-up ensures optimal and safe use.

The epididymis, vas deferens, seminal vesicles, prostate gland, prostatic urethra as well as the bladder neck are involved in the emission phase (13).

What are the possible side effects of taking Priligy?

This work was supported by ALZA Corporation. Redefining a sexual medicine paradigm: subclinical premature ejaculation as a new taxonomic entity Nature Reviews Urology (2021) Efficacy and safety of dapoxetine/sildenafil combination tablets in the treatment of men with premature ejaculation and concomitant erectile dysfunction—DAP-SPEED Study International Journal of Impotence Research (2019) Derivative Synchronous Fluorescence Spectroscopy for the Simultaneous Determination of Dapoxetine Hydrochloride and Vardenafil in Binary Mixtures Journal of Applied Spectroscopy (2014) Current Diagnosis and Management of Premature Ejaculation Current Sexual Health Reports (2014) New insights on premature ejaculation: a review of definition, classification, prevalence and treatment Asian Journal of Andrology (2012) Rapid or premature ejaculation (PE) was first described in the medical literature in 1887 (1) and is widely accepted to be the most common sexual complaint in males (2). Among the multiple definitions and criteria for the diagnosis of PE, the most frequently cited are short time to ejaculation, inability to delay or control ejaculation and negative personal consequences (3-6). PE can be subdivided into lifelong and acquired PE (7). Lifelong PE is defined by the International Society of Sexual Medicine (ISSM) as a male sexual dysfunction characterized by ejaculation that always or nearly always occurs before or within approximately one minute of vaginal penetration, the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences such as distress, bother, frustration and/or the avoidance of sexual intimacy (6).

Development of this evidence summary

This definition is based on evidence that 80-90% of men with lifelong PE ejaculate within 60 seconds (8). Acquired PE characteristically develops later in life after a history of normal sexual function and ejaculatory control (9). Acquired PE is usually associated with urologic or psychological problems (10). This form of PE can often be remedied by treating the underlying etiology (10). In 2006, two more PE subtypes, natural variable PE and premature-like ejaculatory dysfunction, were proposed (11).

Related Salt

Natural variable PE is regarded as a normal variant of sexual performance, whereas premature-like ejaculatory dysfunction is defined as a complaint of PE superimposed on ejaculation time in the normal range (10). These new subtypes help physicians more precisely stratify patients and set treatment algorithms. Pharmacotherapy remains the basis of management of lifelong and acquired PE, whereas psychotherapy should be considered for patients with natural variable PE and premature like ejaculatory dysfunction (12). Ejaculation is comprised of two phases: emission and expulsion (13). The ejaculatory reflex requires the coordination of sympathetic, parasympathetic and somatic pathways, interlaced with central serotonergic and dopaminergic neuronal pathways (5,13). Expulsion is the forceful antegrade ejection of sperm from the urethra and is controlled by somatic nerves (S2-4) (14).

• Combining dapoxetine with recreational drugs can be dangerous and is not recommended.
• Dapoxetine can improve quality of life in men with PE.
• Always consult a healthcare provider before starting or stopping medication.
• Maintain open communication with your partner about treatment options.
• Lifestyle adjustments, like reducing stress, can complement medication treatment.
• Regular health screenings are advised during dapoxetine therapy.

The external urethral sphincter relaxes and the ischiocavernosus, bulbocavernosus and other pelvic floor muscle undergo rhythmic synchronous contractions to allow antegrade flow of sperm out of the urethra. Concurrently, the smooth muscle of the bladder neck contracts to prevent retrograde flow (13). A large body of research indicates that serotonin acting on the brain’s post-synaptic receptors exerts an overall inhibitory control on the ejaculatory process.

Safety Assessments

These psychological/behavioral practices can lead to short-term improvement with overall success rates of 50-60% (43,44). However, as these methods require patient/partner commitment and practice to maintain viability, their efficacy decreases over time (45). Topical local anesthetics such as lidocaine and/or prilocaine are the oldest drugs used for PE treatment. These are available in cream, gel and aerosol formulations (46,47). These agents delay ejaculation in theory by reducing the sensitivity of the glans penis. As far back as 1976, administration of the serotonin (5-Hydroxytryptamine, 5-HT) precursor 5-Hydroxytryptophan was shown to inhibit male rat sexual behavior (15). 5-HT1A receptors have been demonstrated to exert a pro-ejaculatory effect on male sexual behavior. These receptors act on serotonergic neuronal cell bodies as a means dapoxetine 60 mg tablets of down regulating the release of 5-HT into the synaptic cleft. Hence, microinjections and a systemic delivery of 8-hydroxy-2-(di-n-propyl-amino) tetralin hydrobromide (8-OH-DPAT), a selective agonist of 5-HT1A receptors, elicits a diminished ejaculatory latency time in rats. There is limited evidence on the function of 5-HT1B and 5-HT2C receptors on ejaculation; however, the studies conducted implicate inhibitory activity for 5-HT1B and 5-HT2C (16,17). Both 5-HT2C and 5-HT1B receptors are distributed within the hypothalamus and in the lumbosacral areas of the spinal cord, along with 5-HT1A receptors (18). The etiology of PE is multi-factorial in nature. Clinical evidence is limited and contradictory for many purported mechanisms. PE has been associated with both inherited and non-inherited neurobiological etiologies, pharmacological factors, urological pathology, endocrine disorders, and psychological/psychosocial mechanisms.

Counseling and Sex Therapy

Inherited defects in serotonergic control have been proposed to underlie a genetic basis of PE, possibly due to hyposensitive 5-HT2C and/or hypersensitive 5-HT1A receptors or increased expression of the serotonin transporter (1,18,19). Acquired neurological diseases such as multiple sclerosis, peripheral neuropathies, spinal cord tumors, and a hypothetical hypersensitivity of the glans penis have been associated with PE; however, much of this evidence is limited and conflicting (20). Possible pharmacological causes of PE include bupropion intake and withdrawal of opioid/SSRI drug use (21-23). Urological factors include a short frenula, with one study reporting 43% of its lifetime PE patients having short frenula and improvement with frenulectomy (24). Researchers have linked hyperthyroidism to PE (25-28).

INFORMATION ABOUT DAPOXETINE

Men with both premature ejaculation (PE) and erectile dysfunction (ED) experience lower quality of life than men with either PE or ED alone. Presented at the World Congress of Sexology, July 10–15, 2005, Montreal, Canada. FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug–drug interactions: impact on labeling. Design and Analysis of Bioavailability and Bioequivalence Studies. FDA/Center for Drug Evaluation and Research (CDER).

Is Dapoxetine Safe?

Guidance for Industry: In Vivo Drug Metabolism/Drug Interaction Studies-Study Design, Data Analysis, and Recommendations for Dosing and Labeling. Review of tadalafil in the treatment of erectile dysfunction. Expert Opin Pharmacother 2003; 4: 2049–2056. New phosphodiesterase inhibitors in the treatment of erectile dysfunction. Expert Opin Pharmacother 2004; 5: 2241–2249.

Step 4 — Follow-Up and Ongoing Support

Note for guidance on the investigation of drug interactions (CPMP/EWP/560/95). Pharmacokinetic–pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Ring BJ, Patterson BE, Mitchell MI, Vandenbranden M, Gillespie J, Bedding AW et al. Effect of tadalafil on cytochrome P450 3A4-mediated clearance: studies in vitro and in vivo. The conduct of in vitro and in vivo drug–drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. As many as 72% of untreated hyperthyroid men were found to have PE according to one study and the mean IELTs increased dramatically after treatment (28). Some studies have noted a strong association between chronic prostatitis and PE. Improvements in PE and IELTs following antimicrobial therapy were reported (29-32).

How does dapoxetine (Priligy) work?

Emission is the deposition of sperm and seminal fluid into the posterior urethra by contraction of the seminal vesicles and the prostate gland and is mediated by the sympathetic nervous system (T10-L2) (13,14). The epididymis, vas deferens, seminal vesicles, prostate gland, prostatic urethra as well as the bladder neck are involved in the emission phase (13). Expulsion is the forceful antegrade ejection of sperm from the urethra and is controlled by somatic nerves (S2-4) (14). The external urethral sphincter relaxes and the ischiocavernosus, bulbocavernosus and other pelvic floor muscle undergo rhythmic synchronous contractions to allow antegrade flow of sperm out of the urethra. Concurrently, the smooth muscle of the bladder neck contracts to prevent retrograde flow (13).

Patient-reported global impression of change (PGIC)

A large body of research indicates that serotonin acting on the brain’s post-synaptic receptors exerts an overall inhibitory control on the ejaculatory process. As far back as 1976, administration of the serotonin (5-Hydroxytryptamine, 5-HT) precursor 5-Hydroxytryptophan was shown to inhibit male rat sexual behavior (15). 5-HT1A receptors have been demonstrated to exert a pro-ejaculatory effect on male sexual behavior. These receptors act on serotonergic neuronal cell bodies as a means dapoxetine 60 mg tablets of down regulating the release of 5-HT into the synaptic cleft. Hence, microinjections and a systemic delivery of 8-hydroxy-2-(di-n-propyl-amino) tetralin hydrobromide (8-OH-DPAT), a selective agonist of 5-HT1A receptors, elicits a diminished ejaculatory latency time in rats.

Step 3 — Treatment Planning

There is limited evidence on the function of 5-HT1B and 5-HT2C receptors on ejaculation; however, the studies conducted implicate inhibitory activity for 5-HT1B and 5-HT2C (16,17). Both 5-HT2C and 5-HT1B receptors are distributed within the hypothalamus and in the lumbosacral areas of the spinal cord, along with 5-HT1A receptors (18). The etiology of PE is multi-factorial in nature. Clinical evidence is limited and contradictory for many purported mechanisms. PE has been associated with both inherited and non-inherited neurobiological etiologies, pharmacological factors, urological pathology, endocrine disorders, and psychological/psychosocial mechanisms. PE is strongly associated with psychosocial factors such as immature techniques for controlling ejaculation, conditioning from early hurried sexual experiences, alexithymia, anxiety, social phobias, and distressed emotions (33-36). Conversely, men with psychosocial burden have often leads to PE, leading to the question of which came first and making it difficult to scientifically establish causality (20). There are multiple psychological/behavioral treatments for PE, which may be used as a single therapy for natural variable PE or premature-like ejaculatory dysfunction or in combination with pharmacologic therapy for other subtypes of PE (10,37). Psychotherapy and sexual education can reduce patient anxiety, increase communication between a man and his partner, give patients more confidence, and modify many maladaptive sexual scripts (10,14,38). Behavioral therapy is primarily comprised of the “stop and start” technique, established by Semans (39) and a variation/modification of this technique, the ‘squeeze’ technique, proposed by Masters and Johnson (40). The aim of these methodologies is to help a patient maintain his sexual excitement just below the threshold for triggering ejaculation, by either stopping sexual activity or squeezing the head of the penis until the urge to ejaculate subsides (41). Desensitization of the penis via masturbation before sexual intercourse is a practice used by younger men and has proved effective in prolonging the ejaculatory period (42). These psychological/behavioral practices can lead to short-term improvement with overall success rates of 50-60% (43,44). However, as these methods require patient/partner commitment and practice to maintain viability, their efficacy decreases over time (45).

• Differential diagnosis: rule out erectile dysfunction, hormonal issues.
• Physical exam is part of assessment but often normal in PE.
• Validated questionnaires (e.g., PEDT) aid in diagnosis and monitoring.
• Treatment goal: satisfactory sexual experience for both partners.
• Dapoxetine addresses the biological, not solely psychological, aspect.
• May reduce performance anxiety secondary to PE.
• Prescribing guidelines emphasize starting at lowest effective dose.
• Long-term data on intermittent use over years is limited.

Topical local anesthetics such as lidocaine and/or prilocaine are the oldest drugs used for PE treatment. These are available in cream, gel and aerosol formulations (46,47). These agents delay ejaculation in theory by reducing the sensitivity of the glans penis. The use of topical anesthetics is a relatively efficacious, user friendly, and inexpensive modality for PE treatment (48). However, they can cause penile glans numbness and condom use or prior washing off before sexual activity is required to prevent transference of the drug to the vaginal mucosa (14).

Country	Approval Status	Notes
USA	Approved by FDA for PE	Prescription required
European Union	Approved in several countries	Prescription essential
Australia	Approved for PE	Sold under brand names
India	Available OTC in some pharmacies	Consult healthcare provider before use
Canada	Approved with prescription	Used for PE treatment

Another potential medical treatment option for PE is the phosphodiesterase type 5 (PDE-5) inhibitors.