Priligi® (Priligy®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceDapoxetineDapoxetine
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  • Priligi®
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    Berlin-Chemie, AG     Germany
  • Primaxetine®
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    OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC     Russia
    • Dosage form: & nbspfilm-coated tablets
    Composition:

    1 tablet, film-coated, 30 mg dosage contains:

    active substance: dapoxetine hydrochloride 33.6 mg in terms of dapoxetine 30 mg;

    Excipients: core tablet: mixture "MicroceLac 100" (75:25, lactose monohydrate: microcrystalline cellulose) 58.5 mg, croscarmellose sodium 4.00 mg, silicon dioxide colloid 2.50 mg, magnesium stearate 1.40 mg; tablet shell: opadray gray, mixture 4 (composed of lactose monohydrate, hypromellose, titanium dioxide (E171), triacetin, iron ferric oxide black (E172), iron oxide pigment yellow (E172)) 5.00 mg.

    1 tablet, film-coated, with a dosage of 60 mg contains:

    active substance: dapoxetine hydrochloride 67.2 mg in terms of dapoxetine 60 mg;

    auxiliary substances: Icore tablet: mixture "MicroceLac 100" (75:25, lactose monohydrate: microcrystalline cellulose) 117.0 mg, croscarmellose sodium 8.0 mg, silicon colloidal dioxide 5.00 mg, magnesium stearate 2.80 mg; tablet shell: opadray gray, mixture 3 (composed of lactose monohydrate, hypromellose, titanium dioxide (E171), triacetin, iron ferric oxide black (E172), iron oxide pigment yellow (E172)) 10.00 mg.

    Description:

    Dosage of 30 mg: round biconvex tablets, covered with a film shell of gray color, with the squeezed out inscription "30" inside the triangle on one side. On the cross section, the core of the tablet is white or almost white in color.

    Dosage of 60 mg: round biconvex tablets, covered with a film shell of gray color, with an embossed inscription "60" inside the triangle on one side. On the cross section, the core of the tablet is white or almost white in color.

    Pharmacotherapeutic group:ejaculation premature treatment
    ATX: & nbsp

    G.04.B.X.14   Dapoxetine

    G.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:

    Suction

    Dapoxetine is rapidly absorbed, and the maximum concentration in the blood plasma (FROMmOh) is achieved 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 foods moderately reduces FROMmOh dapoxetine (by 10%) and increases by 12% AUC (the area under the "concentration-time" curve) 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 Priligi® can be taken regardless of food intake.

    Distribution

    More 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.

    Metabolism

    Research in vitro We can assume that dapoxetine metabolized by many enzymes of the liver and kidneys, especially CYP2D6, CYP3A4 and flavin-containing monooxygenase (FMO1) kidney. In a clinical study in which metabolism was studied 14C-dapoxetine, dapoxetine After oral administration, it was actively metabolized mainly by N-oxidation, N-detylation, 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 studies in vitro it was found that dapoxetine-NThe 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. In the study in vitro It was found that desmethyldapoxetine is comparable in activity to dapoxetine, and didezmethyldapoxetine is about 2 times less active than dapoxetine. Exposition (AUC and CmOh) of unbound desmethyldapoxetine was 50% and 23% of unbound dapoxetine, respectively.

    Excretion

    Metabolites 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.

    Pharmacokinetics in specific patient categories

    Race

    A 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.A comparison of the pharmacokinetics of dapoxetine in Europeans and Japanese showed higher values ​​of Cmax and AUC (the area under the "concentration-time" curve) 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 in a dose of 60 mg did not reveal a significant difference in pharmacokinetics (CmOh, AUC0-∞ (area under the curve "concentration-time"), TmOh) in healthy elderly men and men of younger age.

    Mean values AUC0-∞ dapoxetine and the final half-life were higher by 12% and 46%, respectively, in elderly men compared to men of younger age, respectively.

    Impaired renal function

    A single dose of dapoxetine in a dose of 60 mg did not reveal a relationship between the clearance of creatinine and CmOh or AUC0-∞ (the area under the concentration-time curve) of dapoxetine in patients with a weak (creatinine clearance 50-80 ml / ml), moderately expressed (creatinine clearance from 30 to <50 ml / min) and severe (creatinine clearance <30 ml / min ) impaired renal function. AUC 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 function

    In 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) CmOh and AUC (the area under the concentration-time curve) of unbound dapoxetine was increased by 55% and 120%, respectively. FROMmOh unbound active fraction of dapoxetine was unchanged, a AUC (area under the curve "concentration-time") - increased by 2 times.

    In patients with severe impairment of liver function CmOh unbound dapoxetine was not changed, a AUC (the area under the concentration-time curve) of unbound dapoxetine was increased more than 3-fold. AUC (area under the concentration-time curve) of the active fraction was also increased several times.

    Polymorphism CYP2D6

    The concentration of dapoxetine in the blood plasma after a single dose of Priligi® in a dose of 60 mg in patients with low activity CYP2D6 was higher than in patients with high activity CYP2D6 (Cmax by about 31%, AUC0-∞ (the area under the concentration-time curve) is about 36%).Similarly, CmOh desmethyldapoxetine in patients with low activity CYP2D6 was increased by 98%, and AUC0-∞ (area under the concentration-time curve) by 161%. The average final half-life of dapoxetine was increased by 2.4 hours in patients with low isoenzyme activity CYP2D6 in comparison with patients with high isoenzyme activity CYP2D6. FrommOh The active fraction of dapoxetine was increased by -46%, a AUC (the area under the concentration-time curve) - by -90%. This increase may be accompanied by an increased frequency and severity of dose-related adverse events. Safety of Priligi® in patients with low activity CYP2D6 can raise doubts at simultaneous reception of other medicines, capable to brake a metabolism of a dapoxetine, in particular, active and moderately active inhibitors CYP3A4.

    It is expected that in patients with ultrahigh activity CYP2D6 concentrations of dapoxetine and desmethyldapoxetine in blood plasma will be reduced.

    Indications:

    The drug Priligi® is designed to treat premature ejaculation in men aged 18 to 64 years.

    Contraindications:

    - Hypersensitivity to dapoxetine hydrochloride or any auxiliary component of the drug;

    - severe heart disease (eg, heart failure II-IV class on NYHA, Cardiac conduction (atrioventricular conduction blockade of 2-3 degrees or weakness sinus syndrome) in the absence of a permanent pacemaker, severe coronary heart disease or valvular apparatus involvement);

    - 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 Priligi®;

    - simultaneous administration of thioridazine and within 14 days after discontinuation of its use. Similarly, thioridazine Do not take within 7 days after discontinuation of Priligi®;

    - simultaneous reception of serotonin reuptake (selective serotonin reuptake inhibitors - SSRIs) inhibitors, serotonin reuptake inhibitors and noradrenaline and tricyclic antidepressants) and other drugs with serotonergic action (e.g., L-tryptophan, triptans, tramadol, linezolid, lithium, preparations of St. John's wort (Hypericum perforatum) and within 14 days after discontinuation of these medications. Similarly, these drugs can not be taken within 7 days after discontinuation of Priligi®;

    - simultaneous administration with active inhibitors CYP3A4, for example, ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, atazanavir, etc .;

    - moderately severe and severe liver function disorders;

    - severe renal dysfunction;

    - children and adolescents under the age of 18;

    - lactose intolerance.

    If history of established or suspected orthostatic hypotension, as well as the presence of a history of mania / hypomania or bipolar disorder, drug treatment should be avoided.

    Carefully:

    - Weak or moderately severe renal dysfunction;

    - simultaneous use with potent inhibitors of isoenzyme CYP2D6 and moderate inhibitors CYP3A4 in patients with genotypically low isoenzyme activity CYP2D6 and patients with high isoenzyme activity CYP2D6 (in combination with moderate isoenzyme inhibitors CYP3A4);

    - simultaneous use with drugs that affect platelet aggregation, and with anticoagulants due to the risk of bleeding.

    Pregnancy and lactation:

    Priligi® is not suitable for use in women.

    Pregnancy

    Based 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.

    Lactation period

    It 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 Priligi® can be taken regardless of food intake.

    Adult men from 18 to 64 years old

    The 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 prescribing Priligi® for the treatment of premature ejaculation should assess the risk and benefit of using the drug after the first 4 weeks of treatment or after taking 6 doses and shoulddetermine the risk-benefit ratio for deciding whether to continue treatment with Priligi®.

    Patients with impaired renal function

    For patients with mild or moderate renal impairment, dose adjustment is not required, but caution is advisable. Priligi® is not recommended for patients with severe renal dysfunction.

    Patients with impaired hepatic function

    For patients with a weak violation of liver function, dose adjustment is not required. Prilidz® is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B and C).

    Patients with low activity CYP2D6, simultaneous administration with active inhibitors CYP2D6

    Caution should be exercised when increasing the dose of Priligi® to 60 mg in individuals with low CYP2D6 activity or in patients, while taking Prilij® with active CYP2D6 inhibitors.

    Patients receiving active or moderately active inhibitors CYP3A4

    Simultaneous reception of active inhibitors CYP3A4 is contraindicated. At simultaneous reception of preparation Priliji with moderately active inhibitors CYP3A4 dose of the drug 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 in the table below:

    Often

    (> 1/10)

    Often

    (1>1/100-<1/10)

    Infrequently

    (>1/1000-<1/100)

    Rarely

    (>1/10000- <1/1000)

    Mental disorders

    Anxiety, agitation, restlessness, unusual dreams, decreased libido

    Depression,

    depressed mood,

    a state of euphoria,

    mood changes,

    nervousness,

    indifference, apathy,

    confusion,

    disorientation,

    pathological thinking,

    somatosensory amplification,

    sleep disorders,

    initial insomnia,

    intrasomnia disorder,

    nightmares,

    bruxism, loss of libido, anorgasmia

    From the central nervous system

    Dizziness, headache

    Drowsiness, impaired concentration, tremor, paresthesia

    Fainting, including vasovagal syncope, postural dizziness, akathisia, taste distortion, hypersomnia, lethargy, sedation, depression of consciousness

    Dizziness during exercise, sudden falling asleep

    From the side of the organs of sight

    Blurred vision

    Mydriasis, pain in the eye area, impaired vision

    From the organs of hearing and labyrinth

    Tinnitus

    Vertigo

    From the side of the cardiovascular system

    "Flushes" of blood

    The cessation of activity of the sinus node,

    sinus bradycardia,

    tachycardia,

    lowering blood pressure,

    systolic hypertension,

    "Hot flushes" of heat

    From the respiratory system

    Nasal congestion, yawning

    From the gastrointestinal side tract

    nausea

    Diarrhea, vomiting, constipation, abdominal pain, indigestion, flatulence, stomach discomfort, bloating, dry mouth

    From the skin and subcutaneous tissues

    Hyperhidrosis,

    Itching, cold sweat

    On the part of the reproductive system:

    erectile disfunction

    Lack of ejaculation, violation of orgasm, including anorgasmia in men, paresthesia of male genital organs.

    General information state:

    Weakness, irritability.

    Asthenia, a feeling of heat, a sense of anxiety, a feeling of malaise, a feeling of intoxication

    Changes laboratory indicators

    Increase arterial pressures

    An increase in heart rate, an increase in diastolic blood pressure, an increase in orthostatic blood pressure

    Description of individual side effects

    Fainting with loss of consciousness, with bradycardia or the arrest of the sinus node, was observed in patients under Holter monitoring and were 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 cancellation

    With 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:

    In clinical studies, cases of overdose are not described.

    The use of Priligi® in a dose up to 240 mg (2 doses of 120 mg with an interval of 3 hours) did not cause unforeseen undesirable phenomena. In general, the symptoms of an SSRI overdose include serotonergic reactions, including drowsiness, gastrointestinal disorders (nausea, vomiting), tachycardia, tremors, agitation and dizziness.

    When 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 inhibitors

    Serious 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, Priligi® should not be taken concomitantly 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 Priligi®.

    Interaction with thioridazine

    Thioridazine lengthens the interval QTc, which is accompanied by ventricular arrhythmia. Preparations such as Priligi®, which inhibit the enzyme CYP2D6, apparently, inhibit the metabolism of thioridazine. It is expected that the resulting increase in the level of thioridazine will enhance the lengthening of the interval QTc. The drug Priligi® 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 Priligi®.

    Drugs that have a serotonergic effect

    As in the case of SSRIs, the use of Priligi® along with serotonergic drugs (including MAO-I, L-tryptophan, triptans, tramadol, linezolid, SSRIs, inhibitors of the seizure of serotonin and norepinephrine, lithium and preparations of St. John's wort (Hypericum perforatum) may increase the incidence of serotonergic side effects. Priligi® should not be taken concomitantly with other SSRIs, MAO-I and other serotonergic drugs and within 14 days after discontinuation of these medications.Similarly, these drugs can not be taken within 7 days after discontinuation of Priligi®.

    Drugs acting on the central nervous system

    The use of Priligi® along 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 hydrochloride

    Studies using microsomes of the liver, kidneys and intestines of humans in vitro showed that dapoxetine is metabolized predominantly CYP2D6, CYP3A4 and flavin-containing monooxygenase 1 (FMO1). Therefore, inhibitors of these enzymes can reduce the clearance of dapoxetine.

    Inhibitors CYP3A4

    Active inhibitors CYP3A4

    Admission ketoconazole at a dose of 200 mg 2 times a day for 7 days increased CmOh and AUC0-∞ (area under the concentration-time curve) of dapoxetine (60 mg once) by 35% and 99%, respectively. Taking into account the fraction of unbound dapoxetine and desmethyldapoxetine, Cmax active fraction (the sum of unbound dapoxetine and desmethyldapoxetine) in the presence of active inhibitors CYP3A4 can increase by about 25%, a AUC (the area under the "concentration-time" curve) can be doubled. This increase in CmOh and AUC (the area under the concentration-time curve) of the active fraction can be much more pronounced in the subpopulation of patients who do not have a functionally active enzyme CYP2D6, as well as with the simultaneous administration of active inhibitors CYP2D6.

    Priligi® should not be taken concomitantly with active inhibitors CYP3A4, for example, ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir and atazanavir.

    Moderately active inhibitors of CYP3A4

    Simultaneous reception of moderately active inhibitors CYP3A4, for example, erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil or diltiazem, can significantly increase the systemic exposure to dapoxetine and desmethyldapoxetine, especially in patients with low activity CYP2D6. The maximum dose of Priligi® taken concomitantly with these 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 CmOh and AUC0-∞ (area under the concentration-time curve) of dapoxetine (60 mg once) by 50% and 88% respectively. Taking into account the fraction of unbound dapoxetine and desmethyldapoxetine, CmOh active fraction (the sum of unbound dapoxetine and desmethyldapoxetine) in the presence of active inhibitors CYP2D6 can increase by about 50%, and AUC (the area under the "concentration-time" curve) can be doubled. This increase in CmOh and AUC (the area under the concentration-time curve) of the active fraction is close to that expected in patients with low activity CYP2D6 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 Prilij® to 60 mg in patients receiving active inhibitors CYP2D6, and in patients with low activity CYP2D6.

    Interaction with drugs metabolized by isoenzymes CYP1A and CYP 2B6

    Based on the comparative data Cmax dapoxetine when taking a dose of 60 mg and dapoxetine at 50% inhibition (IC50) isoenzyme CYP1A2 in vitro, it was concluded that the effect of dapoxetine on the concentration of concomitantly prescribed drugs is not expected,metabolized by this isoenzyme. The effect of dapoxetine on isoenzyme CYP2B6 has not been studied.

    Inhibitors of PDE5

    The 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 AUC0-∞ (the area under the concentration-time curve) and CmOh dapoxetine (respectively, 22% and 4%), which is considered clinically insignificant. Priligi® should be administered 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 drugs

    Tamsulosin

    Single and multiple administration of Priligi® 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. Also, the frequency of orthostatic hypotension did not change, which was the same with only tamsulosin and in a combination of tamsulosin with Prilij® 30 mg or 60 mg. Priligi® should be administered with caution to patients taking alpha-blockers, because of the possibly reduced tolerance of these patients to orthostatic hypotension.

    Drugs metabolized by CYP2D6

    Multiple taking Priligi® (60 mg / day for 6 days) increased CmOh and AUC0-∞ (the area under the concentration-time curve) 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 CYP2D6. The clinical significance of this is likely to be small.

    Drugs metabolized by CYP3A

    Multiple administration of Priligi® (60 mg / day for 6 days) reduced AUC0-∞ (area under the concentration-time curve) of midazolam (8 mg once) by about 20% (range -60% to + 18%). The clinical significance of this phenomenon in most patients is likely to be small. However, increased activity CYP3A may be of clinical importance in some patients taking drugs simultaneously metabolized in the main CYP3A, and having a narrow therapeutic window.

    Drugs metabolized by CYP2C19

    Multiple administration of Priligi® (60 mg / day for 6 days) did not affect the pharmacokinetics of omeprazole (40 mg once). Dapoxetine hardly affects the pharmacokinetics of other substrates CYP2C19.

    Drugs metabolized by CYP2C9

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

    Inhibitors of PDE5

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

    Warfarin

    Data on the effects of long-term taking of warfarin simultaneously with Priligi® is not available. It is recommended to be cautious when prescribing Priligi® 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).

    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 use of the drug Priligi® and ethanol increased drowsiness and significantly reduced the level of wakefulness when assessed by the patient. Admission of only ethanol and only Priligi® did not significantly change cognitive performance (reaction rate in the number recognition test and in the symbol replacement test) compared with placebo,However, the combination of ethanol with the Prilidge® preparation statistically significantly changed these parameters in comparison with only ethanol. Simultaneous reception of ethanol and Prilidz® increases the frequency and severity of such undesirable reactions as dizziness, drowsiness, slowing down of reflexes, changing judgments. The combination of alcohol with Priligi® can also enhance neurocardiogenic side effects, in particular the frequency of syncope, which increases the risk of accidental injury. Therefore, patients should be advised to refrain from drinking alcohol during treatment with Priligi®.

    Special instructions:

    Are common

    The drug Priligi® is intended 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.

    Ptogether with narcotic drugs

    Patients should be advised not to take Priligi ® with narcotic drugs. Simultaneous reception of Priligi® with drugs that have serotonergic activity, for example, 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 Priligi® together with sedatives such as opiates or benzodiazepines may increase drowsiness and dizziness.

    Ethanol

    The combination of Priligi® with alcohol can increase 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 Prilidge®.

    Fainting

    The frequency of syncope in clinical trials of Priligi® 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 receiving Priligi® received more prodromal symptoms than patients who received placebo, including nausea, dizziness / lightheadedness, and sweating.With a dose of Priligi® 30 mg, the incidence of nausea was 11.0%, the incidence of dizziness was 5.8%, and the hyperhidrosis rate was 0.8%. At a dose of Prilidz® 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 vasovagal 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 period of treatment with Priligi® 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 Priligi® with alcohol may increase neurocardiogenic side effects, including syncope, which increases the risk of accidental trauma; so patients should be advised to refrain from drinking alcohol during treatment with Priligi®.

    Patients with a risk of cardiovascular disease

    In 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 ejection of blood from cheart, valvular disease, stenosis of the carotid artery, coronary artery atherosclerosis) increased the risk of unwanted cardiovascular consequences of syncope of cardiac and other origin. However, at present there is insufficient data to determine whether this risk extends to vasovagal syncope in patients with cardiovascular disease.

    Orthostatic hypotension

    In 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, Priligi® should be administered with caution to patients taking vasodilator drugs (for example,alpha-adrenoblockers, nitrates, PDE5 inhibitors), because of the possible reduced tolerance of such patients to the orthostatic effect of the drug.

    Moderately active inhibitors CYP3A4

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

    Active inhibitors CYP2D6

    It is recommended to exercise caution when increasing the dose of Prilij® to 60 mg in patients receiving active inhibitors CYP2D6, and in patients with low activity CYP2D6, as this may increase the level of systemic effects of 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 with placebo. In adults over 24 years of this effect is not found.In clinical studies of the preparation Priligi ® for the treatment of premature ejaculation of clear data on the relationship of suicidal thoughts with treatment is not received.

    Mania

    Priligi® should not be taken to patients with a history of mania / hypomania or bipolar disorder, when symptoms of these diseases appear, the drug should be discontinued.

    Convulsions

    Due to the ability of SSRIs to reduce the convulsive threshold, Priligi® should be avoided in patients with unstable epilepsy, the drug should be withdrawn if seizures occur. Patients with controlled epilepsy require careful monitoring.

    Admission in children and adolescents under the age of 18

    Prilij® should not be taken to patients younger than 18 years of age.

    Concomitant depression and mental disorders

    If the patient has signs and symptoms of depression prior to the use of Priligi®, a check should be performed to exclude the presence of undiagnosed depressive disorder. Priligi® 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 to start treatment with Priligi®. Priligi® 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, Prilig® should be discontinued.

    Bleeding

    When using SSRIs, cases of bleeding are described. It is advisable to take caution when taking Priligi® along with drugs that affect platelet function (for example, atypical antipsychotics, phenothiazines, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants), as well as in patients with bleeding or history of clotting.

    Impaired renal function

    Priligi® is not recommended for patients with severe renal dysfunction, patients with moderate to mild renal impairment should be cautious.

    The withdrawal syndrome

    There is evidence that the abrupt withdrawal of SSRIs, long used for the treatment of chronic depressive disorders, leads to the following symptoms: mood reduction, irritability, agitation, dizziness, sensitivity disorders (eg paresthesia in the form of an electric shock), anxiety, confusion, headache, lethargy, emotional instability, insomnia, hypomania.

    In a clinical study conducted to assess the effect of discontinuing Priligi® after 62 days of 60 mg doses (daily or on demand) in patients with premature ejaculation, no signs of withdrawal have been identified. After transferring patients to placebo after daily administration of Priligi®, only minor withdrawal symptoms were observed 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:

    3 or 6 tablets per blister.

    For 1 blister, along with instructions for medical use 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 expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002154
    Date of registration:25.07.2013
    Date of cancellation:2018-07-25
    The owner of the registration certificate:Berlin-Chemie, AGBerlin-Chemie, AG Germany
    Manufacturer: & nbsp
    Representation: & nbspBERLIN-CHEMI / MENARINI PHARMA GmbH BERLIN-CHEMI / MENARINI PHARMA GmbH Germany
    Information update date: & nbsp27.12.2015
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