English name

Dapoxetine

Latin name of the substance Dapoxetine

Dapoxetinum (genus Dapoxetini)

(S)-N,N-Dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine

Brutto formula

C₂₁H₂₃NO

Nosological classification

CAS code

119356-77-3

Pharmacological action

It is assumed that the mechanism of action of dapoxetine in premature ejaculation is associated with inhibition of serotonin reuptake by neurons, followed by an increase in the action of the neurotransmitter on pre- and postsynaptic receptors. The mechanism of ejaculation is mainly regulated by the sympathetic nervous system. Postganglionic sympathetic nerve fibers innervate the seminal vesicles, vas deferens, prostate, muscles of the urethra, and bladder neck, causing them to contract in a coordinated manner to achieve ejaculation. Dapoxetine affects the ejaculation reflex, increasing the latent period and reducing the duration of reflex impulsation of motoneurons of the ganglia of the perineum. The stimulus that triggers ejaculation is generated in the spinal reflex center, which is controlled through the brainstem by several nuclei of the brain, incl. preoptic and paraventricular.

Pharmacokinetics

Absorption. Dapoxetine is rapidly absorbed and C_max is reached 1-2 hours after ingestion. Absolute bioavailability is 42% (range 15-76%). After a single oral dose of dapoxetine on an empty stomach at doses of 30 and 60 mg, C_max of the substance in blood plasma is 297 ng / ml (after 1.01 h) and 498 ng / ml (after 1.27 h), respectively .

Fatty food moderately reduces C_max of dapoxetine (by 10%) and increases by 12% AUC and T_max in blood plasma, however, the degree of absorption of dapoxetine does not change — these changes are clinically insignificant. Dapoxetine can be taken with or without food.

Distribution. More than 99% of dapoxetine binds to plasma proteins in vitro. Active metabolite — desmethyldapoxetine — binds to plasma proteins by 98.5%. Dapoxetine is rapidly distributed throughout the body with an average V_ss 162 L When administered intravenously in humans, the average T_{1/2< /sub>} in the initial, intermediate and terminal phases of hatching is 0.1; 2.19 and 19.3 hours respectively.

Metabolism. Research in vitro suggest that dapoxetine is metabolized by many liver and kidney enzymes, especially CYP2D6, CYP3A4 and flavin-containing monooxygenase (FMO1) of the kidneys. In a clinical study investigating the metabolism of ¹⁴C-dapoxetine, dapoxetine was extensively metabolized after oral administration, mainly by N-oxidation, N-demethylation, naphtho group hydroxylation, glucuronidation, and addition of a sulfo group. After oral administration, signs of first pass metabolism in the liver were found. The main components circulating in blood plasma were intact dapoxetine and dapoxetine-N-oxide. In research in vitro found that dapoxetine-N-oxide is inactive. In addition, desmethyldapoxetine and didesmethyldapoxetine were detected in amounts less than 3% of the total amount of circulating dapoxetine metabolites. In the study, in vitro found that desmethyldapoxetine is comparable in activity to dapoxetine, and didesmethyldapoxetine is about 2 times less active than dapoxetine. Exposure (AUC and C_max) of unbound desmethyldapoxetine was 50 and 23% of unbound dapoxetine, respectively.

Excretion. Dapoxetine metabolites are excreted primarily in the urine as conjugates. Unchanged active substance in the urine is not detected. Dapoxetine is rapidly eliminated, as evidenced by a low plasma concentration (less than 5% of C_max) 24 hours after a dose. With daily intake, the accumulation of the substance in the body is minimal. Oral final T_1/2< /span> is approximately 19 hours.

Pharmacokinetics in special categories of patients

Race. A single dose of dapoxetine at a dose of 60 mg did not reveal a statistically significant difference between Europeans, blacks, Hispanics and Asians. Comparison of the pharmacokinetics of dapoxetine in Europeans and Japanese showed higher C_max and AUC in the latter (by 10 & ndash; 20%) due to lower body weight. A higher level of systemic exposure is unlikely to cause a significant difference in clinical effect.

Elderly patients (65 years and older). A single dose of dapoxetine at a dose of 60 mg did not reveal a significant difference in pharmacokinetic parameters (C_max, AUC< sub>0–∞, T_max) in healthy older men and younger men. Dapoxetine AUC_0–∞ Mean and Endpoint T_1/2 were 12% and 46% higher, respectively, in older men compared to younger men.

Impaired renal function. A single dose of dapoxetine at a dose of 60 mg showed no relationship between creatinine clearance and C_max or AUC_{0–&infin ;} dapoxetine in patients with mild (Cl creatinine 50 & ndash; 80 ml / ml), moderately pronounced (Cl creatinine from 30 to < 50 ml / min) and severe (Cl creatinine < 30 ml / min) impaired function kidneys. AUC of dapoxetine in patients with severe renal impairment was about 2 times higher than in patients with normal renal function. Data on the use of dapoxetine in patients with severe renal impairment are limited. In patients requiring hemodialysis, the pharmacokinetics of dapoxetine has not been studied.

Hepatic impairment. In patients with mild hepatic impairment, the pharmacokinetics of dapoxetine and desmethyldapoxetine did not change. In patients with moderate hepatic impairment (Child-Pugh class B) C_max and AUC of unbound dapoxetine increased by 55% and 120%, respectively. The C_max of the unbound active fraction of dapoxetine was unchanged, and the AUC — increased by 2 times.

In patients with severe hepatic impairment, C_max of unbound dapoxetine was not altered, a AUC of unbound dapoxetine was more than 3-fold increased. AUC of the active fraction was also increased several times.

CYP2D6 polymorphism. Plasma concentration of dapoxetine after a single dose of dapoxetine at a dose of 60 mg in patients with low CYP2D6 activity was higher than in patients with high CYP2D6 activity (C< sub>max by about 31%, AUC_0–∞ — by about 36%). Similarly, C_max of desmethyldapoxetine in patients with low CYP2D6 activity was increased by 98%, and AUC_0–∞ — by 161%. Medium End T_1/2 dapoxetine increased by 2.4 hours in patients with low activity of the CYP2D6 isoenzyme compared with patients with high activity of the CYP2D6 isoenzyme. C_max of the active fraction of dapoxetine is increased by approximately 46%, a AUC  — by about 90%. This increase may be accompanied by an increased frequency and severity of dose-related adverse events. The safety of the use of dapoxetine in patients with low CYP2D6 activity may be questionable when taking other drugs that can inhibit the metabolism of dapoxetine, in particular active and moderately active inhibitors of CYP3A4.

Dapoxetine and desmethyldapoxetine plasma concentrations are expected to be reduced in patients with ultra-high CYP2D6 activity.

Dapoxetine is indicated for the treatment of premature ejaculation in men aged 18 to 64.

Hypersensitivity to dapoxetine hydrochloride. Severe heart disease (such as heart failureII–IV class in NYHA, cardiac conduction disorders (block AV 2nd degree conduction or sick sinus syndrome) in the absence of a permanent pacemaker, severe coronary heart disease or valvular disease). Simultaneous use of MAO inhibitors and use within 14 days after stopping their use; similarly, MAO inhibitors should not be taken within 7 days of stopping dapoxetine. Simultaneous reception of thioridazine and within 14 days after the termination of its use; similarly, thioridazine should not be taken within 7 days of stopping dapoxetine. Simultaneous use of SSRIs, serotonin and norepinephrine reuptake inhibitors and tricyclic antidepressants and other drugs with serotonergic (e.g. L-tryptophan, triptans, tramadol, linezolid, lithium, St. Dapoxetine Concomitant administration with active inhibitors of CYP3A4, such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, atazanavir, etc. Moderately severe and severe liver dysfunction Severe renal dysfunction Children and adolescents under 18 years of age .

If there is a history of known or suspected orthostatic hypotension, or a history of mania/hypomania or bipolar disorder, treatment with dapoxetine should be avoided.

Mild to moderate renal dysfunction; simultaneous use with strong CYP2D6 isoenzyme inhibitors and moderate CYP3A4 inhibitors in patients with genotypically low activity of the CYP2D6 isoenzyme and patients with high activity of the CYP2D6 isoenzyme (in combination with moderate inhibitors of the CYP3A4 isoenzyme); simultaneous use with drugs that affect platelet aggregation, and with anticoagulants due to the risk of bleeding.

Dapoxetine is not intended for use in women.

Based on the limited data available from clinical trials, there is no evidence to suggest that the use of dapoxetine by a man can affect the pregnancy of his partner. Well-controlled studies of the use of dapoxetine in pregnant women have not been conducted.

It is not known whether dapoxetine and its metabolites are excreted in breast milk.

In clinical studies, the following side effects were reported, which were observed frequently and were dose-dependent: nausea (11 and 22.2% when taking 30 and 60 mg of dapoxetine, respectively), dizziness (5.8 and 10.9 %), headache (5.6 and 8.8%), diarrhea (3.5 and 6.9%), insomnia (2.1 and 3.9%), fatigue (2 and 4.1%). The most common events requiring discontinuation of treatment were nausea (in 2.2% of patients) and dizziness (1.2%).

The frequency of side effects is defined as very common (≥1/10); often (≥1/100<1/10); infrequently (≥1/1000<1/100); rarely (≥1/10000–<1/1000).

Mental disorders: often — anxiety, agitation, restlessness, unusual dreams, decreased libido; infrequently — depression, depressed mood, state of euphoria, mood swings, nervousness, indifference, apathy, confusion, disorientation, pathological thinking, somatosensory amplification, sleep disturbance, initial insomnia, intrasomnia disorder, nightmares, bruxism, loss of libido, anorgasmia.

Co withparts of the central nervous system: very often — dizziness, headache; often — drowsiness, impaired concentration, tremor, paresthesia; infrequently — fainting, incl. vasovagal, postural dizziness, akathisia, taste perversion, hypersomnia, lethargy, sedation, depression of consciousness; rarely — dizziness during physical exertion, sudden falling asleep.

On the part of the organs of vision: often — blurred vision; infrequently — mydriasis, eye pain, blurred vision.

On the part of the hearing organs and the labyrinth: often — tinnitus; infrequently — vertigo.

From the CCC side: often — flushes of blood; infrequently — cessation of sinus node activity, sinus bradycardia, tachycardia, decreased BP, systolic hypertension; rarely — hot flashes.

Respiratory: often — nasal congestion, yawning.

Gastrointestinal: very common — nausea; often — diarrhea, vomiting, constipation, abdominal pain, dyspepsia, flatulence, stomach discomfort, bloating, dry mouth.

Skin and subcutaneous tissues: often — hyperhidrosis; infrequently — itching, cold sweat.

On the part of the reproductive system: often — erectile dysfunction; infrequently — lack of ejaculation, orgasm disturbance, incl. anorgasmia in men, paresthesia of the genital organs of men.

General Status: often — weakness, irritability; infrequently — asthenia, a feeling of heat, a feeling of anxiety, a feeling of malaise, a feeling of intoxication.

Lab changes: often — increase in blood pressure; infrequently — increase HR, increase DABP, increase in orthostatic BP.

Description of individual side effects

Funning with loss of consciousness, with bradycardia, or sinus arrest has been observed in patients on Holter monitoring and has been reported in clinical trials. These adverse events were regarded as associated with the use of dapoxetine. Most cases were observed within the first 3 hours after taking dapoxetine, after taking the first dose, or associated with medical procedures (blood sampling, changes in body position, blood pressure measurement). Prodromal symptoms often preceded syncope. The incidence of syncope and prodromal symptoms was dose-dependent, which was demonstrated in patients receiving higher doses of dapoxetine.

Dapoxetine withdrawal effects

For sudden withdrawal of long-term SSRIs for the treatment of chronic depressive disorders the following symptoms were noted: dysphoria, irritability, agitation, dizziness, sensory disturbances (for example, paresthesia), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. The results of the safety study showed a higher frequency of withdrawal symptoms in the form of insomnia and mild to moderate dizziness after discontinuation of dapoxetine after 62 days of use.

MAO Inhibitors

In patients treated with SSRI and MAO, described serious, sometimes fatal reactions, incl. hyperthermia, rigidity, myoclonus, instability of the autonomic system with possible rapid fluctuations in vital signs, as well as changes in mental state, incl. great agitation progressing to delirium and coma. These reactions have also been observed in patients who recently discontinued SSRIs and started treatment with a MAO. In some cases, the symptoms resembled neuroleptic malignant syndrome. Data on the combined use of SSRIs and inhibitors MAO in animals suggest that these drugs may synergistically increase BP and cause behavioral arousal. Therefore, dapoxetine should not be taken simultaneously with inhibitors MAO and within 14 days after stopping their use. Similarly, MAO inhibitors should not be taken within 7 days of stopping dapoxetine.

Thioridazine

Thioridazine prolongs the QTc associated with ventricular arrhythmia. Drugs such as dapoxetine that inhibit the CYP2D6 enzyme appear to inhibit the metabolism of thioridazine. The resulting increase in thioridazine levels is expected to increase prolongation of the QTc. Dapoxetine should not be taken concomitantly with thioridazine and for 14 days after stopping its use. Similarly, thioridazine should not be taken within 7 days of stopping dapoxetine.

Drugs with serotonergic effects

As with SSRIs, Dapoxetine taken concurrently with serotonergic Drugs (including inhibitors MAO, L-tryptophan, triptans, tramadol, linezolid, SSRIs, serotonin and norepinephrine reuptake inhibitors, lithium, and St John's wort (Hypericum perforatum) may increase frequency Dapoxetine should not be taken concomitantly with other SSRIs, MAO and other serotonergic drugs and within 14 days after discontinuation of this their LS. Similarly, these drugs should not be taken within 7 days after stopping dapoxetine.

CNS-acting drugs

Dapoxetine taken simultaneously with drugs acting on CNS in patients with premature ejaculation has not been studied. It is recommended to exercise caution if it is necessary to take these drugs simultaneously.

Influence of other drugs on dapoxetine

Research using human liver, kidney and intestinal microsomes in vitro showed that dapoxetine is metabolized mainly by CYP2D6, CYP3A4 and FM01. Therefore, inhibitors of these enzymes can reduce the clearance of dapoxetine.

CYP3A4 inhibitors

Active CYP3A4 inhibitors. Ketoconazole 200mg 2 times a day for 7 days increased C_max and AUC_0∞ of dapoxetine (60 mg once) by 35 and 99%, respectively. Taking into account the proportion of unbound dapoxetine and desmethyldapoxetine, C_max of the active fraction (the sum of unbound dapoxetine and desmethyldapoxetine) in the presence of active inhibitors of CYP3A4 can increase by about 25%, a AUC can be doubled. This is an increase in C_max and AUC active fraction may be significantly more pronounced in the subpopulation of patients who do not have a functionally active CYP2D6 enzyme, as well as while taking active inhibitors of CYP2D6.

Dapoxetine should not be co-administered with active CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir and atazanavir.

Moderately active CYP3A4 inhibitors. Concomitant use of moderately active CYP3A4 inhibitors, such as erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, or diltiazem, may significantly increase systemic exposure dapoxetine and desmethyldapoxetine, especially in patients with low CYP2D6 activity. The maximum dose of dapoxetine taken simultaneously with these drugs should be limited to 30 mg and taken with caution.

Active CYP2D6 inhibitors

Dapoxetine 60 mg/day for 7 days increased C_max and AUC_0∞ of dapoxetine (60 mg single dose) by 50 and 88% respectively. Taking into account the proportion of unbound dapoxetine and desmethyldapoxetia, C_max of the active fraction (the sum of unbound dapoxetine and desmethyldapoxetine) in the presence of active inhibitors of CYP2D6 can increase by about 50%, and AUC can be doubled. This is an increase in C_max and AUC active fractions close to expected in patients with low CYP2D6 activity and may lead to an increase in the frequency and severity of dose-dependent adverse reactions. Therefore, caution is advised when increasing the dose of dapoxetine to 60 mg in patients receiving active CYP2D6 inhibitors and in patients with low CYP2D6 activity.

Drugs metabolized by CYP1A and CYP2B6 isoenzymes

Based on comparison of C_max of dapoxetine at 60 mg dose and dapoxetine concentration at 50% inhibition (IC₅₀) of the CYP1A2 isoenzyme in vitro concluded that no effect of dapoxetine on concentration is expected simultaneously prescribed drugs metabolized by this isoenzyme. The effect of dapoxetine on the CYP2B6 isoenzyme has not been studied.

PDE-5 Inhibitors

The pharmacokinetics of dapoxetine taken at a dose of 60 mg concomitantly with tadalafil (20 mg) or sildenafil (100 mg) has been studied. Tadalafil did not affect the pharmacokinetics of dapoxetine. Sildenafil slightly increased the AUC_0∞ and C_max of dapoxetine (by 22 and 4%, respectively), which is considered clinically insignificant. Dapoxetine should be used with caution in patients taking PDE-5 inhibitors due to the possible reduced tolerance of these patients to orthostatic hypotension.

The effect of dapoxetine hydrochloride on concomitantly taken drugs

Tamsulosin. Single and repeated administration of dapoxetine at doses of 30 and 60 mg to patients receiving tamsulosin daily did not lead to a change in the pharmacokinetics of the latter. At the same time, the frequency of orthostatic hypotension also did not change, which was the same when taking only tamsulosin and the combination of tamsulosin with dapoxetine 30 or 60 mg. Dapoxetine should be used with caution in patients taking alpha-blockers due to the possible reduced tolerance of these patients to orthostatic hypotension.

Drugs metabolized by CYP2D6

Multiple doses of dapoxetine (60 mg/day for 6 days) increased C_max and AUC_0∞ of desipramine (50 mg once) by 11% and 19%, respectively, compared with desipramine alone. Dapoxetine may similarly increase plasma concentrations of other drugs metabolized by CYP2D6. The clinical significance of this is likely to be low.

Drugs metabolized by CYP3A

Multiple doses of dapoxetine (60 mg/day for 6 days) reduced the AUC_0∞ of midazolam (8 mg single dose) by approximately 20% (range from −60 % to +18%). The clinical significance of this phenomenon in most patients is likely to be low. However, an increase in CYP3A activity may be of clinical importance in some patients who simultaneously take drugs metabolized mainly by CYP3A and have a narrow therapeutic window.

Drugs metabolized by CYP2C19

Multiple doses of dapoxetine (60 mg/day for 6 days) did not affect the pharmacokinetics of omeprazole (40 mg once). Dapoxetine is unlikely to affect the pharmacokinetics of other CYP2C19 substrates.

Drugs metabolized by CYP2C9

Multiple doses of dapoxetine (60 mg/day for 6 days) did not affect the pharmacokinetics and pharmacodynamics of glibenclamide (5 mg once). Dapoxetine is unlikely to affect the pharmacokinetics of other CYP2C9 substrates.

PDE-5 Inhibitors

According to the results of the study, dapoxetine (60 mg) did not affect the pharmacokinetics of tadalafil (20 mg) and sildenafil (100 mg).

Warfarin

There are no data on the effects of long-term use of warfarin concomitantly with dapoxetine. Caution is advised when prescribing dapoxetine to patients taking warfarin for a long time. In a pharmacokinetic study, multiple doses of dapoxetine (60 mg/day for 6 days) did not affect the pharmacokinetics and pharmacodynamics (PT and MHO) of warfarin (25 mg once).

Ethanol

A single dose of ethanol (0.5 g/kg or approximately 2 doses) did not affect the pharmacokinetics of dapoxetine (60 mg single dose) and vice versa. Co-administration of dapoxetine and ethanol increased drowsiness and significantly reduced the level of wakefulness as assessed by the patient. Ethanol alone and dapoxetine alone did not significantly alter cognitive performance measures (response rate in the digit recognition test and digit substitution test) compared with placebo, however, the combination of ethanol with dapoxetine statistically significantly changed these measures compared with ethanol alone. The simultaneous use of ethanol and dapoxetine increases the frequency and severity of adverse reactions such as dizziness, drowsiness, slow reflexes, change in judgment. The combination of alcohol with dapoxetine can also increase neurocardiogenic side effects, in particular the frequency of syncope, which increases the risk of accidental injury. Therefore, patients should be advised to refrain from drinking alcohol during treatment with dapoxetine.

No cases of overdose have been reported in clinical studies.

Dapoxetine up to 240 mg (two doses of 120 mg 3 hours apart) did not cause unexpected adverse events. In general, SSRIs overdose symptoms include serotonergic reactions, incl. drowsiness, gastrointestinal disorders (nausea, vomiting), tachycardia, tremor, agitation and dizziness.

Overdose should be treated with standard supportive care if necessary. Due to the significant binding of dapoxetine to plasma proteins and the large V_{d< /sub>} dapoxetine hydrochloride forced diuresis, dialysis, hemoperfusion and blood transfusion are unlikely to be effective. No specific antidote known.

By mouth Adult men 18 to 64 years of age: Recommended starting dose for all men — 30 mg, 1-3 hours before the intended sexual intercourse. With insufficient effect and good tolerance of the dose of 30 mg, it can be increased to 60 mg. The maximum recommended frequency of reception — 1 time per 24 hours

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While some consumers seek cheaper or generic options, the need for formal approval means navigating complex regulations. Those interested in dapoxetine often compare prices and evaluate reviews, weighing the long-term benefits against potential risks. Understanding the approval process is crucial for those looking to purchase this medication legally and safely in the USA.

Using Dapoxetine: Main Purposes

Dapoxetine is primarily known for addressing specific needs related to male health. This drug is sought after in various regions, including the USA, and is used for improving certain conditions to enhance quality of life. It is available in several forms, offering flexibility for users depending on their individual requirements.

The table below outlines the main purposes and features associated with this medication:

Many choose to order this drug online due to convenience and competitive price options. Generic and brand versions are both obtainable, often necessitating a prescription. It's important to review tadalafil and dapoxetine interactions, as combined usage might be considered for long-term plans. The term "tadalafilise" sometimes refers to synergies between these compounds, closely monitored by health professionals to manage effects safely and effectively.

Reading reviews can provide insights into user experiences and what to expect when undertaking this treatment. Considerations should include the purchase of dapoxetine without compromising health standards, being mindful of where and how to buy the drug, whether in 40mg or more conventional dosages. Referencing credible sources like Wikipedia can offer valuable details on the drug's background and development.

Combining Tadalafil and Dapoxetine Safely

The idea of using Tadalafil and Dapoxetine together is gaining attention for addressing specific medical needs. Both medications are known for distinct purposes, and using them in combination involves understanding their uses, side effects, and ensuring safe administration. Exploring the dynamics of these two drugs requires discussing their effects and how they interact when used in conjunction.

Tadalafil, known by its brand name Cialis, is primarily used to treat erectile dysfunction. Available in various dosages such as 40mg and 90mg, it is renowned for its effectiveness and long-term impact. Dapoxetine, on the other hand, generally prescribed as a 60mg dose, targets premature ejaculation. Before proceeding, users are advised to get a prescription to ensure medical approval for this combination therapy.

The combination can enhance the experience by maximizing benefits from both drugs, but potential side effects must be carefully considered. Common concerns include headache, digestive issues, and dizziness. Those interested should review medical guidelines to anticipate what effects they might encounter. Consulting medical reviews and professional opinions further informs on the appropriate generic or brand choices, ensuring a well-balanced approach.

In the USA, purchasing these medications requires a legitimate prescription. Online platforms offer various ways to order, sometimes presenting competitive prices. It's crucial to buy from reputable sources to avoid counterfeit products. Investigating price differences between generic and brand names helps in making cost-effective decisions.

To obtain Tadalafil and Dapoxetine without encountering issues, patients are urged to follow appropriate medical advice. Ensuring the safe use of these drugs involves being well-informed about terms of use and their potential interactions. As such, evaluating online resources like Wikipedia can expand one's understanding of these medications before making a purchase. Following proper channels guarantees the combination can be used safely and affordably.

Reviews of Dapoxetine and Tadalafil Combination

The combination of dapoxetine and tadalafil has attracted attention as a potential solution for men seeking comprehensive treatment for certain intimate concerns. This combo is increasingly becoming popular due to its purported benefits and effectiveness.

Effects and Usage
The blend of dapoxetine and tadalafil is primarily used to address issues related to timing and performance. Dapoxetine, often referred to as the brand name, is approved in various regions, including the USA. On the other hand, tadalafil is well-known for its long-term efficacy and is available in dosages like 40mg and 60mg. These drugs together can help users get the best from both brands without sacrificing quality.

Price and Accessibility
One of the main concerns when considering this combination is the price. Various online platforms offer cheap options for those looking to purchase the combination, making it accessible to a wider audience. Where it is available, a prescription is often required due to the nature of its effects on the body.

Potential Side Effects
Like most medications, the combination of dapoxetine and tadalafil comes with potential side effects. Common reactions might include mild nausea or headache, but these often resolve over time. It is crucial to consult with a healthcare provider to understand what effects to expect and how to order safely.

Consumer Reviews
Feedback from users indicates a positive reception of the dapoxetine and tadalafil combo. Many reviews highlight the drug's effectiveness for its intended use without causing significant disruptions to daily life. Users often describe the combination as a game-changer for long-term satisfaction. For more comprehensive insights, one can explore discussions on platforms like wikipedia.

Price Comparison for Dapoxetine 40mg 60mg

Discovering the most advantageous price for Dapoxetine, particularly the 40mg and 60mg variants, can be challenging. This involves evaluating different suppliers, considering the necessity of a prescription, and understanding both the branded and generic options available. Knowing where and how to purchase this medication effectively, whether with or without prescription, is crucial for users who seek it's long term effects in managing specific conditions.

An efficient way to determine the best purchase options is through a price comparison of various offers, including online and offline outlets. Exploring these differences can help users make informed decisions and find the most cost-effective solution tailored to their needs.

The prices vary between pharmacies and depend significantly on whether you choose a brand or generic option. It's essential to review and compare both user reviews and prescription requirements to make a well-informed decision, ensuring the purchase meets your expectations in terms of price and effect. Exploring options to buy online can often provide more competitive rates and ease of ordering.

When purchasing Dapoxetine, checking for regulatory approval and understanding the potential side effects and how it is used in conjunction with drugs like Tadalafil is important. Finding the right balance between cost, accessibility, and benefits can enhance the overall satisfaction and outcome for users.

General. Dapoxetine is only for men with premature ejaculation. The safety of use in men without premature ejaculation has not been established, there is no data on delayed ejaculation.

Using with narcotic drugs. Patients should be advised not to take dapoxetine with narcotic drugs. Co-administration of dapoxetine with drugs with serotonergic activity, such as ketamine, methylenedioxymethamphetamine (MDMA), and lysergic acid diethylamide (LSD), can lead to potentially serious reactions, including (but not limited to) arrhythmia, hyperthermia, and serotonin syndrome. Taking dapoxetine with sedatives such as opiates or benzodiazepines may increase drowsiness and dizziness.

Ethanol. The combination of dapoxetine with alcohol may increase the effect of the latter on CNS and neurocardiogenic side effects of alcohol, such as fainting, which increases the risk of accidental injury. Therefore, patients should be advised to refrain from drinking alcohol while taking dapoxetine.

Fainness. The frequency of syncope in clinical studies of dapoxetine depended on the category of patients and ranged from 0.06% (for a dose of 30 mg) to 0.23% (for a dose 60 mg) to 0.64% (for both doses together) in a study in healthy volunteers.

Dapoxetine-treated patients were more likely to experience prodromal symptoms, incl. nausea, dizziness/feeling light in the head and sweating. At a dose of dapoxetine 30 mg, the frequency of nausea was 11%, the frequency of dizziness — 5.8%, hyperhidrosis — 0.8%. At a dose of dapoxetine 60 mg, these figures were 21.2; 11.7 and 1.5% respectively. The frequency of syncope and possible prodromal symptoms was dose-dependent, as evidenced by higher rates in patients receiving higher doses than the maximum recommended daily dose of 60 mg.

Instances of syncope observed in clinical trials were considered to be vasovagal in nature. Most of these events occurred within the first 3 hours after the first dose or were associated with study procedures in the clinical setting (eg, taking a blood sample, standing up abruptly, measuring blood pressure). Possible prodromal symptoms, such as nausea, dizziness, feeling of lightness in the head, palpitations, asthenia, confusion and sweating, usually also occurred in the first 3 hours after taking dapoxetine and often preceded syncope. Patients should be informed that syncope with or without prodromal symptoms may develop at any time during treatment with dapoxetine. The clinician should educate the patient on the importance of sufficient fluid loading and on recognizing prodromal signs and symptoms to reduce the risk of serious injury in a fall due to loss of consciousness. If possible prodromal symptoms appear, the patient should immediately lie down so that the head is lower than the body, or sit down with the head between the knees and remain in this position until the symptoms disappear. If fainting or other effects from CNS occur, the patient should be warned to avoid potentially traumatic situations, including driving car and control of dangerous mechanisms. The combination of dapoxetine with alcohol intake may increase neurocardiogenic side effects, incl. fainting, which increases the risk of accidental injury; therefore, patients should be advised to refrain from drinking alcohol during treatment with dapoxetine.

Patients at risk of cardiovascular disease. Patients with cardiovascular disease did not participate in clinical studies of dapoxetine. Patients with organic diseases of the heart and blood vessels (for example, obstruction of the ejection of blood from the heart, valvular lesions, carotid artery stenosis, coronary artery atherosclerosis) have an increased risk of undesirable cardiovascular consequences of syncope of cardiac and other origin. However, there are currently insufficient data to determine whether this risk extends to vasovagal syncope in patients with cardiovascular disease.

Orthostatic hypotension. Cases of orthostatic hypotension have been reported in clinical studies. The doctor should inform the patient in advance that if possible complications appear,dromal symptoms, such as a feeling of lightness in the head immediately after standing up, one should immediately lie down so that the head is lower than the body, or sit down with the head between the knees and remain in this position until the symptoms disappear. In addition, it is necessary to inform the patient about the need to avoid getting up abruptly after prolonged lying or sitting. In addition, dapoxetine should be used with caution in patients taking vasodilators (eg, alpha-blockers, nitrates, PDE-5 inhibitors) due to the possible reduced tolerance of such patients to the orthostatic effects of dapoxetine.

Moderately active CYP3A4 inhibitors. When taking dapoxetine concomitantly with moderately active CYP3A4 inhibitors (erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem), the dose of dapoxetine should be reduced up to 30 mg, care must be taken.

Active CYP2D6 inhibitors. Caution is advised when increasing the dose of dapoxetine to 60 mg in patients receiving active CYP2D6 inhibitors and in patients with low CYP2D6 activity, as this may increase the level of systemic exposure to dapoxetine with a corresponding increase in the frequency and severity of dose-dependent adverse events.

Suicide/suicidal ideation. In short-term studies, antidepressants, including SSRIs, compared with placebo, increased the risk of suicide and suicidal ideation more strongly in children and adolescents with generalized depression and other psychiatric disorders. In adults older than 24 years, this effect was not found. In clinical studies of dapoxetine for the treatment of premature ejaculation, clear data on the relationship of suicidal thoughts with treatment have not been obtained.

Mania. Dapoxetine should not be taken by patients with a history of mania/hypomania or bipolar disorder; when symptoms of these diseases appear, dapoxetine should be discontinued.

Seizures. Due to the ability of SSRIs< /span> to lower the seizure threshold, dapoxetine should be avoided in patients with unstable epilepsy; if seizures occur, dapoxetine should be discontinued. Patients with controlled epilepsy require careful monitoring.

Children and adolescents under 18 years of age. Dapoxetine should not be taken by patients under 18 years of age.

Comorbid depression and psychiatric disorders. Patients with signs and symptoms of depression should be evaluated prior to initiating dapoxetine to rule out an undiagnosed depressive disorder. Dapoxetine should not be taken concomitantly with antidepressants, including SSRIs and serotonin and norepinephrine reuptake inhibitors. It is not recommended to stop treatment for depression or anxiety to start treatment with dapoxetine. Dapoxetine is not intended for the treatment of psychiatric disorders (eg schizophrenia or depression) and should not be taken by men with these conditions as an increase in depressive symptoms cannot be ruled out. Any disturbing thoughts or sensations should be reported to the doctor immediately and if signs and symptoms of depression appear during treatment, dapoxetine should be discontinued.

Bleeding. When using SSRIs described cases of bleeding. Caution is advised when taking dapoxetine concomitantly with drugs that affect platelet function (eg, atypical antipsychotics, phenothiazines, acetylsalicylic acid, NSAIDs , anticoagulants), as well as in patients with a history of bleeding or bleeding disorders.

Impaired renal function. Dapoxetine is not recommended for patients with severe renal impairment, caution should be exercised in patients with moderate and mild renal impairment.

Withdrawal. There is evidence that abrupt withdrawal SSRIs, long-term used to treat chronic depressive disorders, lead to the following symptoms: decreased mood, irritability, agitation, dizziness, sensory disturbances (eg.paresthesia in the form of a sensation of electric shock), anxiety, confusion, headache, lethargy, emotional instability, insomnia, hypomania.

In a clinical study conducted to evaluate the effect of withdrawal of dapoxetine after 62 days of administration at a dose of 60 mg (daily or on demand) in patients with premature ejaculation, no signs of withdrawal syndrome were detected. After switching patients to placebo after daily administration of dapoxetine, only minor withdrawal symptoms were found in the form of mild to moderate insomnia and dizziness. Similar results were obtained in another double-blind clinical study with a one-week period for evaluating the effects of withdrawal after 24 weeks of using dapoxetine at a dose of 30 or 60 mg as required.

Influence on the ability to drive a car and other mechanical means. When taking dapoxetine, cases of dizziness, impaired attention, fainting, blurred vision, drowsiness are described. Patients should be advised to avoid situations that could result in injury, including driving and operating dangerous machinery.

Pills are contraindicated in lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Summary of www.grls.rosminzdrav.ru, 2014.