Active substanceDapoxetineDapoxetine Similar drugsTo uncover Priligi® pills inwards Berlin-Chemie, AG Germany Primaxetine® pills inwards OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia Dosage form: & nbspFilm-coated tablets. Composition:1 tablet contains:active substance: dapoxetine hydrochloride 33.6 mg / 67.2 mg in terms of dapoxetine 30/60 mg;Excipients: lactose monohydrate 43.88 mg / 87.76 mg, microcrystalline cellulose 16.12 mg / 32.24 mg, croscarmellose sodium 4.0 mg / 8.0 mg, silicon dioxide colloidal anhydrous 1.0 mg / 2.0 mg, magnesium stearate 1.4 mg / 2.8 mg; excipients for the shell [hypromellose (hydroxypropylmethylcellulose) 2.1 mg / 4.2 mg, macrogol 6000 (polyethylene glycol 6000) 0.33 mg / 0.66 mg, titanium dioxide 0.559 mg / 1.098 mg, iron oxide black 0.01 mg / 0 , 04 mg, iron oxide yellow 0.001 mg / 0.002 mg]. Description:Round biconvex tablets covered with a film coat of gray color. On the cross section, the nucleus is white or almost white in color. Pharmacotherapeutic group:Remedy for premature ejaculation. ATX: & nbspG.04.B.X.14 DapoxetineG.04.B.X Other drugs for the treatment of urological diseases Pharmacodynamics:It is assumed that the mechanism of action of dapoxetine in premature ejaculation is associated with inhibition of reuptake of serotonin by neurons, followed by an increase in the action of the neurotransmitter on pre- and postsynaptic receptors.The mechanism of ejaculation is regulated mainly by the sympathetic nervous system. Postganglionic sympathetic nerve fibers innervate the seminal vesicles, the vas deferens, the prostate, the urethra and the neck of the bladder, causing their coordinated contraction to achieve ejaculation. Dapoxetine affects the ejaculation reflex, increasing the latent period and decreasing the duration of the reflex impulse of the motoneurons of the perineal ganglia. Stimulus, which starts ejaculation, is generated in the spinal reflex center, which is controlled through the brain stem by several nuclei of the brain, including the preoptic and paraventricular. Pharmacokinetics:SuctionDapoxetine is rapidly absorbed, and the maximum concentration in the blood plasma (Cmax) is reached 1-2 hours after taking the drug. Absolute bioavailability is 42% (range 15-76%). After a single oral administration of fasting dapoxetine at doses of 30 mg and 60 mg, the maximum plasma concentration of the substance is 297 ng / ml (after 1.01 hours) and 498 ng / ml (after 1.27 hours), respectively.The intake of fatty food moderately reduces C max dapoxetine (by 10%) and increases the AUC (area under the concentration-time curve) by 12% and the time to reach the maximum concentration in the blood plasma. However, the degree of absorption of dapoxetine remains unchanged. These changes are not clinically significant. The drug Primaxetine ® can be taken regardless of food intake.DistributionMore than 99% of dapoxetine binds to plasma proteins in vitro. The active metabolite, desmethyldapoxetine, binds to plasma proteins by 98.5%. Dapoxetine quickly distributed throughout the body with an average equilibrium volume of distribution of 162 liters. With intravenous administration in humans, the mean elimination half-life in the initial, intermediate and terminal elimination phases is 0.10, 2.19 and 19.3 hours, respectively.MetabolismIn vitro studies suggest that dapoxetine is metabolized by many enzymes of the liver and kidneys, especially CYP2D6, CYP3A4 and flavin-containing monooxygenase (FM01) kidney. In a clinical study in which metabolism was studied 14FROM -dapoxetine, dapoxetine after oral administration, was actively metabolized mainly by N-oxidation, N-demethylation, hydroxylation of the naphtho group, glucuronization and addition of the sulfo group.After oral administration, signs of a pre-systemic metabolism in the liver were found. The main components circulating in the blood plasma were intact dapoxetine and dapoxetine N-oxide. In in vitro studies, it has been found that dapoxetine-N-oxide is inactive. In addition, desmethyldapoxetine and didezmethyldapoxetine were detected in an amount of less than 3% of the total number of circulating metabolites of dapoxetine. An in vitro study found that desmethyldapoxetine is comparable in activity to dapoxetine, and didezmethyldapoxetine is about 2 times less active than dapoxetine. Exposure (AUC and Cmax) of unbound desmethyldapoxetine was 50% and 23% of unbound dapoxetine, respectively. ExcretionMetabolites of dapoxetine are excreted mainly with urine in the form of conjugates. An unchanged active substance in the urine is not detected. Dapoxetine is rapidly excreted, as evidenced by a low concentration of the substance in the blood plasma (less than 5% of the maximum) 24 hours after the dose. With daily intake of accumulation of matter in the body is minimal. When taken orally, the final elimination half-life is approximately 19 hours.Special patient groups RaceA single dose of dapoxetine in a dose of 60 mg did not reveal a statistically significant difference in the indices of Europeans, Negro people, Hispanics and people of the Asian race. Comparison of pharmacokinetics of dapoxetine in Europeans and Japanese showed higher values of Cmax and AUC, in the latter (by 10-20%) because of less body weight. A higher level of systemic exposure hardly causes a significant difference in the 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 pharmacokinetics (Cmax, AUC, Tmax) in healthy elderly men and men of younger age.The mean values of AUC of dapoxetine and the final half-life were higher, respectively, by 12% and 46% in older men compared with men of younger age.Impaired renal functionA single dose of 60 mg of dapoxetine did not reveal a relationship between creatinine clearance and Cmax or AUC of dapoxetine in patients with mild (creatinine clearance 50-80 ml / ml), moderately expressed (creatinine clearance from 30 to <50 ml / min) and heavy ( clearance of creatinine <30 ml / min) impaired renal function.AUC of dapoxetine in patients with severe renal dysfunction was approximately 2 times higher than in patients with normal renal function. Data on the use of the drug in patients with severe renal impairment are limited. In patients in need of hemodialysis, the pharmacokinetics of dapoxetine have not been studied.Impaired liver functionIn patients with a weak violation of liver function, the pharmacokinetics of dapoxetine and desmethyldapoxetine did not change. In patients with impaired liver function of moderate severity (Child-Pugh class B), Cmax and AUC of unbound dapoxetine are increased by 55% and 120%, respectively. The C max of the unbound active fraction of dapoxetine was unchanged, and the AUC was increased 2-fold.In patients with severe impairment of liver function, Cmax of unbound dapoxetine was unchanged, and the AUC of unbound dapoxetine was increased more than 3-fold. The AUC of the active fraction was also increased several fold.CYP2D6 polymorphismThe concentration of dapoxetine in the blood plasma after a single dose of Primaxetin® at a dose of 60 mg in patients with low CYP2D6 activity was higher than in patients with high activity of CYP2D6 (Cmax approximately 31%, AUC approximately 36%).Likewise, Cmax of desmethyldapoxetine in patients with low CYP2D6 activity was increased by 98%, and AUC by 161%. The average final half-life of dapoxetine was increased by 2.4 hours in patients with low activity of CYP2D6 isofermite, but compared to patients with high activity of the isoenzyme CYP2D6. The cmax of the active fraction of dapoxetine is increased by -46%, and the AUC by -90%. This increase may be accompanied by an increased frequency and severity of dose-related adverse events. The safety of using Primaxetin® in patients with low activity of CYP2D6 can cause doubts with simultaneous administration of other drugs that can inhibit the metabolism of dapoxetine. in particular, active and moderately active inhibitors of CYP3A4.It is expected that in patients with ultra-high activity of CYP2D6 the concentrations of dapoxetine and desmethyldapoxetine in blood plasma will be reduced. Indications:The drug Primaxetin® is designed to treat premature ejaculation in men aged 18 to 64 years. Contraindications:- Hypersensitivity to dapoxetine hydrochloride or any other component of the drug.- Severe heart disease (eg, grade II-IV heart failure by NYHA.cardiac conduction abnormalities (2-3-degree atrioventricular conduction block or sinus weakness syndrome) in the absence of a permanent pacemaker, severe ischemic heart disease, or valvular disease).- Simultaneous administration of monoamine oxidase inhibitors (MAO-I) and admission within 14 days after discontinuation of their use. Similarly, MAO-I can not be taken within 7 days after discontinuation of Primaxetin®.- Simultaneous reception of thioridazine and within 14 days after discontinuation of its use. Similarly, thioridazine Do not take within 7 days after discontinuation of Primaxetine.- Simultaneous reception of serotonin reuptake inhibitors (selective serotonin reuptake inhibitors-SSRIs), serotonin and noradrenaline reuptake inhibitors and tricyclic antidepressants) and other drugs with serotonergic action (for example, L-tryptophan, triptans, tramadol. linezolid, lithium, preparations of St. John's wort (Hypericum perforatum) and within 14 days after discontinuation of these medications. Likewise, these drugs can not be taken within 7 days after discontinuation of Primaxetine.- Simultaneous administration with active inhibitors of CYP3A4, for example, ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, atazanavir, etc.- Moderate and severe violations of the liver.- Severe renal dysfunction.- Children and teenagers under the age of 18.- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.If there is a history of established or suspected orthostatic hypotension, and a history of mania / hypomania or bipolar disorder, treatment with Primaxetin® should be avoided. Carefully:- mild or moderately severe renal dysfunction;- simultaneous use with potent inhibitors of the isoenzyme CYP2D6 and moderate inhibitors of CYP3A4 in patients with genotypically low activity of the isoenzyme CYP2D6 and patients with high isozyme activity CYP2D6 (in combination with moderate inhibitors of the isoenzyme CYP3A4);- simultaneous use with drugs that affect platelet aggregation and with anticoagulants due to the risk of bleeding. Pregnancy and lactation:Primaxetin® is not suitable for use in women.PregnancyBased on the limited amount of data obtained in clinical studies, there is no reason to assume that taking dapoxetine by a man can affect a partner's pregnancy. Well-controlled studies of dapoxetine in pregnant women have not been conducted.Breastfeeding periodIt is not known whether dapoxetine and its metabolites with breast milk. Dosing and Administration:For oral administration. The tablet should be swallowed whole, washed down with at least one full glass of water. The drug Primaxetine ® can be taken regardless of food intake.Adult men from 18 to 64 years oldThe recommended initial dose for all men is 30 mg; this dose is taken 1-3 hours before the alleged sexual intercourse. With insufficient effect and good tolerability of 30 mg dose, it can be increased to 60 mg. The maximum recommended dose frequency is 1 time per 24 hours.The doctor who prescribes Primaxetine® for the treatment of premature ejaculation should assess the risk and benefit of using the drug after the first 4 weeks of treatment or aftertaking 6 doses and should determine the risk-benefit ratio for deciding whether to continue treatment with Primaxetin®.Patients with impaired renal functionFor patients with mild or moderate renal impairment, dose adjustment is not required, but caution is advisable. Primaxetin® is not recommended for patients with severe renal dysfunction.Patients with impaired hepatic functionFor patients with a weak violation of liver function, dose adjustment is not required. The drug Primaxetin® is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B and C).Patients with low CYP2D6 activity, concurrent administration with active inhibitors of CYP2D6.Caution should be exercised when increasing the dose of Primaxetin® to 60 mg in individuals with low CYP2D6 activity or in patients concomitantly taking Primaxetine® taking active CYP2D6 inhibitors.Patients receiving active or moderately active inhibitors of CYP3A4 Simultaneous reception of active inhibitors of CYP3A4 is contraindicated.When taking Primaxetin® with moderately active inhibitors of CYP3A4, the dose should be reduced to 30 mg. Side effects:In clinical trials, the following side effects were observed, which were observed frequently and were dose-dependent: nausea (11.0% and 22.2% with 30 mg and 60 mg 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 (2.0% and 4.1%). The most frequent phenomena requiring withdrawal of treatment were nausea (2.2% of patients) and dizziness (1.2%).Unwanted adverse reactions observed in clinical trials are listed below:Mental disorders:Often: anxiety, agitation, anxiety, unusual dreams, decreased libido. Infrequently: depression, depressed mood, euphoria, mood changes, nervousness, indifference, apathy, confusion, disorientation, pathological thinking, somatosensory amplification, sleep disturbances, initial insomnia, intrasomnic disorder, nightmares, bruxism, loss of libido, anograzia. Disorders from the central nervous system:Very often: dizziness, headache.Often: drowsiness, impaired concentration, tremor, paresthesia.Infrequent: fainting, including vasovagal syncope, postural dizziness, akathisia, taste distortion, hypersomnia, lethargy, sedative state, depression of consciousness.Rarely: dizziness with physical exertion, sudden falling asleep.Disturbances on the part of the organ of sight: Often: blurred vision.Infrequently: mydriasis, pain in the eye area, impaired vision.Hearing disorders and labyrinthine disorders:Often: ringing in the ears.Infrequently: vertigo.Disorders from the cardiovascular system:Often: "hot flashes" of blood.Infrequent: cessation of sinus node activity, sinus bradycardia, tachycardia, lowering of arterial pressure, systolic hypertension.Rarely: "hot flashes" of heat.Disturbances from the respiratory system:Often: nasal congestion, yawning.Disorders from the gastrointestinal tract:Often: diarrhea, vomiting, constipation, abdominal pain, dyspepsia, flatulence, stomach discomfort, bloating, dry mouth.Disturbances from the skin and subcutaneous tissues:Often: hyperhidrosis.Infrequent: itching, cold sweat.Disorders from the reproductive system:Often: erectile dysfunction.Infrequently: absence of ejaculation, violation of orgasm, including anorgasmia in men, paresthesia of male genital organs.General state:Often: weakness, irritability.Infrequently: asthenia, a feeling of heat, a sense of anxiety, a feeling of discomfort, a feeling of intoxication.Changes in laboratory indicators:Often: increased blood pressure.Infrequent: increased heart rate, increased diastolic blood pressure, increased orthostatic blood pressure.Description of individual side effectsFainting with loss of consciousness, with bradycardia or the arrest of the sinus node, was observed in patients with Holter monitoring and was recorded in clinical studies. These adverse events are regarded as associated with the use of the drug. Most cases were observed within the first 3 hours after taking the drug, after taking the first dose or associated with medical procedures (blood sampling, changes in body position, measurement of blood pressure). Prodromal symptoms often preceded syncope.The incidence of syncope and prodromal symptoms was dose dependent, which was demonstrated in patients receiving higher doses of the drug.Effects of drug cancellationWith the sudden reversal of long-term selective serotonin reuptake inhibitors for the treatment of chronic depressive disorders, the following symptoms were noted: dysphoric status, irritability, agitation, dizziness, sensory disturbances (eg, paresthesia), anxiety, confusion, headache, lethargy, emotional lability, insomnia and hypomania. The results of the safety study showed a higher incidence of withdrawal symptoms in the form of insomnia and mild to moderate dizziness after discontinuation of the drug after 62 days of use. Overdose:SymptomsIn clinical studies, cases of overdose are not described.The administration of Primaxetine® in a dose of 240 mg (2 doses of 120 mg at 3-hour intervals) did not cause unforeseen adverse events. In general, symptoms of SSRI overdose include serotonergic reactions, including drowsiness, gastrointestinal disorders (nausea, vomiting), tachycardia, tremor, agitation and dizziness.TreatmentWhen an overdose should be, if necessary, to conduct a standard maintenance therapy. Due to the significant binding of the drug to blood plasma proteins and a large volume of distribution of dapoxetine hydrochloride, forced diuresis, dialysis, hemoperfusion and blood transfusion are unlikely to be effective. The specific antidote is unknown. Interaction:Interaction with monoamine oxidase inhibitorsSerious and sometimes fatal reactions, including hyperthermia, stiffness, myoclonus, instability of the autonomic system with possible rapid fluctuations in vital signs, as well as changes in mental state, including severe hypertension, are described in patients receiving SSRI and monoamine oxidase inhibitor (MAO-I) simultaneously including strong excitation, progressing to delirium and coma. These reactions were also observed in patients who recently stopped taking SSRIs and started treatment with Mao-I. In some cases, the symptoms resembled a malignant neuroleptic syndrome. Data on the combined use of SSRIs and MAO-I in animals suggest that these drugs can synergistically increase blood pressure and cause behavioral arousal.Therefore, the drug Primaxetin ® should not be taken simultaneously with MAO-I and within 14 days after discontinuation of their administration. Similarly, MAO-I can not be taken within 7 days after discontinuation of Primaxetin®.Interaction with thioridazineThioridazine prolongs the QTc interval, which is accompanied by ventricular arrhythmia. Preparations such as Primaxetin®, which inhibit the enzyme CYP2D6, seem to inhibit the metabolism of thioridazine. It is expected that the resulting increase in the level of thioridazine will increase the elongation of the QTc interval. Primaxetin® should not be taken concomitantly with thioridazine and within 14 days after discontinuation of its administration. Similarly, thioridazine Do not take within 7 days after discontinuation of Primaxetine.Drugs that have a serotonergic effectAs in the case of SSRIs, the administration of Primaxetin® concomitantly with serotonergic drugs (including MAO-I, L-tryptophan, triptans, tramadol, linezolid, SSRIs, serotonin and norepinephrine seizure inhibitors, lithium and St. John's wort preparations (Hypericum perforatum) can increase the incidence of serotonergic side effects.Primaxetin® should not be taken concomitantly with other SSRIs, MAO-I and other serotonergic drugs and within 14 days after discontinuation of these medications. Likewise, these drugs can not be taken within 7 days after discontinuation of Primaxetine.Drugs acting on the central nervous systemThe administration of Primaxetine® concomitantly with drugs acting on the central nervous system in patients with premature ejaculation has not been studied. It is recommended to be cautious when it is necessary to take these drugs at the same time.The effect of other drugs on dapoxetine hydrochlorideStudies using microsomes of the liver, kidney and intestines in vitro have shown that dapoxetine is metabolized predominantly by CYP2D6. CYP3A4 and flavin-containing monooxygenase 1 (FM01). Therefore, inhibitors of these enzymes can reduce the clearance of dapoxetine.Inhibitors of CYP3A4 Active inhibitors of CYP3A4Taking ketoconazole 200 mg twice daily for 7 days increased Cmax and AUC of dapoxetine (60 mg once) by 35% and 99%, respectively. Taking into account the fraction of unbound dapoxetine and desmethyldapoxetine,The C max of the active fraction (the amount of unbound dapoxetine and desmethyldapoxetine) in the presence of active inhibitors of CYP3A4 may increase by approximately 25%, and the AUC can double. This increase in Cmax and AUC of the active fraction can be significantly more pronounced in the subpopulation of patients not having a functionally active CYP2D6 enzyme, as well as simultaneous administration of active inhibitors of CYP2D6,Primaxetin® should not be taken concomitantly with active inhibitors of CYP3A4, for example, ketoconazole, intraconazole, ritonavir, saquinavir, telithromycin, isfazodone, nelfinavir and atazanavir.Moderately active inhibitors of CYP3A4Simultaneous administration of moderately active inhibitors of CYP3A4, for example erythromycin, clarithromycia, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil or diltiazem, can significantly increase the systemic exposure to dapoxetine and desmethyldapoxetine, especially in patients with low CYP2D6 activity. The maximum dose of Primaxetin® taken concomitantly with these drugs should be limited to 30 mg and taken with caution.Active inhibitors of CYP2D6Taking fluoxetine at a dose of 60 mg / day for 7 days increased Cmax and AUC of dapoxetine (60 mg once) by 50% and 88%, respectively. Taking into account the fraction of unbound dapoxetine and desmethyldapoxetine, the Cmax of the active fraction (the amount of unbound dapoxetine and desmethyldapoxetine) in the presence of active inhibitors of CYP2D6 can increase by approximately 50%, and the AUC can be doubled. This increase in Cmax and AUC of the active fraction is close to that expected in patients with low CYP2D6 activity and may increase the frequency and severity of dose-dependent adverse reactions. Therefore, caution should be exercised when increasing the dose of Primaxetin® to 60 mg in patients receiving active inhibitors of CYP2D6, and in patients with low activity of CYP2D6.Interaction with drugs metabolized by isoenzymes CYP1A and CYP2B6Based on the comparative data of Cmax dapoxetine when taking a dose of 60 mg and the concentration of dapoxetine at 50% inhibition (ICso) of the CYP1A2 isoenzyme in vitro, it was concluded that the effect of dapoxetine on the concentration of concurrently administered drugs metabolized by this isoenzyme is not expected. The effect of dapoxetine on the isoenzyme CYP2B6 has not been studied.Inhibitors of PDE5The pharmacokinetics of dapoxetine, taken at a dose of 60 mg concomitantly with tadalafil (20 mg) or sildenafil (100 mg), was studied. Tadalafil did not affect the pharmacokinetics of dapoxetine. Sildenafil slightly increased the AUC and Cmax of dapoxetine (by 22% and 4%, respectively), which is considered clinically insignificant. Primaxetin® should be given with caution to patients taking PDE5 inhibitors, because of the possibly reduced tolerance of these patients to orthostatic hypotension.Effect of dapoxetine hydrochloride on concurrently taken drugsTamsulosinSingle and multiple administration of the drug Primaxetin® in doses of 30 mg and 60 mg in patients receiving daily tamsulosin, did not lead to a change in the pharmacokinetics of the latter. There was also no change in the frequency of orthostatic hypotension, which was the same with tamsulosin alone and in a combination of tamsulosin with Primaxetin® 30 mg or 60 mg. Primaxetin® should be given with caution to patients taking alpha-blockers, because of the possibly reduced tolerance of these patients to orthostatic hypotension. Drugs metabolized by CYP2D6Multiple administration of Primaxetine® (60 mg / day for 6 days) increased Cmax and AUC of desipramine (50 mg once) by 11% and 19% respectively, compared with the use of desipramine alone. Dapoxetine can similarly increase the concentration in the blood plasma and other drugs metabolized by CYP2D6. The clinical significance of this is likely to be small.Drugs metabolized by CYP3AMultiple administration of Primaxetine® (60 mg / day for 6 days) reduced the AUC of midazolam (8 mg once) by approximately 20% (range from -60% to + 18%). The clinical significance of this phenomenon in most patients is likely to be small. However, an increase in CYP3A activity may be of clinical importance in some patients concurrently taking drugs metabolized primarily by CYP3A and having a narrow therapeutic window.Drugs metabolized by CYP2C19Multiple administration of Primaxetin® (60 mg / day for 6 days) did not affect the pharmacokinetics of omeprazole (40 mg once). Dapoxetine hardly affects the pharmacokinetics of other CYP2C19 substrates.Drugs metabolized by CYP2C9Multiple administration of Primaxetine® (60 mg / day for 6 days) did not affect the pharmacokinetics and pharmacodynamics of glyburide (5 mg once). Dapoxetine hardly affects the pharmacokinetics of other CYP2C9 substrates.Inhibitors of PDE5By the results of the study dapoxetine (60 mg) did not affect the pharmacokinetics of tadalafil (20 mg) and sildenafil (100 mg).WarfarinData on the effects of long-term taking of warfarin concomitantly with the preparation of Primaxetine® are not available. It is recommended to be cautious when prescribing Primaxetine® to patients who take long-term warfarin. In the study of pharmacokinetics, repeated administration of dapoxetine (60 mg / day for 6 days) did not affect the pharmacokinetics and pharmacodynamics (PV and INR) of warfarin (25 mg once). EthanolA single dose of ethanol (0.5 g / kg, or approximately 2 doses) did not affect the pharmacokinetics of dapoxetine (60 mg once) and vice versa. Simultaneous administration of the drug Primaxetin® and ethanol increased drowsiness and significantly reduced the level of wakefulness in the patient's assessment. Admission of only ethanol and only the preparation of Primaxetin® did not significantly change the cognitive functions (reaction rate in the digest recognition test and in the symbol replacement test) compared with placebo, but the combination of ethanol with Primaxetin® statistically significantly altered these values compared to ethanol alone .Simultaneous administration of ethanol and the drug Primaxetin® increases the frequency and severity of such undesirable reactions as dizziness, drowsiness, slowing down of reflexes, changing judgments. Combination with alcohol Primaksetin® preparation 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 drinking alcohol during the period of treatment with the drug Primaxetin®. Special instructions:Are commonThe drug Primaxetin® is only for men with premature ejaculation. The safety of the drug in men without premature ejaculation is not established, there is no data on ejaculation delay.Admission with drugsPatients should be advised not to take Primaxetin® along with narcotic drugs. Simultaneous reception Primaksetin® preparation with preparations having serotonergic activity, e.g., ketamine, methylenedioxymethamphetamine (MDMA) and lysergic acid diethylamide (LSD) can lead to potentially severe reactions, including but not limited to, arrhythmia, hyperthermia and serotonin syndrome.Taking Primaxetin® along with sedatives such as opiates or benzodiazepines may increase drowsiness and dizziness.EthanolThe combination of Primaxetin® with alcohol can enhance the effect of the drug on the central nervous system and neuro-cardiogenic side effects of alcohol, for example, syncope, which increases the risk of accidental injury. Therefore, patients should be advised to refrain from drinking alcohol during the period of taking Primaxetin®. FaintingThe frequency of syncope in clinical studies of the drug Primaxetin® depended on the patient category and ranged from 0.06% (for a dose of 30 mg) to 0.23% (for a dose of 60 mg) to 0.64% (for both doses together) in a study involving healthy volunteers.Patients treated with Primaxetine® received more prodromal symptoms than patients who received placebo, including nausea, dizziness / lightheadedness, and sweating. With a dose of Primaxetin® 30 mg, the incidence of nausea was 11.0%, the incidence of dizziness was 5.8%, and the hyperhidrosis 0.8%. At a dose of Primaxetin® 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 indicated by higher rates in patients receiving higher doses than the maximum recommended daily dose of 60 mg. The cases of syncope observed in clinical trials were regarded as having a vaso-vagal nature. Most of these cases occurred within the first 3 hours after the first dose, or were associated with conducting research procedures in a clinical setting (for example, taking a blood sample, abruptly rising, measuring blood pressure). Possible prodromal symptoms, such as nausea, dizziness, lightheadedness, palpitations, asthenia, confusion and sweating, were also usually observed in the first 3 hours after taking the drug and often preceded fainting. Patients should be informed that during the treatment with the drug Primaxetin® at any time, a syncope with or without prodromal symptoms may develop. The physician should inform the patient of the importance of sufficient water stress and the recognition of prodromal signs and symptoms to reduce the risk of serious injury if dropped due to loss of consciousness.When there are possible prodromal symptoms, the patient should immediately lie down so that the head is below the trunk, or sit down, head down between the knees, and must remain in this position until the symptoms disappear. If there is fainting or other effects from the central nervous system, the patient should be warned to avoid potentially traumatic situations, including driving and managing dangerous machinery.The combination of Primaxetin® with alcohol may increase neurocardiogenic side effects, including syncope, which increases the risk of accidental trauma; therefore, patients should be advised to refrain from drinking alcohol during the period of treatment with Primaxetin®Patients with a risk of cardiovascular diseaseIn clinical studies of the drug did not participate patients with cardiovascular diseases. In patients with organic diseases of the heart and blood vessels (for example, obstruction of the discharge of blood from the heart, damage to the valve apparatus, stenosis of the carotid artery, coronary artery atherosclerosis), the risk of unwanted cardiovascular consequences of syncope of cardiac and other origin is increased.However, at present there is insufficient data to determine whether this risk extends to vaso-vagal syncope in patients with cardiovascular disease. Orthostatic hypotensionIn clinical trials, cases of orthostatic hypotension have been described. The doctor should inform the patient in advance that if there are possible prodromal symptoms, for example, a feeling of lightness in the head immediately after getting up, you should immediately lie down so that your head is below your torso, or sit down with your head between your knees, and stay 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 Primaxetin® should be administered with caution to patients taking vasodilator drugs (eg, alpha-blockers, nitrates, PDE5 inhibitors), because of the possible reduced tolerance of such patients to the orthostatic action of the drug. Moderately active inhibitors of CYP3A4.When taking Primaxetin® concomitantly with moderately active inhibitors of CYP3A4 (erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem) the dose should be reduced to 30 mg, caution should be exercised.Active inhibitors of CYP2D6It is advisable to use caution when increasing the dose of Primaxetin® to 60 mg in patients receiving active inhibitors of CYP2D6 and in patients with low CYP2D6 activity, as this may increase the systemic exposure to the drug with a corresponding increase in the frequency and severity of dose-related adverse events.Suicide / suicidal thoughtsIn short-term studies, antidepressants, including SSRIs, increased the risk of suicide and suicidal ideation in children and adolescents with generalized depression and other psychiatric disorders compared with placebo. In adults over 24 years of this effect is not found. In clinical studies of the drug Primaxetin ® for the treatment of premature ejaculation of clear data on the relationship of suicidal thoughts with treatment has not been received.ManiaPrimaxetin® should not be taken in patients with a history of mania / hypomania or bipolar disorder, when symptoms of these diseases appear, the drug should be discontinued.ConvulsionsBecause of the ability of SSRIs to reduce the convulsive threshold, the administration of Primaxetine® to patients with unstable epilepsy should be avoided, and the drug should be withdrawn if seizures occur. Patients with controlled epilepsy require careful monitoring.Admission in children and adolescents under the age of 18Primaxetine® should not be taken in patients younger than 18 years of age.Concomitant depression and mental disordersIf the patient has signs and symptoms of depression prior to the use of Primaxetin®, a check should be performed to exclude the presence of undiagnosed depressive disorder. Primaxetin® should not be taken concomitantly with antidepressants, including SSRIs and serotonin and noradrenaline reuptake inhibitors. It is not recommended to stop treatment of depression or anxiety for the initiation of treatment with the drug Primaxetin®. The drug Primaxetin® is not intended for the treatment of mental disorders (eg, schizophrenia or depression), it should not be taken by men with these diseases, since the symptoms of depression can not be ruled out.Immediately advise your doctor of any troublesome thoughts or feelings, and when signs and symptoms of depression appear during treatment, Primaxetine® should be discontinued.BleedingWhen using SSRIs, cases of bleeding are described. Caution is advised when taking Primaxetin® concomitantly with drugs that affect platelet function (for example, atypical antipsychotics, phenothiazines, acetylsalicylic acid, non-steroidal anti-inflammatory drugs (NSAIDs), anticoagulants), as well as in patients with bleeding or history of clotting.Impaired renal functionPrimaxetin® is not recommended for patients with severe renal dysfunction, patients with moderate to mild renal impairment should be cautious.The withdrawal syndromeThere is evidence that the abrupt withdrawal of SSRIs, long used for the treatment of chronic depressive disorders, leads to the following symptoms: decreased mood, irritability, agitation, dizziness, sensitivity disorders (eg, paresthesia in the form of an electric shock),anxiety, confusion, headache, lethargy, emotional instability, insomnia, hypomania.A clinical study conducted to assess the effect of dapoxetine withdrawal after 62 days of 60 mg doses (daily or on demand) in patients with premature ejaculation showed no signs of withdrawal syndrome. After transferring patients to placebo after daily dapoxetine administration, only minor withdrawal symptoms were found in the form of mild or moderate insomnia and dizziness. Similar results were obtained in another clinical trial with double-blind control with a weekly evaluation period of withdrawal effects after 24 weeks of drug use at a dose of 30 mg or 60 mg as needed. Effect on the ability to drive transp. cf. and fur:When taking dapoxetine, cases of dizziness, attention disturbances, fainting, blurred vision, drowsiness are described. The patient should be warned to avoid situations in which injuries can occur, including driving and managing dangerous machinery. Form release / dosage:The film-coated tablets are 30 mg and 60 mg. Packaging:By 3, 6 or 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.For 1 or 2 contour packs, together with the instructions for use are placed in a pack of cardboard. Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children. Shelf life:3 years. Do not use after the expiry date printed on the package. Terms of leave from pharmacies:On prescription Registration number:LP-003857 Date of registration:27.09.2016 Expiration Date:27.09.2021 The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia Manufacturer: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia Information update date: & nbsp2016-10-09 Illustrated instructions × Illustrated instructions Instructions