Key points from the evidence | Premature ejaculation: dapoxetine | Advice

Summary

Dapoxetine is a short-acting selective serotonin-reuptake inhibitor (SSRI). It is the first pharmacological treatment for premature ejaculation to be licensed in the UK. In a pooled analysis of 4 randomised controlled trials (RCTs) in men with premature ejaculation there was a statistically significant increase in intravaginal ejaculatory latency time (IELT) with dapoxetine 'on demand' compared with placebo 'on demand', although an increase in IELT was also seen with placebo.

Effectiveness

Statistically significant increase in IELT from baseline with dapoxetine 30 mg and 60 mg 'on demand' compared with placebo 'on demand' (from 0.9 minutes in all groups to 1.9, 3.1 and 3.6 minutes respectively for placebo, dapoxetine 30 mg and dapoxetine 60 mg; p<0.001 for comparisons with placebo, pooled analysis of 4 RCTs, n=4843).
Statistically significantly more men reported that their premature ejaculation was 'better' or 'much better' with dapoxetine compared with placebo (30.7% and 38.3% with dapoxetine 30 mg and 60 mg respectively compared with 13.7% with placebo; p<0.001 for comparisons with placebo, pooled analysis of 4 RCTs, n=4843).

Safety

Orthostatic hypotension and syncope was reported in clinical trials and the summary of product characteristics includes recommendations to minimise the risk of this.
Treatment with dapoxetine should not be initiated with the 60 mg dose. The incidence and severity of adverse events is higher with the 60 mg dose.

User factors

Men will need to be appropriately assessed and given an accurate diagnosis of premature ejaculation in line with the indication in the summary of product characteristics before dapoxetine can be considered.
Dapoxetine is taken 'on demand' approximately 1 to 3 hours before anticipated sexual activity.
The summary of product characteristics states that dapoxetine should not be used in men taking phosphodiesterase type 5 inhibitors (for example, sildenafil).
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) with dapoxetine to determine whether continuing treatment is appropriate. If dapoxetine is continued the benefit/risk balance should be re-evaluated at least every 6 months.
Men will need to balance the potential benefits with the likelihood of very common (greater than 1 in 10 men) adverse reactions of dizziness, headache and nausea reported in the summary of product characteristics.

Resource implications

The cost of dapoxetine ranges from £14.71 for a pack of 3×30 mg tablets to £34.42 for a pack of 6×60 mg tablets.
The estimated cost of 30 days' supply of a longer-acting SSRI taken daily (off-label use) ranges from £0.94 to £6.38 depending on the SSRI used and the dosage.

Introduction and current guidance

In the Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM-IV-TR), premature ejaculation is defined as a 'persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it. The clinician must take into account factors that affect duration of the excitement phase, such as age, novelty of the sexual partner or situation, and recent frequency of sexual activity.' The European Association of Urology 2014 guidelines on male sexual dysfunction state that although premature ejaculation is a very common male sexual dysfunction (with prevalence rates of 20% to 30%), the aetiology of premature ejaculation is unknown, with little data to support suggested biological and psychological hypotheses. Despite the possible serious psychological and quality of life consequences of premature ejaculation, few men seek treatment.

Full text of Introduction and current guidance.

Product overview

Dapoxetine (Priligy) is licensed in the UK for the 'on demand' treatment of premature ejaculation in adult men aged 18 to 64 years. 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 (IELT) 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
Marked personal distress or interpersonal difficulty as a consequence of premature ejaculation and
Poor control over ejaculation and
A history of premature ejaculation in the majority of intercourse attempts over the prior 6 months.

The summary of product characteristics states that dapoxetine should not be prescribed to delay ejaculation in men who have not been diagnosed with premature ejaculation. The starting dose recommended in the summary of product characteristics for all men is 30 mg, taken as needed approximately 1 to 3 hours prior to sexual activity.

Full text of Product overview.

Evidence review

This evidence summary is based on a pooled analysis of results from 5 phase III RCTs (McMahon et al. 2011) in men with premature ejaculation; 4 of the RCTs contributed to the main efficacy outcome. These 4 RCTs (n=4843) compared dapoxetine 30 mg and 60 mg 'on demand' with placebo 'on demand' for IELT (defined as the duration of time from penetration to intravaginal ejaculation and measured by a stopwatch held by the female partner during each intercourse episode).
The pooled analysis showed that there was an increase from baseline in mean IELT at 12 weeks with all 3 groups including the placebo group. There was a statistically significantly greater increase from baseline in mean IELT at 12 weeks with both dapoxetine 30 mg and 60 mg 'on demand' compared with placebo 'on demand' (from 0.9 minutes in all groups to 1.9, 3.1 and 3.6 minutes respectively for placebo, dapoxetine 30 mg and dapoxetine 60 mg; p<0.001 for comparisons with placebo).
Pryor et al. (2006) concluded that the minimum clinically important change in IELT seems to be about 1 minute based on a correlation of global impression of change scores with mean changes in IELT. However, in clinical practice a minimum clinically important change in IELT has not been defined. In the pooled analysis, the improvement in mean 12-week IELT from baseline for the placebo group was 1 minute and the difference between placebo and dapoxetine 30 mg for the improvement in mean 12-week IELT was 1.2 minutes. In both the pooled analysis and the individual studies, the difference between dapoxetine 30 mg and 60 mg 'on demand' for the mean IELT at 12 weeks was less than 1 minute.
Very common (greater than 1 in 10 men) adverse reactions reported in the summary of product characteristics are dizziness, headache and nausea. Contraindications to the use of dapoxetine include significant pathological cardiac conditions such as heart failure, significant ischaemic heart disease or history of syncope; a history of mania or severe depression; moderate and severe hepatic impairment; and concomitant treatment with monoamine oxidase inhibitors, thioridazine, SSRIs, tricyclic antidepressants or other herbal/medicinal products with serotonergic effects and potent CYP3A4 inhibitors. The summary of product characteristics states that men should be advised not to use dapoxetine in combination with recreational drugs or alcohol. Treatment with dapoxetine should not be initiated with the 60 mg dose. If a man has an orthostatic reaction on the 30 mg dose, the dose should not be increased to 60 mg. For further information on contraindications, cautions and warnings please refer to the summary of product characteristics.
There are no RCTs that compare 'on demand' dapoxetine with an active comparator such as daily use of a longer-acting SSRI (off-label use). In addition, there are limited data available on the safety and efficacy of dapoxetine 'on demand' for longer than 24 weeks. The studies only included men aged 18 years and over (the average age in the pooled analysis was 41 years) in a monogamous heterosexual relationship for at least 6 months who met DSM-IV-TR criteria for premature ejaculation. The efficacy and safety of dapoxetine have not been established in men aged 65 years and over.

Full text of Evidence review.

Context

The European Association of Urology 2014 guidelines on male sexual dysfunction recommend that non-pharmacological treatments for premature ejaculation which are beneficial include psychosexual counselling, education, and behavioural treatments. Pharmacological treatment options for premature ejaculation include 'on demand' dapoxetine, daily use of a longer-acting SSRI (off-label use), daily use of clomipramine (off-label use), 'on demand' topical local anaesthetic agents (off-label use) or 'on demand' tramadol (off-label use).

Full text of Context.

Estimated impact for the NHS

The European Association of Urology 2014 guidelines on male sexual dysfunction state that in men for whom premature ejaculation causes few if any problems treatment should be limited to psychosexual counselling and education. For a number of men, pharmacological treatment of premature ejaculation will not be acceptable. Various behavioural techniques have demonstrated benefit in treating premature ejaculation and are indicated for men uncomfortable with pharmacological therapy. In lifelong premature ejaculation (onset from the first sexual experience and remaining during life), 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. Pharmacotherapy is recommended as first-line therapy.

The summary of product characteristics for dapoxetine 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) with dapoxetine to determine whether continuing treatment is appropriate. If dapoxetine is continued the benefit/risk balance should be re-evaluated at least every 6 months.

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.

Full text of Estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.