Inside, the tablet should be swallowed whole with at least 1 full glass of water. Primaxetin® can be taken with or without food.

Adult men from 18 to 64 years old. The recommended starting dose for all men is 30 mg; this dose is taken 1–3 hours before the expected sexual intercourse. If the effect is insufficient and the dose of 30 mg is well tolerated, it can be increased to 60 mg. The maximum recommended dose frequency is 1 time per 24 hours.

The doctor who prescribes the drug Primaxetin® for the treatment of premature ejaculation should assess the risks and benefits of using the drug after the first 4 weeks of treatment or after taking 6 doses and determine the risk-benefit ratio for deciding on the advisability of further treatment with Primaxetin®.

Special patient groups

Impaired renal function. For patients with mild to moderate renal impairment, dose adjustment is not required, but caution is advised. The drug Primaxetin® is not recommended for patients with severe renal impairment.

Liver dysfunction. No dose adjustment is required for patients with mild liver dysfunction. Primaxetin® is contraindicated in patients with moderate and severe liver dysfunction (classes B and C according to the Child-Pugh classification).

Low activity of CYP2D6, simultaneous administration with active inhibitors of CYP2D6. Caution should be exercised when increasing the dose of Primaxetin® to 60 mg in persons with low CYP2D6 activity or in patients taking active CYP2D6 inhibitors simultaneously with Primaxetin®.

Taking active or moderately active CYP3A4 inhibitors. Concomitant use of active CYP3A4 inhibitors is contraindicated. While taking the drug Primaxetin® with moderately active inhibitors of CYP3A4, the dose of the drug should be reduced to 30 mg.

Hypersensitivity to dapoxetine hydrochloride or any other component of the drug;

severe heart disease, incl. heart failure of NYHA class II – IV, cardiac conduction disorders (blockade of atrioventricular conduction of grade 2-3 or weak sinus syndrome) in the absence of a permanent pacemaker, severe ischemic heart disease or damage to the valve apparatus;

simultaneous administration of MAO inhibitors and taking within 14 days after the termination of their use (similarly, MAO inhibitors should not be taken within 7 days after stopping the drug Primaxetin®);

simultaneous administration of thioridazine and within 14 days after the termination of its use (similarly, thioridazine should not be taken within 7 days after discontinuation of the drug Primaxetin®);

concomitant use of SSRIs, SNRIs and tricyclic antidepressants and other drugs with serotonergic action (including L-tryptophan, triptans, tramadol, linezolid, lithium, St. John's wort (Hypericum perforatum), and within 14 days after stopping these drugs (similarly, these drugs should not be taken within 7 days after discontinuation of Primaxetin®);

concomitant use with active CYP3A4 inhibitors (including ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, atazanavir);

moderate and severe liver dysfunction;

severe renal impairment;

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

a history of established or suspected orthostatic hypotension;

a history of mania / hypomania or bipolar disorder;

age up to 18 years.

With care: mild or moderate renal impairment; 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 activity of the isoenzyme 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.

  Application during pregnancy and lactation:

Primaxetin® is not intended for use in women.

Based on the limited amount of data obtained from clinical studies, there is no reason to assume that dapoxetine intake by a man may affect a partner's pregnancy. There are no well-controlled studies of the use of dapoxetine in pregnant women.

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

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

The undesirable side effects 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, anorgasmia.

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

From the side of the organ of vision: often - blurred vision; infrequently - mydriasis, pain in the eye area, visual impairment.

From the side of the organ of hearing and labyrinth disorders: often - ringing in the ears; infrequently - vertigo.

From the CCC: often - hot flushes; infrequently - cessation of sinus node activity, sinus bradycardia, tachycardia, lowering blood pressure, systolic hypertension; rarely - hot flashes.

On the part of the respiratory system: often - nasal congestion, yawning.

From the gastrointestinal tract: often - diarrhea, vomiting, constipation, abdominal pain, dyspepsia, flatulence, stomach discomfort, bloating, dry mouth.

From the side of the skin and subcutaneous tissues: often - hyperhidrosis; infrequently - itching, cold sweat.

From the reproductive system: often - erectile dysfunction; infrequently - lack of ejaculation, violation of orgasm, incl. anorgasmia in men, paresthesia of the genitals of men.

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

Changes in laboratory parameters: often - increased blood pressure; infrequently - an increase in heart rate, an increase in blood pressure, an increase in blood pressure.

Description of selected side effects

Syncope with loss of consciousness, bradycardia, or sinus node arrest have been observed in patients under Holter monitoring and have been reported in clinical trials. These adverse events were regarded as related to the use of the drug. Most cases were observed within the first 3 hours after taking the drug, taking the first dose, or associated with medical procedures (blood sampling, changes in body position, blood pressure measurement). Prodromal symptoms often preceded syncope.

The incidence of syncope and prodromal symptoms was dose dependent, as demonstrated in patients receiving higher doses of the drug.

Effects of drug withdrawal

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

MAO inhibitors

In patients who received both SSRIs and an MAO inhibitor, serious, sometimes fatal reactions have been described, incl. hyperthermia, rigidity, myoclonus, instability of the autonomic system with possible rapid fluctuations in vital signs, as well as changes in mental state, incl. great excitement, progressing to delirium and coma. These reactions have also been observed in patients who recently stopped taking SSRIs and started treatment with MAO inhibitors. In some cases, the symptoms resembled 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 induce behavioral arousal. Therefore, the drug Primaxetin® should not be taken simultaneously with MAO inhibitors and within 14 days after stopping them. Similarly, MAO inhibitors should not be taken within 7 days after discontinuation of Primaxetin®.

Thioridazine

Thioridazine prolongs the QTc interval, which is accompanied by ventricular arrhythmia. Drugs like Primaxetin®, which inhibit the CYP2D6 enzyme, seem to inhibit the metabolism of thioridazine. The increase in thioridazine level caused by this is expected to increase the prolongation of the QTc interval. The drug Primaxetin® should not be taken simultaneously with thioridazine and within 14 days after stopping it. Similarly, thioridazine should not be taken within 7 days after discontinuation of Primaxetin®.

Drugs with serotonergic action

As in the case of SSRIs, taking Primaxetin® simultaneously with serotonergic drugs (including MAO inhibitors, L-tryptophan, triptans, tramadol, linezolid, SSRIs, SNRIs, lithium and St. John's wort (Hypericum perforatum) can increase the frequency of serotoninergic The drug Primaxetin® should not be taken simultaneously with other SSRIs, MAO inhibitors and other serotonergic drugs and within 14 days after stopping these drugs.Likewise, these drugs should not be taken within 7 days after stopping the drug Primaxetin®.

Drugs acting on the CHC

Taking Primaxetin® simultaneously with drugs acting on the central nervous system has not been studied in patients with premature ejaculation. It is advised to exercise caution when taking these drugs at the same time

Effect of other drugs on dapoxetine

In vitro studies using human liver, kidney and intestinal microsomes have shown that dapoxetine is metabolized predominantly by CYP2D6, CYP3A4 and FMO1. Therefore, inhibitors of these enzymes can reduce the clearance of dapoxetine.

CYP3A4 inhibitors

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

The drug Primaxetin® should not be taken simultaneously with active inhibitors of CYP3A4, incl. ketoconazole, intraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, and atazanavir.

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

Active inhibitors of CYP2D6

Taking fluoxetine at a dose of 60 mg / day for 7 days increased the Cmax and AUC 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 sum of unbound dapoxetine and desmethyldapoxetine) in the presence of active CYP2D6 inhibitors can increase by about 50%, and the AUC can double. This increase in Cmax and AUC of the active fraction is close to that expected in patients with low CYP2D6 activity and can lead to an increase in the frequency and severity of dose-dependent adverse reactions. Therefore, it is recommended to exercise caution when increasing the dose of Primaxetin® to 60 mg in patients receiving active CYP2D6 inhibitors and in patients with low CYP2D6 activity.

Drugs metabolized by isoenzymes CYP1A and CYP2B6

Based on the comparative data of Cmax of dapoxetine at a dose of 60 mg and the IC50 of the isoenzyme CYP1A2 in vitro, it was concluded that the effect of dapoxetine on the concentration of simultaneously prescribed drugs metabolized by this isoenzyme is not expected. 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 AUC and Cmax of dapoxetine (by 22 and 4%, respectively), which is considered clinically insignificant. The drug Primaxetin® should be prescribed with caution to patients taking PDE-5 inhibitors, because of the possible reduced tolerance of these patients to orthostatic hypotension.

 

Effect of dapoxetine on concomitant medications

 

Tamsulosin. Single and multiple administration of the drug Primaxetin® in doses of 30 and 60 mg by patients receiving daily tamsulosin did not change the pharmacokinetics of the latter. At the same time, the frequency of orthostatic hypotension did not change either, which was the same when taking tamsulosin alone and the combination of tamsulosin with Primaxetin® 30 or 60 mg. The drug Primaxetin® should be prescribed with caution to patients taking alpha-blockers, because of the possible reduced tolerance of these patients to orthostatic hypotension.

Drugs metabolized by CYP2D6

 

Repeated administration of the drug Primaxetin® (60 mg / day for 6 days) increased the Cmax and AUC of desipramine (50 mg once) by 11 and 19%, respectively, compared to taking only desipramine. Dapoxetine may similarly increase plasma concentrations of other drugs metabolized by CYP2D6. The clinical significance of this is likely to be small.

 

Drugs metabolized by CYP3A

 

Repeated administration of Primaxetin® (60 mg / day for 6 days) reduced the AUC of midazolam (8 mg once) by about 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 significance in some patients who are concurrently taking drugs metabolized primarily by CYP3A and have a narrow therapeutic window.

Drugs metabolized by CYP2C19

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

Drugs metabolized by CYP2C9

Multiple administration of Primaxetin® (60 mg / day for 6 days) did not affect the pharmacokinetics and pharmacodynamics of glyburide (5 mg once). Dapoxetine is unlikely to interfere with the pharmacokinetics of other CYP2C9 substrates.

PDE-5 inhibitors

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

Warfarin

There are no data on the effects of long-term administration of warfarin simultaneously with Primaxetin®. It is recommended to exercise caution when prescribing Primaxetin® to patients taking warfarin for a long time. In a pharmacokinetic study, repeated administration of dapoxetine (60 mg / day for 6 days) did not affect the pharmacokinetics and pharmacodynamics (PT and INR) of warfarin (25 mg once).

Ethanol

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 Primaxetin® and ethanol increased drowsiness and significantly reduced the level of wakefulness when evaluated by the patient. Taking only ethanol and only Primaxetin® did not significantly change the indicators of cognitive functions (reaction rate in the digit recognition test and the digit substitution test) compared with placebo, however, the combination of ethanol with Primaxetin® statistically significantly changed these indicators compared to ethanol alone.

The simultaneous intake of ethanol and the drug Primaxetin® increases the frequency and severity of such undesirable reactions as dizziness, drowsiness, slowing reflexes, changes in judgment. The combination of alcohol with Primaxetin® can also increase neurocardiogenic 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 Primaxetin®.

Symptoms: in clinical studies, cases of overdose have not been described. Taking Primaxetin® in a dose of up to 240 mg (2 doses of 120 mg with an interval of 3 hours) did not cause unforeseen adverse events. In general, symptoms of an SSRI overdose include serotonergic reactions, incl. drowsiness, gastrointestinal disturbances (nausea, vomiting), tachycardia, tremors, agitation and dizziness.

Treatment: if necessary, carry out standard supportive therapy. Due to the significant binding of the drug to blood plasma proteins and the large Vd of dapoxetine hydrochloride, forced diuresis, dialysis, hemoperfusion and blood transfusion are unlikely to be effective. The specific antidote is unknown.

General

Primaxetin® is intended only for men with premature ejaculation. The safety of using the drug in men without premature ejaculation has not been established, and there is no data on delayed ejaculation.

Reception together with drugs

Patients should be advised not to take Primaxetin® together with narcotic drugs. Simultaneous administration of the drug Primaxetin® with substances with serotonergic activity, incl. ketamine, methylenedioxymethamphetamine (MDMA) and lysergic acid diethylamide (LSD) can lead to potentially serious reactions including, but not limited to, arrhythmia, hyperthermia, and serotonin syndrome. Taking the drug Primaxetin® together with sedatives, incl. opiates or benzodiazepines may worsen drowsiness and dizziness.

Ethanol

The combination of the drug Primaxetin® with alcohol can enhance the effect of the latter on the central nervous system and the neurocardiogenic side effects of alcohol, incl. fainting, which increases the risk of accidental injury. Therefore, patients should be advised to refrain from drinking alcohol while taking Primaxetin®.

Fainting

The frequency of syncope in clinical trials of 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 with healthy volunteers.

In patients who received the drug Primaxetin®, compared with patients who received placebo, prodromal symptoms were more often observed, incl. nausea, dizziness / lightheadedness and sweating. At a dose of Primaxetin® 30 mg, the frequency of nausea was 11%, the frequency of dizziness was 5.8%, and hyperhidrosis was 0.8%. At a dose of the drug Primaxetin® 60 mg, these figures were 21.2; 11.7 and 1.5%, respectively. The incidence of syncope and possible prodromal symptoms was dose-dependent, as evidenced by the higher rates in patients receiving higher doses than the maximum recommended daily dose of 60 mg. Cases of syncope observed in clinical studies were regarded as having a vasovagal nature. Most of these cases occurred within the first 3 hours after taking the first dose, or were associated with conducting research procedures in a clinical setting (including taking a blood sample, standing up suddenly, measuring blood pressure). Possible prodromal symptoms, incl. nausea, dizziness, a feeling of lightness in the head, palpitations, asthenia, confusion and sweating, were usually also observed in the first 3 hours after taking the drug and often preceded fainting. Patients should be informed that during the period of treatment with Primaxetin® at any time, fainting may develop with or without prodromal symptoms. The clinician should educate the patient about the importance of adequate water loading and recognition of prodromal signs and symptoms to reduce the risk of serious fall injury due to loss of consciousness. When possible prodromal symptoms appear, the patient should immediately lie down so that the head is below the torso, or sit with the head bowed between the knees, and should remain in this position until the symptoms disappear. If fainting or other effects from the central nervous system appear, the patient should be warned about the need to avoid potentially traumatic situations, including driving a car and operating dangerous machinery.

The combination of the drug Primaxetin® with alcohol intake can increase neurocardiogenic side effects, incl. fainting, which increases the risk of accidental injury; therefore, patients should be advised to refrain from drinking alcohol during the period of treatment with Primaxetin®.

Patients at risk of cardiovascular disease

Patients with cardiovascular diseases did not participate in clinical trials of the drug. In patients with organic diseases of the heart and blood vessels (including obstruction of the ejection of blood from the heart, damage to the valve apparatus, stenosis of the carotid artery, atherosclerosis of the coronary artery), the risk of undesirable cardiovascular consequences of syncope of cardiac and other origin is increased. However, there is currently insufficient data to determine whether this risk extends to vasovagal syncope in patients with cardiovascular disease.

Orthostatic hypotension

Cases of orthostatic hypotension have been described in clinical studies. The doctor should inform the patient in advance that if possible prodromal symptoms appear, incl. feeling of lightness in the head immediately after standing up, one should immediately lie down so that the head is lower than the body, or sit with the head bowed between the knees, and remain in this position until the symptoms disappear. In addition, the patient should be informed about the need to avoid getting up suddenly after prolonged lying or sitting. In addition, the drug Primaxetin® should be prescribed with caution to patients taking vasodilating drugs (including alpha-blockers, nitrates, PDE-5 inhibitors), because of the possible reduced tolerance of such patients to the orthostatic effect of the drug.

Moderately potent CYP3A4 inhibitors

When taking Primaxetin® concurrently with moderately active CYP3A4 inhibitors (erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem), the dose of the drug should be reduced to 30 mg, caution should be exercised.

Active inhibitors of CYP2D6

It is recommended to exercise caution when increasing the dose of Primaxetin® to 60 mg in patients receiving active CYP2D6 inhibitors and in patients with low CYP2D6 activity, since this may increase the level of systemic exposure to the drug with a corresponding increase in the frequency and severity of dose-dependent adverse events.

Suicide / suicidal thoughts

In 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 to placebo. No such effect was found in adults over 24 years of age. In clinical trials of the drug Primaxetin® for the treatment of premature ejaculation, clear data on the relationship of suicidal thoughts with treatment have not been obtained.

Mania

The drug Primaxetin® should not be taken by patients with a history of mania / hypomania or bipolar disorder; if symptoms of these diseases appear, the drug should be discontinued.

Convulsions

Due to the ability of SSRIs to reduce the seizure threshold, Primaxetin® should be avoided in patients with unstable epilepsy; if seizures occur, the drug should be discontinued. Patients with controlled epilepsy require close monitoring.

Admission for children and adolescents under 18 years of age

The drug Primaxetin® should not be taken by patients under 18 years of age.

Comorbid depression and mental health problems

If the patient has signs and symptoms of depression, prior to using the drug Primaxetin®, it is necessary to conduct an examination to exclude the presence of an undiagnosed depressive disorder. The drug Primaxetin® cannot be taken simultaneously with antidepressants, including SSRIs and SNRIs. It is not recommended to discontinue treatment for depression or anxiety in order to start treatment with Primaxetin®. The drug Primaxetin® is not intended for the treatment of mental disorders (including schizophrenia or depression), it should not be taken by men with these diseases, since this cannot exclude an increase in the symptoms of depression. You should immediately inform your doctor about any disturbing thoughts or sensations, and if signs and symptoms of depression appear during treatment, Primaxetin® should be discontinued.

Bleeding

Cases of bleeding have been reported with SSRIs. It is recommended to exercise caution when taking Primaxetin® simultaneously with drugs that affect platelet function (including atypical antipsychotics, phenothiazines, acetylsalicylic acid, NSAIDs, anticoagulants), as well as in patients with a history of bleeding or blood clotting disorders.

Impaired renal function

The drug Primaxetin® is not recommended for patients with severe renal impairment, patients with moderate and mild renal impairment should exercise caution.

Withdrawal syndrome

There is evidence that the abrupt withdrawal of SSRIs, which have been used for a long time to treat chronic depressive disorders, leads to the following symptoms: decreased mood, irritability, agitation, dizziness, impaired sensitivity (including paresthesia in the form of a feeling of electric shock), anxiety, confusion, headache, lethargy, emotional instability, insomnia, hypomania.

In a clinical study conducted to evaluate the effect of discontinuation of dapoxetine after 62 days of 60 mg (daily or as needed) in patients with premature ejaculation, no signs of withdrawal were found. After transferring patients to placebo after taking daily dapoxetine, only mild withdrawal symptoms were found in the form of mild to moderate insomnia and dizziness. Similar results were obtained in another double-blind clinical study with a one-week period to evaluate withdrawal effects after 24 weeks of 30 or 60 mg as needed.

Influence on the ability to drive vehicles, mechanisms and engage in other activities that require increased concentration. When taking dapoxetine, cases of dizziness, impaired attention, fainting, blurred vision, drowsiness have been described. The patient should be warned about the need to avoid situations in which injury is possible, including driving a car and operating dangerous machinery.

At a temperature not exceeding 25 ° C.

Keep out of the reach of children.