Dapoxetine has received approval for the treatment of PE in over 50 countries worldwide.
| Side Effect | Frequency | Severity | Management Tips |
|---|---|---|---|
| Dizziness | Common | Mild | Sit or lie down, avoid driving |
| Headache | Common | Mild to moderate | Hydrate, take analgesics if needed |
| Nausea | Sometimes | Mild | Take with food |
| Insomnia | Rare | Mild | Practice good sleep hygiene |
| Fatigue | Rare | Mild | Rest and monitor symptoms |
Dapoxetine has not received marketing approval by the US Food and Drug Asministration. Dapoxetine is a potent SSRI (pKi = 8 nM), structurally similar to fluoxetine, with a pharmacokinetic profile suggesting a role as an on-demand treatment for PE [21]. Dapoxetine has a Tmax of 1.4–2.0 hours and a terminal half-life of 19 hours with a rapid decline of plasma levels to about 5% of Cmax at 24 hours, ensuring rapid absorption and achievement of peak plasma concentration with minimal accumulation [22-24]. Both plasma concentration and area under the curve (AUC) are dose dependent up to 100 mg and are unaffected by repeated daily dosing, food or alcohol. Food and ethanol do not have a clinically significant effect on dapoxetine pharmacokinetics [23].
"Dapoxetine for the treatment of premature ejaculation: results from a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries". "Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study". "Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction". "Dapoxetine-A Novel Drug for Premature Ejaculation".
"Dapoxetine for the treatment of premature ejaculation: Lack of interaction with ethanol". "Monoaminergic transporter binding and inhibition profile of dapoxetine, a medication for the treatment of premature ejaculation". "Physiology of ejaculation: emphasis on serotonergic control". "Supraspinal priligy 30 mg online site of action for the inhibition of ejaculatory reflex by dapoxetine". "Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials". No drug–drug interactions associated with dapoxetine, including phosphodiesterase inhibitor drugs, have been reported [25].
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Dapoxetine is extensively metabolized in the liver by multiple isozymes to multiple metabolites, including desmethyldapoxetine, didesmethyldapoxetine, and dapoxetine-n-oxide, which are eliminated primarily in the urine [22,24].
The initial reactant is trans-cinnamyl alcohol, which is commercially available. Sharpless asymmetric epoxidation and Mitsunobu reaction have been used to produce expected (S)-dapoxetine. This method is considered a good choice compared to the known methods due to high yield and easily obtainable reactants. Dapoxetine was created by Eli Lilly and in phase I clinical trial as an antidepressant. It never worked out well as a medication for the treatment of depression, though, and was shelved for a while before subsequently developed to treat PE.
In December 2003, Eli Lilly sold the patent for dapoxetine to Pharmaceutical Product Development (PPD) for US$65 million. Eli Lilly may also receive royalties payment from PPD if the sale exceeds a certain amount. Research into the effectiveness of dapoxetine was revisited in 2020. ALZA is the current owner of dapoxetine, but PPD will receive milestone payments and drug royalties from ALZA. If approved, dapoxetine will be marketed in the US by Ortho McNeil pharmaceutical, Inc. Although didesmethyldapoxetine is equipotent to the parent dapoxetine, its substantially lower plasma concentration, compared with dapoxetine, limits its pharmacological activity and it exerts little clinical effect, except when dapoxetine is coadministered with CYP3A4 or CYP2D6 inhibitors. Caution should be exercised in coadministration of dapoxetine and moderate CYP3A4 inhibitors and potent CYP2D6 inhibitors such as fluoxetine. The results of two phase 2 and six phase 3 trials have been published [26-33]. All were conducted prior to the development of the ISSM definition of L-PE and instead used Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and a baseline IELT ≤ 2 min on 75% of ≥4 sexual intercourse events as inclusion criteria [34,35].
An analysis of pooled phase 3 data from five randomized, placebo-controlled, phase 3 clinical trials comprised 6,081 men with a mean age of 40.6 years (range, 18–82 years) from 32 countries confirms that dapoxetine 30 and 60 mg taken 1–2 hours before intercourse is more effective than placebo from the first dose, resulting in a 2.5- and 3.0-fold increases in IELT, increased ejaculatory control, decreased distress, and increased satisfaction [36].
"Emerging treatments for premature ejaculation: focus on dapoxetine". "Dapoxetine: a novel treatment for premature ejaculation". "Stereoselective synthesis of (S)-dapoxetine starting from trans-cinnamyl alcohol". "Medical Non-Endocrine-Targeted Therapies: Ejaculatory Dysfunction and Immunotherapy". Dapoxetine (Priligy, Menarini, Florence, Italy) is the first compound specifically developed for the treatment of PE. Efficacy results were similar among each of the individual trials indicating that dapoxetine is consistently more efficacious than placebo regardless of a subject's demographic characteristics. Dapoxetine was comparably effective both in men with L-PE and A-PE [37] and was similarly effective and well tolerated in men with PE and comorbid ED treated with PDE5i drugs [32].
| Parameter | Value | Description |
|---|---|---|
| Absorption Rate | Fast | Peak plasma levels in 1-2 hours |
| Bioavailability | Approx. 85% | Percentage of dose reaching circulation |
| Half-Life | About 19 hours | Duration of main elimination phase |
| Metabolism | Liver (primarily CYP3A4) | Processes via hepatic enzymes |
| Excretion | Mainly in urine | Less in feces |
Across the phase 3 trials of dapoxetine, dapoxetine 30 and 60 mg were well priligy 30 mg 6 tablet tolerated with similar adverse event (AE) profiles [20]. In the integrated analysis of these studies [36], AEs occurred in 651/1,857 (35.1%), 760/1,616 (47.0%), 1,270/2,106 (60.3%), and 341/502 (67.9%) subjects with placebo, dapoxetine 30-mg prn, dapoxetine 60-mg prn, and dapoxetine 60-mg qd, respectively. Treatment-related side effects were uncommon, dose-dependent and included nausea, diarrhea, headache, dizziness, insomnia, somnolence, fatigue, and nasopharyngitis [36]. Severe or serious AEs occurred infrequently (∼3% and ≤1%, respectively), and most AEs were of mild to moderate severity [36].
Across trials, AE-related discontinuation occurred in 1.7–4.0% and 5.1–10.0% of subjects receiving dapoxetine 30 and 60 mg, respectively, most commonly because of nausea, dizziness, and diarrhea. Syncope (including loss of consciousness), which appeared to be vasovagal in nature and generally occurred within 3 hours of the first dose, was reported in 0.05%, 0.06%, and 0.23% of subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively [36]. Syncope occurred more frequently when dapoxetine was administered at one of the study sites (onsite [0.31%] vs. offsite [0.08%]), appeared to be related to syncope-associated onsite study procedures (e.g., blood draws or orthostatic maneuvers) and occurred almost exclusively with dapoxetine 60 mg, with only one reported episode with the 30-mg dose.
^ a b c priligy 30mg buy online "Australian Public Assessment Report for Dapoxetine" (PDF). "Pharmacokinetic and pharmacodynamic features of dapoxetine, a novel drug for 'on-demand' treatment of premature ejaculation". "Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation". ^ "Furiex Pharma gets rights to Priligy, some of which it sells on to Menarini". "New agents in the treatment of premature ejaculation".
"Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials". "Dapoxetine has long-term efficacy in the treatment of premature ejaculation". "AUA guideline on the pharmacologic management of premature ejaculation". "Dapoxetine: An Innovative Approach in the Therapeutic Management In Animal Model of Depression". "Antistress and antidepressant properties of dapoxetine and vortioxetine". Similar observations have been reported with other SSRIs, and these events resolved without sequelae.
^ "Dapoxetine: a guide to its use in premature ejaculation". "Pharmacokinetics of single and multiple escalating doses of dapoxetine in healthy volunteers". "Cardiovascular safety profile of dapoxetine during the premarketing evaluation". "Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports". "Selective serotonin reuptake inhibitor discontinuation syndrome: a review". Dapoxetine is the only agent for which studies have been adequately powered and designed to assess SSRI class-related effects in a PE population. Dapoxetine was not associated with treatment-emergent anxiety (measured by the Hamilton Anxiety Scale), depression (measured by the Montgomery–Åsberg Depression Rating Scale and the Beck Depression Inventory II), or suicidality [38]. Abrupt discontinuation of dapoxetine was not associated with an increased incidence of withdrawal syndrome compared with placebo or continued therapy (measured by the Discontinuation-emergent Signs and Symptoms Checklist) [38].
| Contraindication | Explanation | Recommendations |
|---|---|---|
| Allergic Reaction to Dapoxetine | History of hypersensitivity | Do not use |
| Use with MAO Inhibitors | Risk of severe interactions | Avoid at least 14 days prior |
| Liver Impairment | Increased drug levels | Dose adjustment or avoid |
| Heart Conditions | Potential impact on cardiovascular health | Consult cardiologist |
Unlike other SSRIs used to treat depression, which have been associated with high incidences of sexual dysfunction in depressed patients, dapoxetine was associated with low rates of sexual dysfunction in men with PE [38].
Ortho McNeil and Janssen-Ortho Inc, or Janssen-Cilag are all units of Johnson & Johnson. As at 2005, dapoxetine was in phase III clinical trials, pending review by the FDA. Dapoxetine has been marketed and approved in more than 50 countries. [39] Dapoxetine has been approved in Italy, Spain, Mexico, South Korea, and New Zealand in 2009 and 2010; marketed in Sweden, Austria, Germany, Finland, Spain, Portugal, and Italy. It has also been approved in France, Russia, Malaysia, Philippines, Argentina, and Uruguay.
784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Archived from the original on 2023-08-03. "Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors". "Dapoxetine: a new option in the medical management of premature ejaculation". ^ "Priligy is used to Treat Premature Ejaculation". The ISSM guidelines for the treatment of PE expert committee identified level 1a evidence to support the efficacy and safety of on-demand dosing of dapoxetine for the treatment of L-PE and A-PE [1].