Product Overview
Product Name
BYS Dapoxetine Hydrochloride Tablets 30mg*6 tablets
Product Specifications
30mg*6 tablets
Expiration Date
36 months
Main Raw Materials
Main Ingredients: Dapoxetine Hydrochloride Chemical Name: (+)-(S)-N,N-Dimethyl-(α)-[2-(1-naphthyloxy)ethyl]-benzylamine hydrochloride Molecular Formula: C21H23NO·HCl Molecular Weight: 341.88
Manufacturer
Guangzhou Baiyunshan Pharmaceutical Group Co., Ltd. Baiyunshan Pharmaceutical General Factory
Indications
This product is indicated for the treatment of premature ejaculation (PE) in males aged 18 to 64 years who meet all of the following criteria: • Intravaginal ejaculation latency time (IELT) less than 2 minutes; and • Persistent or recurrent ejaculation with minimal sexual stimulation before, during, or shortly after vaginal penetration and before sexual satisfaction; and • Significant personal distress or interpersonal impairment due to premature ejaculation (PE); and • Poor control over ejaculation; and • History of premature ejaculation in most sexual intercourse attempts in the past 6 months.
Dosage and Administration
Oral. The tablet should be swallowed whole. Patients are advised to take the drug with at least a full glass of water. Patients should try to avoid injuries caused by prodromal symptoms such as syncope or dizziness. The recommended first dose for all patients in adult males (18 to 64 years old) is 30 mg, which needs to be taken about 1 to 3 hours before sexual intercourse. 60 mg should not be used as the starting dose of treatment. If the effect after taking 30 mg is not satisfactory and there are no moderate or severe adverse reactions or prodromal symptoms indicating syncope, the dose can be increased to the maximum recommended dose of 60 mg. If the patient has an orthostatic reaction at the initial dose, the dose should not be increased to 60 mg (see [Precautions]). This product is not suitable for daily use and should only be taken when sexual intercourse is expected. The maximum recommended frequency of use is once every 24 hours. This product can be taken before or after meals (see [Pharmacokinetics]). If the doctor chooses this product to treat premature ejaculation, the risk and patient-reported benefits should be evaluated in the first 4 weeks of treatment with this drug, or the patient's risk-benefit balance should be evaluated after 6 treatment doses and a decision should be made whether to continue using this product for treatment. The efficacy and safety data of this product for use for more than 24 weeks are limited, and the continued clinical need and benefit-risk balance of this product need to be re-evaluated at least every six months.Elderly (65 years and older) The safety and efficacy of this product have not been evaluated in patients aged 65 years and older, mainly because the data on the use of this product in this population are extremely limited (see [Pharmacokinetics]). Children and adolescents This product is not for use in people under 18 years of age. Patients with renal impairment No dose adjustment is required for patients with mild or moderate renal impairment, but it should be taken with caution. This product is not recommended for patients with severe renal impairment (see [Pharmacokinetics]). Patients with hepatic impairment No dose adjustment is required for patients with mild hepatic impairment; this product is contraindicated for patients with moderate and severe hepatic impairment (Child-Pugh Class C) (see [Pharmacokinetics]). Known CYP2D6 poor metabolizers or patients treated with strong CYP2D6 inhibitors For patients known to be CYP 2D6 poor metabolizers and those treated with strong CYP 2D6 inhibitors, it is recommended to increase the dose to 60 mg with caution (see [Precautions], [Drug Interactions] and [Pharmacokinetics]). Concomitant use of strong CYP3A4 inhibitors is contraindicated in patients treated with moderate or strong CYP3A4 inhibitors. For patients treated with concomitant moderate CYP3A4 inhibitors, the dose should be limited to 30 mg and caution is recommended (see Contraindications, Drug Interactions, and Pharmacokinetics).
Adverse reactions
Syncope and orthostatic hypotension have been reported in clinical trials (see [Precautions]). The following most common dose-related adverse reactions were reported in Phase 3 clinical trials: nausea (11.0% and 22.2% in the 30mg and 60mg as needed dapoxetine groups, 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%) and fatigue (2.0% and 4.1%). The most common adverse events leading to discontinuation were nausea (2.2% of subjects treated with this product) and dizziness (1.2% of subjects treated with this product). In clinical trials, drug-related loss of consciousness, syncope characterized by bradycardia or sinus arrest, has been reported in patients wearing Holter monitors. Most cases occurred within 3 hours of dosing, after the first dose, or during study-related procedures performed in the clinic (such as blood draws, upright maneuvers, and blood pressure measurements). Prodromal symptoms often occur before syncope. (See [Precautions]). The reported incidence of possible prodromal symptoms such as nausea, dizziness, and sweating was higher in the EDTA group than in the placebo group. In Phase 3 clinical trials, the incidence was higher when patients were treated with doses higher than the recommended dose, demonstrating that the occurrence of syncope and possible prodromal symptoms was dose-dependent. Orthostatic hypotension has been reported in clinical trials (see [Precautions]).The frequency of syncope manifesting as loss of consciousness in the dapoxetine clinical development program varied depending on the population studied and ranged from 0.06% (30 mg) to 0.23% (60 mg) in subjects participating in the Phase 3 placebo-controlled clinical trials and up to 0.64% (all doses combined) in Phase 1 non-PE healthy volunteers. Other Special Populations Caution should be used when increasing the dose to 60 mg in patients taking strong CYP2D6 inhibitors or in patients known to be poor CYP2D6 metabolizers (see Precautions and Drug Interactions). Discontinuation Effects Abrupt discontinuation of long-term selective serotonin reuptake inhibitors (SSRIs) for the treatment of chronic depression has been reported to result in the following symptoms: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias), anxiety, confusion, headache, drowsiness, mood lability, insomnia, and hypomania. Results from the safety study showed a slightly higher incidence of withdrawal symptoms of mild or moderate insomnia and dizziness in subjects who switched to placebo after 62 days of daily dosing.
Contraindications
Dapoxetine should not be used in patients with known hypersensitivity to dapoxetine hydrochloride or any of the excipients. It should not be used in patients with significant cardiac pathology [e.g. heart failure (NYHA II-IV), grade 1 conduction abnormalities (e.g. atrioventricular block or sick sinus syndrome), severe ischemic heart disease, severe valvular heart disease, history of syncope]. It should not be used in patients with a history of mania or severe depression. It should not be used with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation of MAOI treatment. Similarly, MAOIs should not be used within 7 days of discontinuation of this product (see [Drug Interactions]). It should not be used with thioridazine or within 14 days of discontinuation of thioridazine treatment. Similarly, thioridazine should not be used within 7 days of discontinuation of this product (see [Drug Interactions]).This product should not be used with serotonin reuptake inhibitors [selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs)] or other drugs/herbal medicines with serotonergic effects [such as L-tryptophan, triptans, tramadol, linezolid, lithium, Hypericum perforatum extract (Hypericum wilfordii)] or within 14 days of stopping these drugs/herbal medicines. Similarly, these drugs/herbal medicines should not be used within 7 days of stopping this product (see [Drug Interactions]). This product is contraindicated in patients who are also taking strong cytochrome P450 3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nafinavir, and atazanavir. This product is contraindicated in patients with moderate and severe hepatic impairment.
Precautions
General Precautions This product is only used for male patients with premature ejaculation. The safety of this product in men who do not suffer from premature ejaculation is not clear, and there is no data on the effect of this product on delayed ejaculation in this population. Other forms of sexual dysfunction Before treatment, the doctor should carefully examine the patient for other forms of sexual dysfunction, including erectile dysfunction. Men with erectile dysfunction (ED) who are using PDE5 inhibitors should not use this product. (See [Drug Interactions]) Orthostatic hypotension Before starting treatment, the prescribing physician should conduct a careful physical examination of the patient, including a history of orthostatic events. Before starting treatment, an orthostatic response test (supine and standing blood pressure and pulse) should be performed. If a history of orthostatic response is confirmed or suspected, this product should be avoided. Orthostatic hypotension has been reported in clinical trials of the same product marketed overseas. The prescribing physician should inform the patient in advance that if possible prodromal symptoms occur (such as dizziness shortly after standing up), the patient should immediately lie down with the head lower than the rest of the body, or sit down and place the head between the knees until the symptoms disappear. Prescribers should also inform patients that they should not stand up quickly after lying down or sitting for a long time.
Suicide/suicidal thoughts Short-term studies in children and adolescents with major depression and other psychiatric disorders have found that antidepressants (including selective serotonin reuptake inhibitors) can increase the risk of suicidal thoughts and behaviors compared with placebo. Short-term studies have not confirmed that antidepressants can increase the risk of suicidal behavior in adults over 24 years old compared with placebo. In clinical trials of the same product for the treatment of premature ejaculation that are marketed overseas, no clear treatment-related suicidal tendencies or behaviors were assessed by the Columbia Suicide Assessment Classification Calculation Method (C-CASA), Montgomery Depression Rating Scale, or Beck Depression Inventory. Syncope This product may cause syncope or dizziness. Patients should be warned to avoid situations that may cause injury, including driving or operating dangerous machinery, and situations where the use of drugs may cause syncope or its prodromal symptoms (such as dizziness or lightheadedness) (see [Adverse Reactions]). Compared with placebo, patients treated with this product may experience prodromal symptoms such as nausea, dizziness/dizziness, and sweating more often.Syncope (characterized by loss of consciousness), bradycardia or sinus arrest observed by Holter monitoring in clinical trials of the same product marketed overseas are all considered to be vasovagal reflexes in terms of etiology. Most cases occur within 3 hours after administration, after the first dose, or in conjunction with research-related operations performed in the clinic (such as blood draws, upright movements, and blood pressure measurements). Possible prodromal symptoms such as nausea, dizziness, lightheadedness, palpitations, weakness, confusion, and sweating generally occur within 3 hours after administration, often before syncope. Patients must be aware that they may experience syncope (with or without prodromal symptoms) at any time during treatment with this product. Prescribing physicians should inform patients of the importance of maintaining adequate hydration and how to recognize prodromal symptoms and signs to reduce the possibility of serious injury caused by falls due to loss of consciousness. If a patient has possible prodromal symptoms, he or she should immediately lie down with the head lower than the rest of the body, or sit down and place the head between the knees until the symptoms disappear. At the same time, the patient 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 machinery. Patients with cardiovascular risk factors Subjects with underlying cardiovascular disease were not included in Phase III clinical trials. Patients with underlying organic cardiovascular disease (such as clear outflow tract obstruction, valvular heart disease, carotid artery stenosis, and coronary heart disease) have an increased risk of adverse cardiovascular reactions caused by syncope (cardiac syncope and syncope from other causes).There are insufficient data to determine whether this increased risk translates into a risk of vasovagal syncope in patients with underlying cardiovascular disease. Use of Recreational Drugs Advise patients not to use stimulant psychotropic drugs with tamoxifen. Psychotropic drugs with serotonergic activity, such as ketamine, MDMA, and lysergic acid diethylamide, may cause serious adverse reactions if used concomitantly with tamoxifen. These adverse reactions include, but are not limited to, cardiac arrhythmias, hyperthermia, and serotonin syndrome. Concomitant use of sedative psychotropic drugs, such as narcotics and benzodiazepines, may increase somnolence and dizziness. Alcohol Concomitant use of tamoxifen may increase alcohol-related neurocognitive effects and may also increase neurocardiovascular adverse reactions (such as syncope), thereby increasing the risk of unintentional injury; therefore, advise patients to avoid alcohol when using tamoxifen. Medications with vasodilatory properties This drug should be used with caution in patients taking medications with vasodilatory properties, such as alpha-adrenergic receptor antagonists and nitrates, as this may reduce orthostatic tolerance (see [Drug Interactions]).Moderate cytochrome P450 3A4 inhibitors: The dose of this product is limited to 30 mg and caution is recommended when using moderate cytochrome P450 3A4 inhibitors simultaneously, such as erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil and diltiazem (see [Drug Interactions]). Strong cytochrome P450 2D6 inhibitors: Patients taking strong cytochrome P450 2D6 inhibitors simultaneously, or increasing the dose to 60 mg in patients who are poor metabolizers of P450 2D6, should be used with caution as this may increase exposure levels and lead to a higher frequency and severity of dose-dependent adverse events (see [Drug Interactions]). Mania: This product should not be used in patients with a history of mania/hypomania or bipolar disorder, and should be discontinued in any patient who develops symptoms of these disorders. Epilepsy Since selective serotonin reuptake inhibitors may lower the threshold for seizures, this product should be discontinued in any patient who develops a seizure, and should be avoided in patients with unstable epilepsy. Patients whose epilepsy is controlled should be closely monitored. Use in children and adolescents under 18 years of age This product should not be used in people under 18 years of age. Men with depressive symptoms and signs should be evaluated before using this product to rule out undiagnosed depressive illness. Concomitant use of antidepressants, including selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, is prohibited.It is not recommended to interrupt treatment for depression and anxiety to use this product to treat premature ejaculation. This product is not for psychiatric disorders and should not be used in male patients with psychiatric disorders (such as schizophrenia) or patients with psychiatric disorders and depression because exacerbation of depression-related symptoms cannot be excluded. This may be a result of the underlying psychiatric disorder or may be a result of medication. Physicians should encourage patients to report any distressing thoughts or feelings at any time, and if depressive signs and symptoms worsen, use of this product should be discontinued. Bleeding Bleeding abnormalities have been reported during treatment with selective serotonin reuptake inhibitors. Patients should be cautious when using this product, especially those who are concomitantly taking drugs known to affect platelet function (such as atypical antipsychotics and phenothiazines, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs [NSAIDs], antiplatelet drugs) or anticoagulants (such as warfarin) and those with a history of bleeding or coagulation disorders.Renal impairment This product is not recommended for patients with severe renal impairment and should be used with caution in patients with mild or moderate renal impairment. Discontinuation effects It has been reported that abrupt discontinuation of long-term selective serotonin reuptake inhibitor treatment for chronic depression can lead to the following symptoms: anxious mood, irritability, excitement, dizziness, paresthesia (i.e., sensory confusion, such as electric shock perception), anxiety, confusion, headache, lethargy, emotional lability, insomnia and hypomania. However, a double-blind clinical trial conducted in subjects with premature ejaculation to evaluate the discontinuation effect of dapoxetine 60 mg once daily or as needed for 62 days showed only mild withdrawal symptoms, namely a slight increase in the incidence of mild or moderate insomnia and dizziness in patients who switched to placebo after once-daily treatment with this product. Consistent results were also obtained in a second double-blind clinical trial, which included a 24-week treatment period of 30 mg and 60 mg, as needed, followed by a 1-week discontinuation evaluation period. Eye disorders As with other SSRIs, use of this drug has been associated with some eye reactions, such as mydriasis and eye pain. This drug should be used with caution in patients with increased intraocular pressure or at risk for angle-closure glaucoma. Lactose intolerance Patients with the rare hereditary problem of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use this drug. Keep out of the reach of children.
Precautions for children
This product should not be used in people under 18 years of age.
Precautions for pregnancy and lactation
This product is not suitable for women. Pregnancy No evidence of teratogenicity, embryotoxicity, or fetotoxicity was found when rats or rabbits received up to 100 mg/kg (rats) or 75 mg/kg (rabbits). Based on the limited observational data currently available from the clinical trial database, there is no evidence that the use of dapoxetine will affect maternal pregnancy. There are currently no adequate and well-controlled studies in pregnant women. Lactation It is not clear whether dapoxetine or its metabolites can be excreted in human milk.
Precautions for the elderly
The safety and efficacy of this product in patients aged 65 years and above have not been evaluated, mainly because the data on the use of this product in this population are extremely limited. Analysis of a single-dose clinical pharmacology study using 60 mg of dapoxetine hydrochloride showed that there were no significant differences in pharmacokinetic parameters (Cmax, AUCinf, Tmax) between healthy elderly men and healthy young men.
Drug Interactions
Potential for Interactions with MAOIs Severe (sometimes fatal) reactions have been reported in patients taking a selective serotonin reuptake inhibitor plus a monoamine oxidase inhibitor (MAOI) concomitantly. These reactions include hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs and changes in mental status, including extreme excitement progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued a selective serotonin reuptake inhibitor and started treatment with a monoamine oxidase inhibitor. Some cases have presented features similar to neuroleptic malignant syndrome. Data from animal models of the combination of selective serotonin reuptake inhibitors and monoamine oxidase inhibitors suggest that these drugs may have synergistic effects in increasing blood pressure and inducing behavioral excitement. Therefore, this product should not be used in combination with a monoamine oxidase inhibitor or within 14 days of stopping treatment with a monoamine oxidase inhibitor. Similarly, monoamine oxidase inhibitors should not be used within 7 days of stopping this product (see [Contraindications]). Potential for interaction with thioridazine Thioridazine alone can prolong the QTc interval and is associated with serious ventricular arrhythmias. Some drugs that inhibit the cytochrome P450 2D6 isoenzyme, such as this product, can inhibit the metabolism of thioridazine and lead to increased thioridazine concentrations, which can increase the prolongation of the QTc interval. This product should not be used in combination with thioridazine or within 14 days of stopping thioridazine treatment. Similarly, thioridazine should not be used within 7 days of stopping this product (see [Contraindications]).Drugs/herbal medicines with serotonergic effects As with other selective serotonin reuptake inhibitors, the co-administration of tadalafil with drugs/herbal medicines with serotonergic effects (including monoamine oxidase inhibitors, L-tryptophan, triptans, tramadol, linezolid, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, lithium, and Hypericum perforatum (Hypericum wilfordii)) may result in the development of serotonergic effects. tadalafil should not be used with other selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or other drugs/herbal medicines with serotonergic effects or within 14 days of discontinuation of these drugs/herbal medicines. Similarly, these drugs/herbal medicines should not be used within 7 days of discontinuation of tadalafil (see Contraindications). Central Nervous System Active Drugs The co-administration of tadalafil with CNS active drugs (e.g., anticonvulsants, antidepressants, antipsychotics, anxiolytics, sedative-hypnotics) in patients with premature ejaculation has not been systematically evaluated. Therefore, if this product needs to be used concomitantly with such drugs, patients should be treated with caution.
Pharmacological action
Dapoxetine is a potent selective serotonin reuptake inhibitor (SSRI) with an IC50 of 1.12nM. Its main metabolites are equivalent to the original drug (such as demethyl dapoxetine (IC50 < 1.0nM) and dimethyl dapoxetine (IC50 = 2.0nM)) or weakly effective (such as dapoxetine, IC50 = 282nM). Human ejaculation is mainly mediated by the sympathetic nervous system. The reflex pathway of ejaculation originates from the spinal reflex center, which is mediated by the brainstem and is initially affected by many brain nuclei (medial preoptic nucleus and inferior paraventricular nucleus). The mechanism of action of dapoxetine in the treatment of premature ejaculation may be related to its inhibition of neuronal reuptake of serotonin, thereby enhancing the effect of neurotransmitters on pre- and postsynaptic receptors. In rats, dapoxetine inhibits the ejaculation drive reflex by acting at the supraspinal level, of which the lateral paragigantic nucleus (LPGi) is an essential brain structure. The postganglionic sympathetic nerve fibers that innervate the seminal vesicles, vas deferens, prostate, urethral bulb muscles and bladder neck can cause the above organs to contract in a coordinated manner to achieve ejaculation. Dapoxetine can regulate the ejaculation reflex in rats.
