Buy Dapoxetine Online Canada
Dapoxetine is a unique, short-acting, selective serotonin reuptake inhibitor (SSRI). It is clinically proven that the drug is effective in the treatment of premature ejaculation in men aged 18 years and older. Approximately from 27 to 34% of men of all age groups suffer from premature ejaculation, taking Dapoxetine prolongs the duration of sexual intercourse by 3-4 times.
Period of treatment with the drug Dapoxetine
Patients with cardiovascular diseases did not participate in clinical trials of the drug. Patients with organic diseases of the heart and blood vessels (for example, obstruction of blood ejection from the heart, valvular lesion, carotid stenosis, coronary artery atherosclerosis) increase the risk of undesirable cardiovascular effects of syncope of the heart and other origin. However, there is currently insufficient data to determine whether this risk extends to vaso-vagal syncope in patients with cardiovascular diseases.
Orthostatic hypotension.In clinical studies, cases of orthostatic hypotension are described. The doctor should inform the patient in advance that when possible prodromal symptoms appear, for example, a feeling of lightness in the head immediately after getting up, you should immediately lie down so that the head is lower than the body, or sit with your head down between your knees, and remain in this position until disappearance of symptoms. In addition, you need to inform the patient about the need to avoid a sharp rise after prolonged lying or sitting. In addition, the drug Dapoxetine should be used with caution in patients taking vasodilator drugs (for example, alpha-blockers, nitrates, PDE5 inhibitors), because of the possible reduced tolerance of such patients to the orthostatic effect of the drug.
Moderately active CYP3A4 inhibitors. When taking Dapoxetine along with moderately active CYP3A4 inhibitors (erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem), the dose should be reduced to 30 mg, caution should be exercised.
Active CYP2D6 inhibitors.It is recommended that caution be taken 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 of the drug with a corresponding increase in the frequency and severity of dose-related adverse events.
Suicide / suicidal thoughts.In short-term studies, antidepressants, including SSRIs, compared with placebo, increased the risk of suicide and the occurrence of suicidal thoughts in children and adolescents with generalized depression and other mental disorders. In adults older than 24 years, no such effect was found. In clinical studies of the drug Dapoxetine for the treatment of premature ejaculation, clear data on the connection of suicidal thoughts with treatment has not been received.
Mania.The drug Dapoxetine should not be taken in patients with a history of mania / hypomania or bipolar disorder, the symptoms of these diseases should be stopped.
Seizures.Due to the ability of the SSRIs to reduce the seizure threshold, dapoxetine should be prescribed to patients with unstable epilepsy; the drug should be discontinued when seizures occur. Patients with controlled epilepsy require careful monitoring.
Concomitant depression and mental disorders. If a patient has signs and symptoms of depression, prior to the use of the drug, Dapoxetine should be examined to rule out the presence of undiagnosed depressive disorder. Dapoxetine should not be taken simultaneously with antidepressants, including SSRIs and serotonin and norepinephrine reuptake inhibitors. It is not recommended to stop the treatment of depression or anxiety to start treatment with the drug Dapoxetine. Dapoxetine is not intended for the treatment of mental disorders (for example, schizophrenia or depression), it should not be taken by men with these diseases, because this can not be ruled out by the increased symptoms of depression. 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 withdrawn.
Bleeding. When using SSRIs, bleeding cases are described. It is recommended that you take caution when taking Dapoxetine along with drugs that affect platelet function (for example, atypical antipsychotics, phenothiazines, acetylsalicylic acid, NSAIDs, anticoagulants), as well as in patients with bleeding or bleeding disorders in history.
Renal dysfunction.Dapoxetine is not recommended for patients with severe renal dysfunction, patients with moderate and mild renal dysfunction should be cautious.
Withdrawal Syndrome.There is evidence that abrupt cancellation of SSRIs that have been long used for the treatment of chronic depressive disorders leads to the following symptoms: decrease in mood, irritability, agitation, dizziness, sensitivity disorders (for example, paresthesia in the form of an electric shock sensation), anxiety, confusion consciousness, headache, lethargy, emotional instability, insomnia, hypomania.
In a clinical study conducted to assess the effect of drug discontinuation of Dapoxetine after 62 days of dosing at a dose of 60 mg (daily or on demand) in patients with premature ejaculation, no signs of withdrawal syndrome were found. After transferring patients to placebo after daily intake of the drug Dapoxetine, only slight withdrawal symptoms were observed in the form of weak or moderately pronounced insomnia and dizziness. Similar results were obtained in another clinical study with double-blind control with a weekly period of evaluating the effects of withdrawal after 24 weeks of use of the drug in a dose of 30 mg or 60 mg according to need.
Interaction with MAO inhibitors.In patients who received both SSRIs and an MAO inhibitor, serious and sometimes fatal reactions have been described, including hyperthermia, rigidity, myoclonus, instability of the vegetative system with possible rapid fluctuations in the indices of vital functions, as well as changes in the mental state, including strong arousal, progressing to delirium and coma. These reactions were also observed in patients who recently discontinued SSRIs and started treatment with MAO inhibitors. In some cases, the symptoms resembled a neuroleptic malignant syndrome. Data on the combined use of SSRIs and MAO inhibitors in animals suggest that these drugs can synergistically increase blood pressure and cause behavioral arousal. Therefore, the drug Dapoxetine can not be taken simultaneously with MAO inhibitors and for 14 days after discontinuation. Similarly, MAO inhibitors should not be taken for 7 days after discontinuation of dapoxetine.
Interaction with thioridazine.Thioridazine prolongs the QTc interval, which is accompanied by ventricular arrhythmia. Dapoxetine-type drugs that inhibit the CYP2D6 enzyme appear to inhibit thioridazine metabolism. It is expected that the increase in thioridazine levels caused by this will increase the prolongation of the QTc interval. Dapoxetine should not be taken concurrently with thioridazine and for 14 days after discontinuation. Similarly, thioridazine should not be taken within 7 days after discontinuation of dapoxetine.
Drugs with a serotonergic effect.As in the case of SSRIs, taking Dapoxetine at the same time as serotonergic drugs (including MAO inhibitors, L-tryptophan, triptans, tramadol, linezolid, SSRIs, serotonin and noradrenaline capture inhibitors, and Zymptoracids, developers, and ZyoRs, lithium serotonin and noradrenaline, Zyu, and Zyvos, and Zyvos, and ZyoRes, noradrenaline, and Zyroxin, and ZyoRes, noradrenaline, and Zyroxin, and Zyozar, noradrenaline, and Zyrophagia, and Nymphocytes, Nominees, Serotonin, Zioux, Sidol, serotoninergia, Nomonosum, Niolysacin, Nomonosum, Norepinephrine, and Noradrenaline Nitrogen. increase the frequency of serotonergic side effects. Dapoxetine should not be taken simultaneously with other SSRIs, MAO inhibitors and other serotonergic drugs and for 14 days after discontinuing These drugs should be taken in a similar way, these drugs should not be taken within 7 days after discontinuation of the drug Dapoxetine.
Drugs acting on the CHC. Dapoxetine at the same time as drugs acting on the central nervous system has not been studied in patients with premature ejaculation. It is recommended that caution be taken when taking these drugs at the same time.
Effects of other drugs on dapoxetine hydrochloride.Studies using human microsomes of the liver, kidneys, and intestines have shown that dapoxetine is metabolized primarily by CYP2D6, CYP3A4, and flavin-containing monooxygenase 1 (FMO1). Therefore, inhibitors of these enzymes can reduce the clearance of dapoxetine.
Active inhibitors of CYP3A4.Ketoconazole intake in a dose of 200 mg 2 times a day for 7 days increased Cmax of dapoxetine (60 mg once) by 35% and 99%, respectively. Taking into account the proportion of unbound dapoxetine and desmethyldipoxetine, the Cmax of the active fraction (the amount of unbound dapoxetine and desmethydipoxetine) in the presence of active CYP3A4 inhibitors can increase by about 25%, and AUC can double. This increase in the Cmax and AUC of the active fraction may be significantly more pronounced in a subpopulation of patients who do not have the functionally active CYP2D6 enzyme, as well as with the simultaneous use of active CYP2D6 inhibitors.
The drug Dapoxetine should not be taken simultaneously with active inhibitors of CYP3A4, for example, ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir and atazanavir.
Moderately active CYP3A4 inhibitors.Simultaneous intake of moderately active CYP3A4 inhibitors, for example, erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, or diltiazem, can significantly increase the level of systemic exposure to dapoxetine and desparasipine, discontinued neoprotein, etc. The maximum dose of the drug dapoxetine taken simultaneously with these drugs should be limited to 30 mg and taken with caution.
Active CYP2D6 inhibitors.Taking fluoxetine at a dose of 60 mg per day for 7 days increased the Cmax of dapoxetine (60 mg once) by 50% and 88%, respectively. Taking into account the proportion of unbound dapoxetine and desmethyldapoxetine, the Cmax of the active fraction (the amount of unbound dapoxetine and desmethydipoxetine) in the presence of active CYP2D6 inhibitors can increase by about 50%, and AUC can double. This increase in the Cmax and AUC of the active fraction is close to that expected in patients with low CYP2D6 activity and may lead to an increase in the frequency and severity of dose-related adverse reactions. Therefore, caution is recommended when increasing the dose of Dapoxetine to 60 mg in patients receiving active CYP2D6 inhibitors, and in patients with low CYP2D6 activity.
Interaction with drugs metabolized by CYP1A and CYP 2B6 isoenzymes.Based on comparative data of Cmax of dapoxetine when taking a 60 mg dose of the drug and the concentration of dapoxetine at 50% inhibition (IC50) of the CYP1A2 isoenzyme, it is concluded that the effect of dapoxetine on the simultaneously administered drugs metabolized is not expected 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 simultaneously with tadalafil (20 mg) or sildenafil (100 mg) was studied. Tadalafil did not affect the pharmacokinetics of dapoxetine. Sildenafil slightly increased the Cmax of dapoxetine (22% and 4%, respectively), which is considered clinically insignificant. Dapoxetine should be prescribed with caution to patients taking PDE5 inhibitors, because of the possibly reduced tolerance of these patients to orthostatic hypotension.
The effect of dapoxetine on concurrently taking drugs. Tamsulosin.The single and repeated intake of the drug Dapoxetine in doses of 30 mg and 60 mg in patients receiving tamsulosin daily did not change the pharmacokinetics of the latter. It also did not change the frequency of orthostatic hypotension, which was the same when taking only tamsulosin and in combination with tamsulosin and Dapoxetine 30 mg or 60 mg. Dapoxetine should be prescribed with caution to patients taking alpha-blockers, because of the possibly reduced tolerance of these patients to orthostatic hypotension.
Drugs metabolized by CYP2D6.Repeated administration of the drug Dapoxetine (60 mg per day for 6 days) increased the Cmax of desipramine (50 mg once) by 11% and 19%, respectively, compared with taking only desipramine. Dapoxetine can likewise increase the concentration in plasma and other drugs metabolized by CYP2D6. The clinical significance of this is likely to be small.
CYP2C19 metabolized drugs.Multiple administration of dapoxetine (60 mg per 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.Repeated administration of the drug Dapoxetine (60 mg per day for 6 days) did not affect the pharmacokinetics and pharmacodynamics of glyburide (5 mg once). Dapoxetine is unlikely to affect the pharmacokinetics and other substrates of CYP2C9.
Warfarin.There is no data on the effects of long-term use of warfarin simultaneously with the drug Dapoxetine. It is recommended to exercise caution when prescribing Dapoxetine to patients who take warfarin for a long time. In the pharmacokinetic study, repeated administration of dapoxetine (60 mg per day for 6 days) did not affect the pharmacokinetics and pharmacodynamics (PV and MHO) of warfarin (25 mg once).
Ethanol (alcohol).A single dose of ethanol (0.5 g / kg, or about 2 doses) did not affect the pharmacokinetics of dapoxetine (60 mg once) and vice versa. Simultaneous administration of the drug Dapoxetine and ethanol (alcohol) increased drowsiness and significantly reduced wakefulness when evaluated by the patient. Taking only ethanol and only Dapoxetine did not significantly alter cognitive functions (reaction rate in the digit recognition test and the digit character replacement test) compared with placebo, however, the combination of ethanol with Dapoxetine statistically significantly changed these indicators compared to ethanol alone. The simultaneous use of ethanol and the drug Dapoxetine increases the frequency and severity of adverse reactions such as dizziness, drowsiness, slow reflexes, changes in judgment. The combination of alcohol with the drug Dapoxetine may also enhance neuro-cardiogenic side effects, in particular, the frequency of fainting, which increases the risk of accidental injury. Therefore, patients should be advised to refrain from taking alcohol during the period of treatment with Dapoxetine.
Therapy for premature ejaculation
Experimental and clinical studies have demonstrated the important role of serotonergic mechanisms in regulating the process of ejaculation. German experts use an integrated approach to the treatment of premature ejaculation, taking into account all the factors of the pathogenesis of this dysfunction. The ultimate goal of treating premature ejaculation is to enable the patient to control the duration of sexual intercourse. In addition to psychotherapy, behavioral therapy (learning how to control ejaculation) for the treatment of premature ejaculation, medical and surgical methods are used.
For systemic medical therapy for premature ejaculation, selective serotonin uptake inhibitors (SSRIs) are used to increase the concentration of this mediator. These drugs were originally intended for the treatment of depression, but a side effect of their action, manifested in an increase in the duration of sexual intercourse, served as the basis for the use of SSRIs in the treatment of premature ejaculation. A new drug of this pharmaceutical group dapoxetine (prilidzhi) is considered by andrologists as the best drug for the treatment of premature ejaculation at the present time. Dapoxetine has a pronounced therapeutic effect, increasing the duration of sexual intercourse by 2–4 times, does not require regular use, is rapidly eliminated from the body and is perfectly combined with medications that improve erection (Levitra, Viagra, Cialis).
For the correction of ejaculatory disorders, various methods of reducing the hypersensitivity of receptor structures are also used. In addition to the use of gels and sprays containing local anesthetics, the technique of injecting hyaluronic acid gel into the skin of the glans penis is used. Gel substance forms a layer that separates the surface layer of the skin from the nerve endings, which leads to a temporary decrease in the sensitivity of the glans penis and contributes to the lengthening of sexual intercourse. During the period of time during which the resorption of hyaluronic acid occurs, a new stable stereotype of prolonged sexual intercourse has time to form. Depending on the wishes of the patient, various types of gel are introduced that have a complete resorption period from 3 to 12 months.
Such an idea of forming a device for prolonged sexual intercourse in the period of a temporary decrease in the sensitivity of an organ also underlies the microsurgical operation of selective denervation of the glans penis. The method consists in the isolation, intersection and subsequent stitching of part of the sensory nerves of the penis. This leads to temporary anesthesia of the penis, which allows to increase the duration of sexual intercourse several times. A period of 4 to 6 months, during which, as a result of the reinnervation processes, the sensitivity of the penis is restored, is sufficient for this result to become stable.
Perform intervention requires special equipment and highly skilled surgeon - andrologist. In case of premature ejaculation, caused by a short frenulum of the penis, plastic surgery is performed to lengthen the frenulum - frenulotomy. Short bridle cut across and sew in the longitudinal direction, which increases its length.