Dapoxetine Safety Profile and Side Effects

[33][34] The lack of chronic serotonergic stimulation with on-demand dapoxetine minimizes the potentiation action of serotonin at synaptic cleft, thus decreasing the risk of discontinuation symptoms.

Special Dietary & Lifestyle Recommendation

No cardiovascular adverse had been found. Studies of SSRIs in patients with major psychiatric disorders prove that SSRIs are potentially associated with certain neurocognitive adverse effects such as anxiety, akathisia, hypomania, changes in mood, or suicidal thought. [30][31] No study on the effects of SSRIs in men with PE has been done. McMahon's study in 2012 showed that dapoxetine has no effect on mood and is not associated with anxiety or suicidality. The incidence of antidepressant discontinuation syndrome symptoms in men using dapoxetine to treat PE has been described by reviewers as low or no different from the incidence of such symptoms in men withdrawn from placebo treatment. Currently, very few methods are used to synthesize (S)-dapoxetine. This novel approach consists of only six steps in which three main steps are shown above.

Product	Dosage	Quantity + Bonus	Price
Kamagra Gold	100 mg	360 + 6 Pills	839.95€ 799.95€	Buy
Cialis Professional	20mg	120 + 4 Pills	291.68€ 277.79€	Buy
Priligy Generic Dapoxetine	60mg	30 + 6 Pills	106.65€ 101.57€	Buy
Viagra Generic	150mg	270 + 10 Pills	326.61€ 311.06€	Buy
Kamagra Oral Jelly	100mg	220 + 18 Sachets	662.24€ 630.70€	Buy
Priligy Generic Dapoxetine	60mg	20 + 4 Pills	77.31€ 73.63€	Buy
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Priligy Generic Dapoxetine	60mg	120 + 10 Pills	341.26€ 325.01€	Buy
Viagra Original	100mg	34 + 2 Pills	163.67€ 155.88€	Buy
Cialis Super Active	20mg	60 + 8 Pills	230.32€ 219.35€	Buy
Cialis Generic	20mg	20 Pills	54.72€ 52.11€	Buy
Cialis Soft Tabs	20mg	90 + 6 Pills	216.71€ 206.39€	Buy
Priligy Generic Dapoxetine	60mg	10 Pills	47.63€ 45.36€	Buy
Kamagra Effervescent Tablets	100 mg	42 + 7 Pills	122.97€ 117.11€	Buy
Priligy Generic Dapoxetine	60mg	60 + 8 Pills	183.06€ 174.34€	Buy
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Priligy Generic Dapoxetine	60mg	90 + 10 Pills	265.64€ 252.99€	Buy

The initial reactant is trans-cinnamyl alcohol, which is commercially available.

Year	Number of Prescriptions	Percentage Change	Notes
2018	50,000	-	Steady growth in early years
2019	60,000	+20%	Increased awareness
2020	70,000	+16.7%	Pandemic impact, more online use
2021	85,000	+21.4%	Marketing efforts, new regulations
2022	90,000	+5.9%	Market saturation begins

Sharpless asymmetric epoxidation and Mitsunobu reaction have been used to produce expected (S)-dapoxetine.

Uses of Dapoxetine

Originally created by Eli Lilly pharmaceutical company, dapoxetine was sold to Johnson & Johnson in 2003 and submitted as a New Drug Application to the US Food and Drug Administration (FDA) for the treatment of PE in 2004. [8] Dapoxetine is sold in several European and Asian countries, and in Mexico. In the US, dapoxetine has been in phase III development. In May 2012, US-based Furiex Pharmaceuticals reached an agreement with ALZA Corp and Janssen Pharmaceuticals to market dapoxetine in the United States, Japan, and Canada, while selling the rights to market the drug in Europe, most of Asia, Africa, Latin America, and the Middle East to Menarini. Randomized, double-blind, placebo-controlled trials have confirmed the efficacy of dapoxetine for the treatment of PE.

Generic Names

[10] Different dosages have different impacts on different types of PE. Dapoxetine 60 mg significantly improves the mean intravaginal ejaculation latency time (IELT) compared to that of dapoxetine 30 mg in men with lifelong PE, but no difference is seen in men with acquired PE. [11] Dapoxetine, given 1–3 hours before sexual episode, prolongs IELT and increases the sense of control and sexual satisfaction in men of 18 to 64 years of age with PE. Since PE is associated with personal distress and interrelationship difficulty, dapoxetine provides help for men with PE to overcome this condition. With no drug approved specifically for treatment for PE in the US and some other countries, other SSRIs such as fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram have been used off-label to treat PE. 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.

Source Type	Typical Price per 30mg Tablet (€)	Discount Offers	Quality Assurance	Notes
Local Pharmacy Chain	1.00 – 1.50	Often discounts for bulk	Certified products	Check expiry date
Online Authorized Pharmacies	0.80 – 1.30	Bulk purchase discounts	Verified suppliers	Delivery time may vary
Imported Versions	1.20 – 2.00	No discounts	Varies	Potential import taxes

In December 2003, Eli Lilly sold the patent for dapoxetine to Pharmaceutical Product Development (PPD) for US$65 million.

• Dapoxetine's chemical name is (S)-(+)-N,N-dimethyl-(α)-[2-(1-naphthalenyloxy)ethyl]-benzenemethanamine.
• Its molecular formula is C21H23NO, and it is formulated as dapoxetine hydrochloride.
• The tablet contains film-coated granules for modified release of the active ingredient.
• The mechanism involves inhibition of serotonin reuptake, increasing synaptic concentration.
• This action in the hypothalamic and limbic areas modulates the ejaculatory reflex.
• It has a rapid absorption and elimination profile suited for on-demand use.
• Peak plasma concentration is reached in approximately 1-2 hours post-dose.
• It is extensively metabolized in the liver by multiple enzyme systems (CYP450).
• Excretion is primarily via urine as metabolites, with a half-life of about 1.5 hours.

Eli Lilly may also receive royalties payment from PPD if the sale exceeds a certain amount.

Safety and tolerability

These plasma samples were then analyzed using liquid chromatography-tandem mass spectrometry. The results showed that dapoxetine does not alter the pharmacokinetics of tadalafil or sildenafil. Alcohol does not affect the pharmacokinetics of dapoxetine when taking concurrently. The mechanism through which dapoxetine affects premature ejaculation is still unclear, but dapoxetine is presumed to work by inhibiting serotonin transporter (SERT) and subsequently increasing serotonin's action at pre- and postsynaptic receptors. [22] Human ejaculation is regulated by various areas in the central nervous system (CNS).

Molecular Weight

These signals are passed on to the brain stem, which then is influenced by a number of nuclei in the brain such as medial preoptic and paraventricular nuclei. [24] Clement's study performed on anaesthetized male rats showed that acute administration of dapoxetine 5mg dapoxetine inhibits ejaculatory expulsion reflex at supraspinal level by modulating activity of lateral paragigantocellular nucleus (LPGi) neurons. These effects cause an increase in pudendal motoneuron reflex discharge (PMRD) latency, though whether dapoxetine acts directly on LPGi or on the descending pathway in which LPGi located is unclear. Dapoxetine is a white, powdery, water-insoluble substance. Taken one to three hours before sexual activity, it is rapidly absorbed in the body. Research into the effectiveness of dapoxetine was revisited in 2020.

Side Effects of Tadalafil and Dapoxetine

Waldinger's meta-analysis shows that the use of these conventional antidepressants increases IELT two- to nine-fold above baseline, compared to three- to eight-fold when dapoxetine is used. [11] However, these SSRIs may need to be taken daily to achieve meaningful efficacy, and their comparatively longer half-lives increase the risk of drug accumulation and a corresponding increase of adverse effects such as reduced libido. [13] Dapoxetine, though, is generally categorized as a fast-acting SSRI. It is more rapidly absorbed and mostly eliminated from the body within a few hours. These pharmacokinetics are more favorable in that they might minimize drug accumulation in the body, habituation, and side effects.

Foreign Names

Dapoxetine was initially considered unsuccessful in its intended use as an antidepressant; however, it has since been investigated as a possible aid to an approach to depression treatment focused on stress reduction, based on an animal model of depression. Dapoxetine should not be used in men with moderate to severe hepatic impairment and in those receiving CYP3A4 inhibitors such as ketoconazole, ritonavir, and telithromycin. Dapoxetine also cannot be used in patients with heart failure, permanent pacemaker, or other significant ischemic heart disease. Caution is advised in men receiving thioridazine, monoamine oxidase inhibitors, SSRIs, serotonin-norepinephrine reuptake inhibitors, or tricyclic antidepressants. If a patient stops taking one of these drugs, he should wait for 14 days before taking dapoxetine. ALZA is the current owner of dapoxetine, but PPD will receive milestone payments and drug royalties from ALZA.

Trend	Description	Expected Impact	Challenges
Increased Online Access	Growth in online pharmacy sales	Wider availability and convenience	Ensuring product authenticity
Expanded Demographic Use	Use among older populations for sexual health	Broader market potential	Medical supervision required
Regulatory Changes	Possible updates to prescription rules	Might increase accessibility	Balance between safety and access

If approved, dapoxetine will be marketed in the US by Ortho McNeil pharmaceutical, Inc. Ortho McNeil and Janssen-Ortho Inc, or Janssen-Cilag are all units of Johnson & Johnson.

Study Overview

Its maximum plasma concentration (Cmax) is reached one to two hours after oral administration. The Cmax and AUC (area under the plasma vs. time curve) is dose dependent. The Cmax and Tm (time needed to obtain the maximum plasma concentration) after single doses of dapoxetine 30 mg and 60 mg are 297 and 498 ng/ml at 1.01 and 1.27 hours, respectively. A high-fat meal does reduce the Cmax slightly, but it is insignificant.

Depression and anxiety

It can be taken with or without food. Dapoxetine is absorbed and distributed rapidly in the body. The mean steady-state volume is 162 L. Its initial half-life is 1.31 hours (30 mg dose) and 1.42 hours (60 mg dose), and its terminal half life is 18.7 hours (30 mg dose) and 21.9 hours (60 mg dose). Dapoxetine is metabolized extensively in the liver and kidney by multiple enzymes such as CYP2D6, CYP3A4, and flavin monooxygenase 1. 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.

• Patient privacy is protected under Spanish data protection laws (LOPDGDD).
• Medical discussions about PE are confidential between you and your doctor.
• You have the right to access your medical records regarding this prescription.
• Online consultations for PE are available but must be with licensed professionals.
• Be cautious of platforms that issue prescriptions after only a questionnaire.
• A legitimate online service will require a virtual consultation with a doctor.
• Ensure the online pharmacy is registered with the Spanish Council of Pharmacists.
• Read reviews and verify contact information before using an online service.
• Trust your instincts; if an offer seems too good to be true, it probably is.

[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.

About Tadalafil and Dapoxetine

The major product at the end of the metabolic pathway is circulating dapoxetine N-oxide, which is a weak SSRI and contributes no clinical effect. The metabolites of dapoxetine are eliminated rapidly in the urine with a terminal half-life of 18.7 and 21.9 hours for a single dose of 30 mg and 60 mg, respectively. The cardiovascular safety profile of dapoxetine has been studied extensively during the drug development. Phase I trials showed that dapoxetine had neither clinically significant electrocardiographic effects nor delayed repolarization effects, with dosing up to four-fold greater than the maximum recommended dosage, which is 60 mg. Phase III studies in men with PE showed a safety and well tolerated profile of dapoxetine with dosing of 30 and 60 mg. It has also been approved in France, Russia, Malaysia, Philippines, Argentina, and Uruguay.

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If a patient stops taking dapoxetine, he should wait for 7 days before receiving these drugs. The most common effects when taking dapoxetine are nausea, dizziness, dry mouth, headache, diarrhea, and insomnia. [16][17] Discontinuation rates due to adverse effects and costs are very high, as demonstrated in a study in Asia which showed that cumulative discontinuation rates within one year are as high as 87%. [18] Unlike other SSRIs used to treat depression, which have been associated with high incidences of sexual dysfunction,[19] dapoxetine is associated with low rates of sexual dysfunction. Taken as needed, dapoxetine has very mild adverse effects of decreased libido (<1%) and erectile dysfunction (<4%).

Brochure PRODUCT LIST OF PHARMA JITAI

No case of drug overdose has been reported during clinical trials. Many men who have PE also suffer from erectile dysfunction (ED). Treatment for these patients should consider the drug–drug interaction between dapoxetine and PDE5 inhibitors such as tadalafil (Cialis) or sildenafil (Viagra). In Dresser study (2006), plasma concentration of 24 subjects was obtained. Half of the sample pool were treated with dapoxetine 60 mg plus tadalafil 20 mg; the other half were treated with dapoxetine 60 mg plus sildenafil 100 mg. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).