What Is Dapoxetine Hydrochloride?

Dapoxetine hydrochloride tablets, this product is suitable for the treatment of male premature ejaculation (PE) patients aged 18 to 64 years who meet all of the following conditions: before, during or shortly after insertion of the penis, and before sexual satisfaction only due to extreme Small sexual stimuli are continuous or repeated ejaculations; and significant personal distress or interpersonal disturbances caused by premature ejaculation (PE); and poor ability to control ejaculation. ^[1] .

Drug Name: Dapoxetine Hydrochloride Tablets

Hanyu Pinyin: Yan Suan Da Bo Xi Ting Pian

Cautions for Dapoxetine Hydrochloride Tablets

This product can only be purchased with a prescription from a urologist or an andrologist.

Dapoxetine hydrochloride tablets ingredients

Main ingredients: Dapoxetine hydrochloride.
Chemical name: (+)-(S) -N, N-dimethyl-- [2- (1-naphthyloxy) ethyl] -benzylamine hydrochloride Chemical structural formula: http: // x1. webres.medlive.cn/drugref/ChemPreparationDetail/201509091157240914.png
Molecular formula: C ₂₁ H ₂₃ N0.HCL
Molecular weight: 341.88

Properties of Dapoxetine Hydrochloride Tablets

This product is a gray film-coated tablet that appears white or off-white after removing the coating.

Indications of dapoxetine hydrochloride tablets

This product is suitable for the treatment of premature ejaculation (PE) in men aged 18 to 64 who meet all of the following conditions:
Continuous or repetitive ejaculation due to minimal sexual stimulation before, during, or shortly after insertion of the penis, and before sexual satisfaction; and significant personal distress or interpersonal caused by premature ejaculation (PE) Barriers to communication; Poor ejaculation control.

Specifications of dapoxetine hydrochloride tablets

30mg, 60mg (as C ₂₁ H ₂₃ N0).

Dapoxetine hydrochloride tablets dosage

oral. The tablets should be swallowed whole. Patients are advised to take the medication with at least a full glass of water. Patients should try to avoid injuries caused by prodromal symptoms such as syncope or dizziness.
1.Adult male (18 to 64 years)
The recommended first dose for all patients is 30 mg, which needs to be taken about 1 to 3 hours before sex. If the effect is not satisfactory after taking 30mg and the side effects are still within the acceptable range, the dosage can be increased to the maximum recommended dose of 60mg. The recommended maximum dosage is once every 24 hours.
This product can be taken before or after a meal (see the Pharmacokinetics section).
If a doctor chooses this product for premature ejaculation, he should evaluate the risk and the patient's reported benefits in the first 4 weeks after using this drug, or evaluate the patient's risk-benefit balance after using 6 treatment doses and decide whether to continue using this product.
Seniors (65 and over)
The safety and efficacy of this product in a population of patients 65 years and older have not been evaluated. The main reason is that there is very limited data on the use of this product in this population (see the Pharmacokinetics section).
Children and adolescents This product is not intended for people under 18 years of age.
Patients with kidney injury Patients with mild or moderate kidney injury do not need to adjust the dosage when taking this product, but they should be taken with caution. This product is not recommended for patients with severe renal impairment (see Pharmacokinetics section).
Patients with liver injury Patients with mild liver injury do not need to adjust the dosage when taking this product; this product is prohibited for patients with moderate and severe liver injury (Child-pugh Class C) (see Pharmacokinetics section).

Adverse effects of dapoxetine hydrochloride tablets

The clinical trial data evaluated the safety of this product in 6081 patients who had premature ejaculation and participated in five double-blind, placebo-controlled clinical trials. Of these evaluated subjects, 4222 received This product was treated, of which 1615 patients received 30 mg of this product as needed, and 2607 patients received 60 mg of this product, either on demand or once a day.
Syncope (characterized by loss of consciousness) has been reported in clinical trials, and the event was considered drug-related. Most cases occur within 3 hours after dosing, after the first dosing or during research-related procedures performed in the clinic (columns such as blood draws, upright movements, and blood pressure measurements), often before syncope Prodromal symptoms.
Orthostatic hypotension has been reported in clinical trials. The most common (5%) adverse drug reactions in clinical trials include headache, dizziness, nausea, diarrhea, insomnia, and fatigue. The most common events leading to discontinuation included nausea (2.2% of subjects treated with this product) and dizziness (1.2% of subjects treated with this product).
Table 1 lists the incidence of adverse drug reactions in the subjects treated with this product in these trials> 1%.
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Taboxetine hydrochloride taboo

This product is forbidden to use in patients who are allergic to dapoxetine hydrochloride or any excipients.
This product is prohibited for use in patients with significant pathological conditions of the heart [eg heart failure (NYHA II-IV), conduction abnormalities not treated with a permanent pacemaker (grade 2 or 3 atrioventricular block or sick sinus synthesis Sign), obvious myocardial ischemia and valvular disease]
This product should not be used in conjunction with monoamine oxidase inhibitors (MAOIs) or within 14 days after treatment with monoamine oxidase inhibitors has ceased. Similarly, monoamine oxidase inhibitors cannot be used for 7 days after stopping Brigadiene (see Drug Interactions section).
This product should not be used in combination with thioridazine or within 14 days after cessation of thioridazine treatment. Similarly, thioridazine cannot be taken for 7 days after discontinuing Brigadiene (see Drug Interactions section).
This product is contraindicated when taking strong cytochrome P450 3A4, such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nafenavir, atazanavir, etc. Patient.
This product is prohibited for use in patients with moderate and severe liver damage.

Precautions for dapoxetine hydrochloride tablets

The use of Brilliant may cause syncope or dizziness.
-If the patient has a possible prodromal symptom, lie down immediately so that the head is lower than other parts of the body, or sit down and place the head between knees until the symptoms disappear.
Patients should be warned to avoid situations that may cause injury if syncope or other central nervous system (CNS) effects occur, including driving or operating dangerous machines.
Combining this product with alcohol may aggravate alcohol-related neurocognitive effects, and may also aggravate adverse reactions of the nervous system (such as syncope), and therefore increase the risk of accidental injury; therefore, patients are advised to avoid it when taking this product Taking alcohol.
See the instructions for details.

Dapoxetine hydrochloride tablets for pregnant and lactating women

Women are not suitable to use this product.
Pregnant rats or rabbits receiving this product receiving up to 100 mg / kg (rat) or 75 mg / kg (rabbit) have found no evidence of teratogenicity, embryotoxicity or fetal toxicity. Based on the limited observations currently available from the clinical trial database, there is no evidence that taking dapoxetine will affect the mother's pregnancy. A sufficient number of well-controlled studies in pregnant women have not yet been conducted.
Breastfeeding is not yet clear whether dapoxetine or its metabolites can be secreted in human milk.

Dapoxetine hydrochloride tablets for children

This product should not be used by persons under 18 years of age.

Dapoxetine hydrochloride tablets for elderly

The safety and efficacy of this product in a population of patients 65 years and older have not been evaluated, mainly due to the extremely limited data on the use of this product in this population.
Analysis of a single-dose clinical pharmacological study using 60 mg of dapoxetine hydrochloride showed that there was no significant difference in pharmacokinetic parameters (Cmax, AUCinf, Tmax) between healthy elderly men and healthy young men.

Drug interactions of dapoxetine hydrochloride tablets

Possibility of interaction with monoamine oxidase inhibitor oxidase. Patients who have taken a selective serotonin reuptake inhibitor plus a monoamine oxidase inhibitor (MAOI) have had severe (sometimes fatal) reactions. Reported that these reactions include high fever, tonicity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs and changes in mental state, including quarterly excitement and development into delirium and coma. These reactions have also been reported in patients with serotonin reuptake inhibitors who have started treatment with a monoamine oxidase inhibitor, and some cases have characteristics similar to neuroblocker malignant syndrome. Hahahahahahaha 1.The possibility of interactions with monoamine oxidase inhibitors has been severe in patients who are taking a selective serotonin reuptake inhibitor plus a monoamine oxidase inhibitor (MAOI) at the same time (sometimes Reports of fatal) reactions including high fever, tonicity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs and changes in mental state, including extreme excitement and development into delirium and coma. These reactions have also been reported in patients who recently discontinued a selective serotonin reuptake inhibitor and started using a monoamine oxidase inhibitor. Some cases show characteristics similar to neuromuscular blocker malignant syndrome. The combination of selective serotonin reuptake inhibitors and monoamine oxidase inhibitors in animal models has shown that these drugs may have a synergistic effect in increasing hypertension and inducing behavioral excitement. Therefore, this product cannot be used in combination with monoamine oxidase inhibitors. Nor should it be used within 14 days of discontinuation of monoamine oxidase inhibitors. Similarly, monoamine oxidase inhibitors cannot be used within 7 days of discontinuation of this product. (See contraindications)

2. Possibility of interaction with thioridazine thioridazine alone can prolong the QTc interval, which is accompanied by severe ventricular arrhythmias. Some drugs that can inhibit the cytochrome P450 2D6 isoenzymes, such as Bilegen, can inhibit the metabolism of thioridazine and lead to an increase in the concentration of thioridazine, which will increase the prolongation of the QTc interval.
This product cannot be combined with thioridazine, nor can it be used within 14 days of discontinuation of thioridazine. Similarly, thioridazine cannot be used within 7 days of discontinuation of this product. (See contraindications)
3. Drugs / herbs with serotonin effects, like other selective serotonin reuptake inhibitors, will be beneficial to drugs / herbs with serotonin effects (including monoamine oxidase inhibitors, L-tryptophan, koji Protan, tramadol, linezolid, selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, lithium agent and St. John's wort extract (Hypericum) are possible in combination Will cause the serotonin effect. This product cannot be used in combination with other selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or other drugs / herbs with serotonin-related effects. Nor can they be used within 14 days of discontinuation of these drugs / herbs. Similarly, these drugs / herbs cannot be taken within 7 days of discontinuation of this product. (See contraindications)
Central nervous system active drugs have not been systematically evaluated for the combination of this product with CNS active drugs in patients with premature ejaculation. Therefore, if this product is required to be used concomitantly, patients should be treated with caution.
Effects of combination drugs on dapoxetine In vitro studies performed in human liver, kidney and intestinal microparticles show that dapoxetine is mainly produced by cytochrome P450 2D6, cytochrome P450 3A4 and flavin monooxygenase 1 (FMO1) Metabolism, so inhibitors of these enzymes may reduce the clearance of dapoxetine.
Ketoconazole, a potent cytochrome P450 3A4 inhibitor (200 mg twice daily for 7 days), increased CMAX and AUCINF of dapoxetine (60 mg single dose) by 35% and 99%, respectively. Considering the effect of free dapoxetine and desmethyl dapoxetine, if taking a strong inhibitor of CYP3A4, the maximum blood amount of the active part (the sum of free dapoxetine and desmethyl dapoxetine) The concentration may increase by about 25%, and the AUC may double. Such an increase may be obvious in some patients, mainly including the lack of a cytochrome CYP2D6 functional enzyme, that is, a weak metabolizer of cytochrome CYP2D6 or a strong combination of cytochrome P2D6. Patients with inhibitors.
Therefore, this product is contraindicated in patients taking ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nafenavir, atazanavir and other patients.
Moderate Cytochrome P450 3A4 Inhibitors Take moderate cytochrome P450 3A4 inhibitors at the same time as erythromycin, clarithromycin, fluconazole, amlunavir, furasanavir, aprepitant, verapamil M and diltiazem may also increase exposure to dapoxetine and desmethyl dapoxetine, especially those with weak cytochrome CYP2D6 metabolism. Therefore, in combination with any of the above drugs, the maximum dose of this product is limited to 30mg, and caution is recommended.

Dapoxetine hydrochloride tablets overdose

No overdose was reported during clinical trials. In clinical pharmacological studies of this product administered at a maximum of 240 mg daily (120 mg twice, with an interval of 3 hours), there were no unexpected adverse events. In general, symptoms of overdose of a selective serotonin reuptake inhibitor include serotonin-mediated adverse reactions such as drowsiness, gastrointestinal dysfunction such as nausea and vomiting, tachycardia, tremor, excitement and dizziness. In the case of overdose, standard support measures should be taken as needed. Due to the higher protein binding and larger distribution volume of dapoxetine hydrochloride, intensive diuresis, dialysis, blood perfusion, and blood exchange therapy are unlikely to be effective. There is currently no specific antidote for this product.

Clinical trial of dapoxetine hydrochloride tablets

The efficacy of this product in the treatment of premature ejaculation has been demonstrated in five double-blind, placebo-controlled clinical trials. A total of 6081 random subjects were included in the five trials. Subjects were 18 years of age and older, and premature ejaculation occurred in most of their sexual lives during the 6 months before enrollment. In four of these studies, subjects had a vaginal incubation latency (IELT: time from vaginal insertion to vaginal ejaculation) of at least 75% of evaluable sexual life events within the baseline period of <2 minutes. In the fifth study, the subjects' enrollment criteria were the same, however, no stopwatch was used to measure IELT. All studies excluded subjects with other forms of sexual dysfunction, including erectile dysfunction, or who were being treated with other forms of medication for premature ejaculation. In four of these studies, a stopwatch was used to measure the primary endpoint (mean intravaginal ejaculation latency) in a demagnetized life. The results of all randomized studies are consistent. In a representative study with the longest treatment time (24 weeks), a total of 1162 subjects were randomized, of which 385 patients received placebo and 386 patients received 30mg of this product as needed. 389 patients were required to receive a dose of 60 mg. Figure 1 shows the mean intravaginal ejaculation latency at baseline and at the end of the study for all treatment groups. Compared with the placebo group, the two treatment doses of this product had significant statistically significant increase in the latency of intravaginal ejaculation at the end of 24 weeks (p <0.001). The magnitude of the increase in the latency of vaginal ejaculation is related to the baseline latency of vaginal ejaculation, and the degree varies with different subjects. The clinical response of this product is described in the following patient reported remission rates.
In addition to the primary endpoint (mean intravaginal ejaculation latency), a definition of treatment response was used to demonstrate meaningful treatment benefit to the patient in the above study, which included a minimum of 2 points in controlling ejaculation and a reduction in ejaculation distress 1 point. The percentage of subjects who experienced remission in each group from week 4 to 24 weeks included was significantly higher than the placebo group (dapoxetine 30mg at week 16 compared with placebo p = 0.003, all others Compare p-values 0.001). A significant reduction in subject distress and a significant increase in subject satisfaction with sexual life were also observed.
Table 3 lists the improvement of the primary secondary endpoint at weeks 12 and 24.
The p-value of this product compared to placebo is less than 0.001: LPOCF refers to the carry-over observed after the last baseline. Other secondary reported results (PRO) endpoints evaluated in clinical trials include changes in clinical composite impression (CGIC, patient A common method of assessing your condition). Researchers have asked patients to compare premature ejaculation from the beginning of the study, and the options for remission have improved from drastically improved to significantly worsened. When the significance level was set to 0.05 (two cases) for testing, the endpoint of the clinical composite impression showed a statistically significant improvement over the placebo group. Table 4 presents the overall clinical impression results reported at the end of the above study by treatment group.
In a 12-week, Asia-Pacific study, 1067 subjects were randomly divided into 357 in the placebo group, 354 in the 30 mg on-demand treatment group, and 356 in 60 mg on-demand treatment group. Figure 2 shows the average IELT values at baseline and study endpoints across all treatment groups. Compared with the placebo group, the mean IELT at the 12-week end point (LPOCF) was significantly increased in the two treatment groups (p <0.001).
In addition to the primary endpoint mean IELT, there is also a data response to demonstrate the meaningful therapeutic benefit to the patient in the R096769-PRE-3003 study. This treatment response is controlled by ejaculation with at least 2 classifications and increased ejaculation-related pain Composed of falling classifications. From the time of the first dose measurement of IELT to week 12 (including week 12), the percentage of responding patients in each product group was significantly higher than that in the placebo group (p <0.001). Patients' pain decreased significantly and sexual intercourse satisfaction improved significantly. Table 5 shows the improvement of each key secondary endpoint at the 12-week end point.
The R096769-PRE-3003 study also evaluated other secondary patient-reported endpoint results (PRO), including changes in clinical comprehensive impressions (CGIC), a universal test used to evaluate patients' status. Patients were asked to compare premature ejaculation from the beginning of the trial. A choice was made between substantial improvement and substantial deterioration, with a statistically significant improvement in the CGIC endpoint compared to placebo, with a significant level of 0.05 (both sides). Table 6 shows the CGIC results reported in the last treatment group of the R096769-PRE-3003 study.
A placebo-controlled, double-blind, parallel grouping study evaluated the withdrawal effect of 60mg of this product on a long-term daily and timely basis to treat premature ejaculation. The study randomized 1,238 subjects. Subjects received daily or dark blood for 62 days of placebo or 60mg of this product, followed by a 7-day discontinuation evaluation period, during which subjects continued to receive this product or placebo. Signs and symptoms (DESS, a method prescribed by a physician to discontinue treatment with serotonin reuptake inhibitors) from discontinuation of medication are used to determine the effect of discontinuation after abrupt discontinuation of treatment. For each subject, the definition of withdrawal syndrome is determined weekly from day 63 to day 70

Pharmacology and toxicology of dapoxetine hydrochloride tablets

The mechanism of dapoxetine in the treatment of premature ejaculation may be related to its inhibition of serotonin reabsorption by neurons, which may affect the potential difference of neurotransmitters acting on pre-synaptic receptors of cells.
Human ejaculation is mainly mediated by the sympathetic nervous system. The reflex pathway of ejaculation comes from the spinal cord reflex center, which is mediated by the brain stem, and this reflex center is initially affected by many brain nuclei (medial preoptic nucleus and paraventricular nucleus). In rats, dapoxetine suppresses ejaculation-driven reflexes by acting on the spine level, in which the lateral giant cell nucleus (LPGi) is a necessary brain structure. The postganglionic sympathetic nerve fibers that dominate the seminal vesicles, vas deferens, prostate, urethral ball muscles, and bladder neck can cause the aforementioned organs to contract in concert to achieve ejaculation. Dapoxetine can modulate this ejaculation reflex in rats, thereby prolonging the incubation period of the genital motor neuron reflex discharge (PMRD) and reducing the duration of PMRD.
Toxicological effects:
In a rat oral administration test, dapoxetine was administered daily at a dose of up to 225 mg / kg / day and remained non-cancer resistant for about two years. The exposure resulting from this dose was about The recommended human dose (MRHD) of 60MG was twice the observed exposure (AUC) in men. In TG.rasH mice, dapoxetine was administered at a maximum possible dose of 100 mg / kg for 6 months and a dose of 200 mg / kg for 4 months did not cause tumors, for 6 consecutive months daily The steady-state exposure of 100 mg per kg of mice was less than that of a single clinical dose of 60 mg.
Tg.AC transgenic mice are topically administered daily at a dose of 375, 750 or 1500 mg / kg / day for 6 months and some tumor initiations can be observed at 750 mg / kg / day or higher dose levels after 6 months Sexual activity (papilloma at the site of administration). The systemic drug exposure calculated based on the AUC of Dapoxetine and major human metabolism is approximately 1 to 2 times the exposure observed in men receiving the maximum human recommended dose (MRHD) of 60 mg. The local exposure model is not suitable for oral administration. Drugs of medicine.
Neither dapoxetine nor its major human metabolites are mutagenic in in vitro bacterial Ames analysis or in forward mutation tests in mouse lymphocytes. In vitro chromosome aberration tests in Chinese hamster ovary cells or In vitro micronucleus analysis of mice, dapoxetine was not teratogenic.

Pharmacokinetics of dapoxetine hydrochloride tablets

1. Absorption After oral administration, dapoxetine is rapidly absorbed, reaching the maximum plasma concentration (Cmax) after approximately 1-2 hours. The absolute bioavailability is 42% (range 15-76%). After a single oral administration of 30 mg and 60 mg dapoxetine in the fasting state, peak plasma concentrations were reached after 1.01 and 1.27 hours (297 ng / ml and 498 ng / ml, respectively). Intake of a high-fat diet can moderately decrease the Cmax (10%) and increase AUC (12%) of dapoxetine, and at the same time, it can slightly delay the time to reach the peak concentration of dapoxetine; however, high-fat intake Diet does not affect the extent of absorption. None of these changes have clinical significance. Brilliant can be taken with or without meals. 2. Distributed in vitro, more than 99% of dapoxetine can be combined with human serum proteins. The protein-binding rate of the active metabolite desmethyldoxetine was 98.5%. Dapoxetine can be rapidly distributed with an average steady-state volume of distribution of 162 L. After intravenous administration in humans, the estimated average half-life of dapoxetine is 0.10, 2.19, and 19.3 hours, respectively. 3. Metabolic in vitro studies show that dapoxetine can be cleared by multiple enzyme systems in the liver and kidneys, mainly cytochrome P450 2D6, cytochrome P450 3A4, and flavin-containing monooxygenase 1 (FMO1). In a clinical study to observe the metabolism of 14C-dapoxetine, dapoxetine was extensively metabolized into a variety of metabolites after oral administration, mainly through the following biological transformation pathways: N-terminal oxidation, N-terminal demethylation , Naphthyl hydroxylation, glucosidation and sulfate. There is evidence of first pass metabolism before absorption into the blood after oral administration. Intact dapoxetine and dapoxetine-N-oxide are the major circulating forms in the plasma. Other metabolites include desmethyl dapoxetine, which has the same activity as dapoxetine, and bis demethyl dapoxetine is about 50% more active than dapoxetine. Considering viability and plasma unbound concentration, only demethyl dapoxetine increases the activity of dapoxetine in the body. 4. Excretion of metabolites of dapoxetine is mainly cleared from urine by the conjugate situation. No prototype active substance was detected in the urine. Dapoxetine can be quickly cleared, and the evidence is the bottom blood concentration (less than 5% of the peak concentration) at 24 hours after administration. Daily accumulation of dapoxetine medications is very small. The terminal half-life of oral administration is approximately 19 hours. The half-life of desmethyloxpoxetine is similar to that of daxoxetine.

Storage of dapoxetine hydrochloride tablets

Store at room temperature.

Packaging of dapoxetine hydrochloride tablets

30 mg * 3 tablets / box.

Expiry date of dapoxetine hydrochloride tablets

36 months

Dapoxetine Hydrochloride Tablets

JX20090323