Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: randomized, placebo-controlled, phase III study

The manufacturer therefore estimates that based on a GP-registered population of 100,000, 202 men aged 18 to 64 may potentially be prescribed dapoxetine over a 5-year period (A. Menarini Farmaceutica Internazionale: personal communication January 2014). The manufacturer estimated that in 2013 approximately 75% of European sales of dapoxetine were for the 30 mg strength. Dapoxetine for premature ejaculation was not considered appropriate for a NICE technology appraisal and is not currently planned into any other work programme.

There is no NICE guidance on premature ejaculation. A.

• Dapoxetine helps improve sexual performance and decrease performance anxiety.
• It is a part of a broader treatment approach for premature ejaculation.
• Not recommended for men with a history of seizures or heart issues.
• Dapoxetine's effects may vary depending on individual health factors.
• Combining dapoxetine with other medications should only be done under supervision.
• Always follow dosage instructions to ensure safety and efficacy.

Menarini Farmaceutica Internazionale (2013) Priligy 30 mg and 60 mg film-coated tablets summary of product characteristics [online; accessed 12 March 2014] Buvat J, Tesfaye F, Rothman M et al. (2009) Dapoxetine for the treatment of premature ejaculation: results from a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries.

Publication types

Because longer-acting SSRIs such as citalopram, fluoxetine or paroxetine have a longer onset of action than the shorter-acting dapoxetine they need to be taken on a daily basis and cannot be used as an 'on demand' treatment. The European Association of Urology 2014 guidelines on male sexual dysfunction states that in men for whom premature ejaculation causes few if any problems treatment should be limited to psychosexual counselling and education. The guidelines recommend that before beginning treatment, it is essential to discuss the expectations of treatment thoroughly. Various behavioural techniques have demonstrated benefit in treating premature ejaculation and are indicated for men who are uncomfortable with pharmacological therapy. In lifelong premature ejaculation, the European guidelines state that behavioural techniques are not recommended for first-line treatment because they are time-intensive, require the support of a partner and can be difficult to do.

Priligy side effects

The guidelines recommend that pharmacological treatment options include 'on demand' dapoxetine and daily use of a longer-acting SSRI such as citalopram, fluoxetine or paroxetine (off-label use) or daily use of clomipramine (off-label use). Dapoxetine is taken 'on demand' approximately 1 to 3 hours before anticipated sexual activity. This may reduce the incidence of SSRI-related adverse effects compared with the off-label use of once-daily longer acting SSRIs, although there are no direct RCTs to provide evidence for this. However, some men may prefer to take a daily dose which may allow more spontaneity than a planned 'on demand' treatment. Dapoxetine is licensed for treating premature ejaculation in adult men aged 18 to 64 years. European Association of Urology (2014) Guidelines on male sexual dysfunction [online; accessed 11 April 2014] Kaufman JM, Rosen RC, Mudumbi RV et al.

(2009) Treatment benefit of dapoxetine for premature ejaculation: results from a placebo-controlled phase III trial.

(2010) Treatment of premature ejaculation in the Asia-Pacific region: results from a phase III double-blind, parallel-group study of dapoxetine. The Journal of Sexual Medicine 7: 256–68 McMahon CG, Althof SE, Kaufman JM et al. (2011) Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials.

What do we need to know?

The summary of product characteristics states that dapoxetine should only be prescribed to men who meet all the following criteria: An intravaginal ejaculatory latency time of less than 2 minutes and An intravaginal ejaculatory latency time of less than 2 minutes and Persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the man wishes and Persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the man wishes and Marked personal distress or interpersonal difficulty as a consequence of premature ejaculation and Marked personal distress or interpersonal difficulty as a consequence of premature ejaculation and A history of premature ejaculation in the majority of intercourse attempts over the prior 6 months. Therefore, men will need to be appropriately assessed and given a diagnosis of premature ejaculation in line with the above criteria before dapoxetine can be considered. In addition, the summary of product characteristics states that a careful appraisal of the individual benefit/risk ratio should be carried out after the first 4 weeks of treatment (or at least after 6 doses of treatment) to determine whether continuing treatment is appropriate. If dapoxetine is continued, the benefit/risk balance should be re-evaluated at least every 6 months. Consideration will need to be given to how treatment efficacy can be assessed given the subjective nature of efficacy outcomes.

Report side effects to a medicine or vaccine

Premature ejaculation can occur in conjunction with erectile dysfunction and the European Association of Urology 2014 guidelines on male sexual dysfunction states that if premature ejaculation is secondary to erectile dysfunction then the erectile dysfunction should be treated before or at the same time as the premature ejaculation. It should be noted however, that the summary of product characteristics states that dapoxetine should not be used in men taking phosphodiesterase type 5 inhibitors (for example, sildenafil) as this increases the risk of syncope. For a number of men pharmacological treatment of premature ejaculation will not be acceptable. A prospective observational study from a single clinical centre in Italy (Mondaini et al. 2013) assessed the acceptance and discontinuation rates of 'on demand' dapoxetine 30 mg (titrated to 60 mg after 3 months dapoxetine order online if low efficacy) in 120 men with lifelong premature ejaculation. (2014) Results from a prospective observational study of men with premature ejaculation treated with dapoxetine or alternative care: The PAUSE study.

Premature Ejaculation: Common, Treatable, and Often Under-Discussed

Twenty-four (20%) of the men decided not to start dapoxetine. Fear of using a 'drug' was the most frequently reported reason for treatment non-acceptance (50%). In addition, the majority of men who took dapoxetine discontinued treatment. The main reasons for treatment discontinuation were efficacy below expectations, side effects and costs. Out of the 96 men who decided to start dapoxetine, only 10 men were continuing the treatment after 1 year.

Intravaginal ejaculatory latency time (IELT)

Dapoxetine is the only medicine licensed in the UK for the treatment of premature ejaculation, although other treatments are used off-label for this indication. The General Medical Council advice to use a licensed medicine whenever possible should be taken into consideration. The manufacturer has estimated that based on a GP-registered population of 100,000 people, 5851 men aged 18 to 64 will be affected by premature ejaculation with 1151 men severely affected (A. Menarini Farmaceutica Internazionale: personal communication January 2014). The manufacturer further estimates that 25% of the men severely affected by premature ejaculation will seek treatment and 70% of those seeking treatment could be prescribed dapoxetine. (2013) Dapoxetine treatment in patients with lifelong premature ejaculation: the reasons of a 'Waterloo'. (2006) Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomized controlled trials Lancet 368: 929–37 The integrated process statement sets out the process NICE uses to select topics for the evidence summaries: new medicines and how the summaries are developed, quality assured and approved for publication.

• Dapoxetine is sometimes used off-label to treat other sexual dysfunctions.
• It is not a cure but a symptom management medication.
• Men should discuss potential side effects thoroughly before starting treatment.
• The medication has been studied and approved in several countries for PE.
• In case of overdose, seek emergency medical help immediately.
• Dapoxetine use requires careful monitoring for long-term safety.

Ian Pearce, Consultant Urological Surgeon, Honorary Senior Lecturer, University of Manchester, Manchester Royal Infirmary Mike Foster, Consultant Urologist, Heart of England NHS Trust Dapoxetine is a medicine used for the treatment of premature ejaculation (a sexual dysfunction in which a man ejaculates too quickly during sexual intercourse). This medicine helps in increasing the time taken to ejaculate and achieving better control over ejaculation during sexual intercourse.

Does dapoxetine affect testosterone levels?

The efficacy outcomes were reported to be based on the intention-to-treat (ITT) population, classed as all randomised participants. However, in the pooled analysis, numbers of participants for whom data were available was also presented. It is unclear if the analysis was based on the ITT population or the population for whom data were available. Discontinuation rates were high in the studies but were similar for dapoxetine and placebo (31.1% of all participants in the dapoxetine groups and 28.9% of all participants in the placebo groups). For missing data post-baseline, the last post-baseline observation carried forward (LPOCF) method was used.

Introduction and current guidance

In this approach, regardless of when a patient left the trial (for example, after week 1, week 6 or week 12), the last available result for that patient was carried forward and analysed as though it were the result at the study end. As stated in the summary of product characteristics, the efficacy and safety of dapoxetine in men with both premature ejaculation and erectile dysfunction treated with both dapoxetine and phosphodiesterase type 5 inhibitors (for example, sildenafil) has not been established. The summary of product characteristics states that dapoxetine should not be used in men taking phosphodiesterase type 5 inhibitors. There are limited data available on the safety and efficacy of dapoxetine 'on demand' for longer than 24 weeks. The European Association of Urology 2014 guidelines on male sexual dysfunction recommend that pharmacological treatment options include 'on demand' dapoxetine, daily use of a longer-acting selective serotonin reuptake inhibitor (SSRI) [off-label use], daily use of clomipramine (off-label use), 'on demand' topical local anaesthetic agents (off-label use) and 'on demand' tramadol (off-label use). Dapoxetine has some side effects like dizziness, headache, nausea, and sweating. These side effects may subside by themselves.

• Dapoxetine has been shown to significantly increase ejaculatory latency time.
• It is not intended to treat all aspects of sexual dysfunction.
• Use of dapoxetine may require dose adjustments based on side effects.
• The medication should be stored safely out of children's reach.
• Monitoring response and side effects enhances safe use of dapoxetine.
• Dapoxetine should be used only as part of a broader treatment plan.

Consult your doctor if they bother you for a long time or become severe.