Short facts about premature ejaculation and Priligy
Premature ejaculation is thought to be the most common male sexual dysfunction, often causing interpersonal distress, affecting self-confidence and sexual relationships. However, it is a condition that appears to be highly undertreated, and there are many differences among sex health experts in their understanding of premature ejaculation. Educational activities are considered crucial in implementing new guidelines on premature ejaculation. The underlying pathophysiology of premature ejaculation is not completely understood, although both physiological and psychological components could contribute to the condition. Psychopharmacological studies suggest that premature ejaculation might be related to diminished serotonergic neurotransmission through pathways that control ejaculation.2
In 2016, the International Society for Sexual Medicine recently developed a unified definition for lifelong and acquired premature ejaculation: “Premature ejaculation is a male sexual dysfunction characterized by:
- Ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong premature ejaculation), OR a clinically significant reduction in latency time, often to about 3 minutes or less (acquired premature ejaculation)
- The inability to delay ejaculation on all or nearly all vaginal penetrations
- Negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy.”
Priligy is a drug used with success in treating Premature Ejaculation and containing Dapoxetine, a drug belonging to the selective serotonin reuptake inhibitors (SSRIs), which were developed to treat depression and other psychiatric disorders. It has been granted marketing authorization in 33 countries worldwide, including 7 countries in the European Union. The approved use in the EU is for the treatment of premature ejaculation in men 18 to 64 years of age.
Dapoxetine has a unique pharmacokinetic profile, with a short time to maximum serum concentration (about 1hr) and rapid elimination (initial half-life of 1,2hr). Priligy’s efficacy and tolerability were tested in several clinical trials and the results confirmed that Dapoxetine is effective, generating satisfaction in patients reported outcomes and improvement of intravaginal ejaculatory latency times (IELT).
The Dapoxetine Study Group
As part of a development program, the Dapoxetine Study Group was involved in the design and performance of two large multicenter, randomized, double-blind, placebo-controlled, 12-week clinical trials of identical design (June 2003 – June 2004.) The studies comprised 2614 males with premature ejaculation that consented to their participation in 121 clinical facilities in the United States of America. The objectives of the study group were to analyze the effectiveness of Priligy (Dapoxetine) and the safety profile of Priligy.
Couples were instructed to attempt sexual intercourse four or more times during the 2-week baseline period and six or more times per month during the 12-week treatment period (minimum of 24 h between doses of medication). They were to record IELT for the first event after each dose in the event log. At the end of the baseline period, patients were stratified based on average IELT during the previous 2 weeks of 1 minute or less or more than 1 minute.
At each center, patients were randomly assigned within each stratum 1:1:1, by a computerized interactive voice recognition system to receive a placebo, 30mg Dapoxetine, or 60mg Dapoxetine, and given 30 doses of study medication (one dose was two tablets; tablets in all groups were identical in appearance); one dose was to be taken 1–3 h before anticipated sexual intercourse, and only one dose was allowed per 24-h period. Dapoxetine doses of 30mg and 60mg were selected based on efficacy and safety findings from two previously completed phase II studies in which Dapoxetine doses ranged from 20 mg to 100 mg, taken as needed.5 Laboratory testing was performed at a screening on week 4, and week 12.
Common adverse events reported by The Dapoxetine Study Group
Common adverse events (appeared in 30mg and 60mg Dapoxetine-treated patients) were nausea (8.7% and 20.1%), diarrhoea (3.9% and 6.8%), headache (5.9% and 6.8%), and dizziness (3% and 6.2%) and seemed to be dose-related.
Accidental injuries—eg, sprained ankle, car accident— were reported in 17 (1.9%) patients receiving placebo, in 28 (3.2%) patients receiving 30mg Dapoxetine and in 26 (3%) on 60 mg Dapoxetine. Dizziness and somnolence were the most common neurocognitive adverse events reported.
Cardiovascular adverse events occurred in less than 2% of patients and the most clinically significant event reported was syncope. Syncope was reported in both patients taking placebo and patients taking Dapoxetine as follows: two individuals (0.2%) receiving placebo, three (0.3%) receiving 30 mg Dapoxetine and two (0.2%) receiving 60 mg Dapoxetine.
Mean blood pressure and heart rate throughout the study were much the same for active treatment and placebo.
The Dapoxetine Study Group concluded that Dapoxetine, given 1–3 h before intercourse, increased IELT significantly, even after administration of the first dose. Dapoxetine also improved patients’ perception of control over ejaculation, satisfaction with sexual intercourse, and overall impression of change in condition. Partners benefited through improved satisfaction with sexual intercourse. Thus, Dapoxetine seemed to lead to improvements in ejaculatory function that have meaning for men with premature ejaculation and their partners.4
Dapoxetine studies explore further…
A blockbuster clinical trial with the objective to evaluate the long-term (6-month) efficacy and safety of Dapoxetine in men with PE was conceived taking into study population from 22 countries affected by premature ejaculation. The selected countries were Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, the Czech Republic, Finland, France, Germany, Hungary, Israel, Italy, Mexico, the Netherlands, Norway, Poland, Portugal, South Africa, Spain, Sweden, and the United Kingdom.6 More safety assessments were performed, including Holter monitoring (first dose; 10 min before to 3 h after), changes in clinical laboratory results (each 4-wk visit), and vital signs (from baseline to study endpoint). Known drug class effects were monitored at baseline and at week 4, week 12, and week 24 using clinical and study-specific scales. Adverse events were reported by 38.4%, 56.2%, and 68.1% of men receiving placebo, Dapoxetine 30 mg, and Dapoxetine 60 mg, respectively.
Similar to previous studies, the most common treatment-emergent adverse effects were nausea, dizziness, diarrhoea, and headache. Nausea with Dapoxetine 30mg and Dapoxetine 60mg was usually mild and intermittent. The most common adverse event leading to discontinuation was nausea. With Dapoxetine 30mg, ventricular tachycardia and transient ischemic attack were considered possibly related to treatment. With Dapoxetine 60mg, one subject experienced sinus bradycardia and sinus arrest (both severe; very likely related to treatment) associated with syncope accompanied by loss of consciousness approximately 1 h after dosing on day 1 (prodromal symptom: nausea). Following this event, a protocol amendment required a modified consent form and new patient instructions for minimizing the risk of syncope.
Another subject receiving Dapoxetine 60mg experienced syncope accompanied by a loss of consciousness on day 63. There were no reports of syncope with loss of consciousness occurred with Dapoxetine 30mg. No clinically relevant effects on clinical laboratory tests were noted, nor was there any clear effect of Dapoxetine on mean supine and standing blood pressure. Dr Emmanuelle A. Jannini7, in an editorial comment after the publication of the study results, expressed her opinion about the safety profile of Dapoxetine.
“Due to its particularly short half-life, Dapoxetine should have a better safety profile, leading to a risk-benefit ratio definitively in favour of the benefits. In fact, Dapoxetine was well tolerated in this study: Adverse events appeared early in treatment, were usually dose dependent, and generally did not lead to discontinuation. This is very important information for the clinician treating premature ejaculation.”
Safety issues reported from European Medicines Agency
Against a background of a post-marketing exposure estimated to 850,000 patients only 9 events of syncope have been spontaneously reported, 5 of which are medically confirmed and 4 of which are unconfirmed. These events were of short duration and spontaneously resolved.
Interim data (4,002 patients treated with Priligy) from the observational post-marketing safety study (R096769-PRE-4001) show:
− No events of syncope have been reported;
− 92% of patients were prescribed treatment according to the SmPC, i.e. initiation of treatment with 30 mg;
− More than 98% of the patients prescribed Priligy found that the Patient Brochure and PIL were understandable, and felt that the information regarding Priligy dosing and Priligy safety was helpful.8
- Dapoxetine (Priligy) significantly improved all aspects of premature ejaculation and was generally well tolerated in a broad population.
- Dose-related effects including nausea, diarrhoea, dizziness, headache, insomnia, and fatigue, which are typical of drug class, can appear when using Priligy.
- Considering that premature ejaculation is not a life-threatening disease, the added benefit of 60 mg compared to 30 mg (5-10% more responders) was considered too modest to outweigh the potentially increased risk for severe events of syncope.
- If you are intending to use Priligy, or if you have questions related to side-effects, please talk directly to our pharmacy or to our doctor at phone number 01625 460621.
- Rowland DL, Perelman MA, Althof SE, et al. Self-reported premature ejaculation and aspects of sexual functioning and satisfaction. J Sex Med 2004; 1: 225–32.
- Waldinger MD, Berendsen HH, Blok BF, Olivier B, Holstege G. Premature ejaculation and serotonergic antidepressants-induced delayed ejaculation: the involvement of the serotonergic system. Behav Brain Res. 1998; 92: 111–18.
- Shechter A, Lowenstein L, Serefoglu EC, Reisman Y. Attitudes of Sexual Medicine Specialists Toward Premature Ejaculation Diagnosis and Therapy. Sex Med. 2016 Sep;4(3):e209-16. doi: 10.1016/j.esxm.2016.05.001. Epub 2016 Jun 23. PubMed PMID: 27346231; PubMed Central PMCID: PMC5005309.
- Pryor JL, Althof SE, Steidle C, Rosen RC, Hellstrom WJ, Shabsigh R, Miloslavsky M, Kell S; Dapoxetine Study Group. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials. Lancet. 2006 Sep 9;368(9539):929-37. PubMed PMID: 16962882.
- Hellstrom W, Althof S, Gittelman M, et al. Dapoxetine for the treatment of men with premature ejaculation (PE): dose-finding analysis. J Urol 2005; 173 (suppl 4): 238
- Buvat J, Tesfaye F, Rothman M, Rivas DA, Giuliano F. Dapoxetine for the treatment of premature ejaculation: results from a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries. Eur Urol. 2009 Apr;55(4):957-67. doi: 10.1016/j.eururo.2009.01.025. Epub 2009 Jan 21. PubMed PMID: 19195772.
- Jannini EA, Lenzi A. Ejaculatory disorders: epidemiology and current approaches to definition, classification and subtyping. World J Urol 2005;23:68–75.
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