Primaxetin

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Primaxetin: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application of pregnancy and lactation
10. Use in childhood
11.disorders of renal function
12.abnormal liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Primaxetine

ATX code: G04BX14

Active ingredient: dapoxetine (Dapoxetine)

Producer: Obolensk JSC pharmaceutical company (Russia)

Description and photo update: 2018-27-07

Prices in pharmacies: from 490 rubles.

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Primaxetin is a drug for the treatment of premature ejaculation.

Release form and composition

Dosage form - film-coated tablets: round, biconvex, gray; the cross section shows the core of almost white or white color (3, 6 and 10 pcs. in blisters, 1 or 2 packs in a cardboard box and instructions for the use of Primaxetin).

Composition of 1 tablet:

active substance: dapoxetine (in the form of hydrochloride) - 30 or 60 mg;
auxiliary components: croscarmellose sodium, microcrystalline cellulose, lactose monohydrate, magnesium stearate, colloidal anhydrous silicon dioxide;
composition of the film shell: titanium dioxide, macrogol 6000 (polyethylene glycol 6000), hypromellose (hydroxypropyl methylcellulose), dyes of iron oxide yellow and iron oxide black.

Pharmacological properties

Pharmacodynamics

The mechanism of action of dapoxetine is presumably due to its ability to inhibit the reuptake of serotonin by neurons and subsequently enhance the effect of neurotransmitters on pre- and postsynaptic receptors.

The mechanism of ejaculation is regulated primarily by the sympathetic nervous system. The stimulus that triggers ejaculation is generated in the spinal reflex center, controlled through the brain stem by several nuclei, including the preoptic and paraventricular. Postganglionic sympathetic nerve fibers innervate the muscles of the bladder neck and urethra, the prostate gland, the vas deferens and seminal vesicles, and cause their coordinated contraction to achieve ejaculation.

Primaxetin increases the latency period and reduces the duration of reflex impulses of motor neurons of the perineal ganglia, thereby affecting the ejaculation reflex.

Pharmacokinetics

After oral administration, dapoxetine is rapidly absorbed from the gastrointestinal tract. The maximum plasma concentration (Cmax) reaches after 1-2 hours. After a single intake of Primaxetin on an empty stomach in doses of 30 and 60 mg, Cmax of the drug is, respectively, 297 ng / ml (after 1.01 hours) and 498 ng / ml (after 1.27 hours).

When taken simultaneously with fatty foods, the degree of absorption of dapoxetine does not change, however, Cmax decreases by 10%, the time to reach Cmax and AUC (area under the concentration-time curve) increases by 12%. These changes have no clinical significance, therefore, pills can be taken without reference to the regimen and diet.

The absolute bioavailability ranges from 15% to 76% (average 42%).

The connection of dapoxetine with plasma proteins is more than 99%, its active metabolite desmethyldapoxetine is 98.5%. The drug is quickly distributed throughout the body. The volume of distribution at steady state is 162 liters.

According to in vitro studies, dapoxetine is probably metabolized by many liver and kidney enzymes, especially CYP3A4, CYP2D6, flavin-containing renal monooxygenase. In a clinical study of metabolism ¹⁴C-dapoxetine has been found that after oral administration, dapoxetine is actively metabolized mainly by N-demethylation, N-oxidation, glucuronization, hydroxylation of the naphtho group, and addition of the sulfo group. Also found signs of presystemic metabolism in the liver. The main components that circulate in blood plasma are inactive dapoxetine N-oxide and intact dapoxetine. Didezmethyldapoxetine and desmethyldapoxetine were also found, but their amount is no more than 3% of the total concentration of circulating metabolites. According to in vitro data, didesmethyldapoxetine is less active than dapoxetine, approximately 2 times, and the activity of desmethyldapoxetine is comparable to that of dapoxetine. The AUC and Cmax of unbound desmethyldapoxetine are 50% and 23% of unbound dapoxetine, respectively.

Unchanged dapoxetine was not found in urine, its metabolites are excreted mainly in the form of conjugates. The elimination of the drug occurs quickly, as evidenced by its low concentration in the blood plasma 24 hours after taking Primaxetin - no more than 5% of the maximum concentration. The accumulation of the drug with daily intake is minimal.

The final half-life after taking the drug inside is approximately 19 hours.

Pharmacokinetics in special cases:

race: statistically significant differences in indicators in Hispanics, patients of European, Negroid and Mongoloid races when taking dapoxetine at a dose of 60 mg were not revealed. In Japanese, comparison of pharmacokinetics showed higher AUC and Cmax values by 10–20% compared with Europeans, which is due to lower body weight, but a significant difference in the severity of the clinical effect is not expected;
elderly age (from 65 years): significant spills of pharmacokinetic parameters after a single dose of Primaxetin at a dose of 60 mg were not identified. The average values of AUC and terminal half-life, respectively, are 12% and 46% higher than in younger men;
impaired renal function: no dependence of the pharmacokinetics of dapoxetine on creatinine clearance (CC) after a single administration of Primaxetine at a dose of 60 mg in patients with weak (CC 50-80 ml / min), moderate (CC 30-49 ml / min) and severe (CC <30 ml / min) impaired renal function. In patients with severely impaired renal function, the AUC is approximately 2 times higher than in those with normal renal function. Clinical experience with the use of Primaxetin in severe renal impairment is limited. In patients on hemodialysis, the pharmacokinetics of dapoxetine have not been studied;
liver dysfunction: the pharmacokinetic parameters of the drug in patients with mild hepatic dysfunction do not change. In moderate disorders (class B according to the Child-Pugh classification), the Cmax and AUC of dapoxetine are increased by 55% and 120%, respectively, the Cmax of the unbound active fraction of dapoxetine does not change, and the AUC is doubled. In severe liver dysfunctions, the AUC of the active fraction of dapoxetine increases several times, the Cmax of unbound dapoxetine does not change, the AUC increases more than 3 times;
CYP2D6 polymorphism: in patients with low CYP2D6 activity after a single dose of Primaxetine at a dose of 60 mg, Cmax and AUC of dapoxetine are higher by 31% and 36%, respectively, Cmax of desmethyldapoxetine is increased by 98%, AUC is increased by 161%, the final half-life increases on average by 2.4 hours compared with patients who have a high activity of the isoenzyme CYP2D6. Cmax of the active fraction of dapoxetine increased by 46%, AUC - by 90%. Such changes in the pharmacokinetics of the drug may lead to an increase in the incidence and severity of dose-dependent side effects. The safety of Primaxetine in patients with low CYP2D6 activity is questionable while taking other drugs that can inhibit the metabolism of dapoxetine (active and moderately active inhibitors of CYP3A4). In patients with ultra-high CYP2D6 activity, the plasma concentrations of dapoxetine and desmethyldapoxetine are expected to be reduced.

Indications for use

Primaxetin is used to treat premature ejaculation in men aged 18–64 years.

Contraindications

Absolute:

severe renal dysfunction;
moderate to severe liver dysfunction;
severe heart disease, for example, NYHA functional class II – IV heart failure, valvular disease or severe coronary artery disease, cardiac conduction disorders (sick sinus syndrome or grade II – III AV blockade) in the absence of a permanent pacemaker;
lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
age up to 18 years;
concomitant use of active CYP3A4 inhibitors (eg, nefazodone, saquinavir, itraconazole, ketoconazole, nelfinavir, telithromycin, ritonavir, atazanavir);
the period of use of monoamine oxidase (MAO) or thioridazine inhibitors and within 14 days after their cancellation (MAO / thioridazine inhibitors can be taken no earlier than 7 days after Primaxetin is discontinued);
the period of use of selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SSRIs), tricyclic antidepressants and other drugs with serotonergic action (for example, St. John's wort, tryptans, lithium, linezolid, L-tryptophan drugs) within 14 days after their cancellation (these drugs can be used no earlier than 7 days after the cancellation of Primaxetin);
hypersensitivity to any component of the drug.

It is recommended to avoid taking Primaxetin in patients with a history of established or suspected orthostatic hypotension, mania / hypomania, or bipolar disorder.

Relative contraindications (special care is required during the period of taking Primaxetin tablets):

weak and moderate renal dysfunction;
a history of bleeding disorders or bleeding;
the combined use of drugs that affect platelet aggregation (for example, anticoagulants, phenothiazines, atypical antipsychotics, acetylsalicylic acid or other non-steroidal anti-inflammatory drugs);
simultaneous use of powerful inhibitors of the CYP2D6 isoenzyme or moderate inhibitors of CYP3A4 in the case of genotypically low activity of the CYP2D6 isoenzyme;
simultaneous use of moderate inhibitors of CYP3A4 in the case of genotypically high activity of this isoenzyme.

Primaxetin, instructions for use: method and dosage

Primaxetin tablets should be taken orally, swallowed whole and washed down with at least 1 full glass of water. Food intake does not affect the activity of the drug.

The recommended starting dose for men 18–64 years of age is 30 mg. It should be taken 1-3 hours before the time of the expected sexual intercourse. If the effect is insufficient, but provided that the drug is well tolerated, an increase in the dose to 60 mg is allowed. It is recommended to take Primaxetin no more than once every 24 hours.

After 4 weeks of therapy or after taking 6 doses, the doctor evaluates the risks and benefits of the treatment and decides on the advisability of further use of the drug.

Patients with low CYP2D6 activity and men taking active CYP2D6 inhibitors should be careful when increasing the dose of Primaxetine from 30 mg to 60 mg.

With the simultaneous use of moderately active CYP3A4 inhibitors, the dose of Primaxetin should not exceed 30 mg. Primaxetin is contraindicated for use during therapy with active CYP3A4 inhibitors.

Side effects

The following side effects have been reported in clinical trials, were observed frequently and were dose-dependent when taking Primaxetin 30 and 60 mg doses, 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 (2.0% and 4.1%) … Interruption of treatment was required mainly due to severe nausea (in 2.2% of patients) and dizziness (in 1.2%).

Adverse reactions noted in clinical trials:

from the digestive system: often - dry mouth, abdominal pain, stomach discomfort, flatulence, diarrhea, constipation, bloating, dyspepsia, vomiting;
from the central nervous system: very often - dizziness, headache; often - paresthesia, tremor, impaired concentration, drowsiness; infrequently - a perversion of taste, akathisia, postural dizziness, fainting (including vasovagal), depression of consciousness, sedation, hypersomnia, fainting, lethargy; rarely - sudden falling asleep, dizziness during exercise;
mental disorders: often - unusual dreams, anxiety, agitation, anxiety, decreased libido; infrequently - bruxism, sleep disorders, nightmares, initial insomnia, intrasomnic disorder, mood swings, depressed mood, pathological thinking, apathy, indifference, nervousness, euphoria, somatosensory amplification, disorientation, confusion, depression, anorgasmia, loss of libido;
on the part of the cardiovascular system: often - hot flushes; infrequently - lowering blood pressure, sinus bradycardia, systolic hypertension, tachycardia, cessation of sinus node activity; rarely - hot flashes;
from the respiratory system: often - yawning, nasal congestion;
from the reproductive system: often - erectile dysfunction; infrequently - violation of orgasm (including anorgasmia), paresthesia of the male genitals, lack of ejaculation;
from the organ of hearing: often - ringing in the ears; infrequently - vertigo;
on the part of the organ of vision: often - blurred vision; infrequently - blurred vision, pain in the eye area, mydriasis;
from the skin and subcutaneous tissues: often - hyperhidrosis; infrequently - itching, cold sweat;
general reactions: often - irritability, weakness; infrequently - a feeling of malaise, anxiety, a feeling of heat, asthenia, a feeling of intoxication;
laboratory indicators: often - increased blood pressure; infrequently - an increase in diastolic blood pressure, an increase in orthostatic blood pressure, an increase in heart rate.

In clinical studies with Holter monitoring of cardiac function, cases of syncope with loss of consciousness, bradycardia or sinus arrest have been reported. Their development was associated with the administration of Primaxetin. In most cases, they occurred within the first 3 hours after taking the first dose or were associated with medical procedures (for example, blood sampling, blood pressure measurements, changes in body position). Fainting was often preceded by prodromal symptoms.

In patients receiving SSRIs for the treatment of chronic depressive disorders, in the case of a sudden withdrawal of the drug after prolonged use, the following symptoms were noted: insomnia, confusion, agitation, irritability, emotional lability, headache, dizziness, dysphoric state, hypomania, anxiety, sensory disturbances (for example, paresthesia), lethargy. According to the results of studies of the safety of dapoxetine, when the therapy was discontinued after 62 days, there were no signs of withdrawal syndrome. After transferring the patient to placebo after daily dapoxetine intake, only mild to moderate insomnia and dizziness were reported. Similar results were obtained in another double-blind controlled study with a one-week period evaluating withdrawal effects after 24 weeks of dapoxetine on demand at 30 and 60 mg doses.

Overdose

Overdose cases have not been described in clinical studies.

When taking Primaxetin at a dose of 240 mg (two doses of 120 mg with a break of 3 hours), there were no unexpected side effects. Symptoms of an SSRI overdose are manifested mainly by serotonergic reactions: tremor, drowsiness, dizziness, agitation, tachycardia, gastrointestinal disorders (nausea, vomiting).

In case of overdose, if necessary, supportive therapy is performed. Dapoxetine binds significantly to plasma proteins and is characterized by a large volume of distribution, so hemoperfusion, dialysis, forced diuresis and blood transfusion are unlikely to be effective. The specific antidote for Primaxetin has not been established.

special instructions

Primaxetin is indicated for use only in men for the treatment of premature ejaculation. There are no data on delayed ejaculation, and the safety of dapoxetine in men without premature ejaculation has not been established.

The frequency of syncope registered in clinical studies with the participation of healthy volunteers depended on the individual characteristics of patients and varied in the range of 0.06–0.64%. In some cases, they were preceded by prodromal symptoms (nausea, sweating, dizziness, or lightheadedness in the head). When Primaxetin was taken at a dose of 30 mg, nausea was noted with a frequency of 11%, dizziness - 5.8%, hyperhidrosis - 0.8%. When taking the drug at a dose of 60 mg, these indicators were respectively 21.2%; 11.7% vs. 1.5%. Syncope and prodromal symptoms were dose-dependent. According to the research results, syncope was regarded as having a vasovagal nature. In most cases, they occurred within the first 3 hours after taking the first dose, or were associated with medical procedures,conducted in a clinical setting (for example, taking a blood sample, measuring blood pressure, abrupt changes in body position). Fainting was often preceded by possible prodromal symptoms, which also occurred in the first 3 hours after dapoxetine administration.

Considering the above, the doctor should warn the patient that at any time during the period of taking Primaxetin, fainting may develop, both with and without prodromal symptoms. To reduce the risk of injury from a fall due to loss of consciousness, it is important for the patient to know how to recognize the symptoms of these side effects. If they occur, a man should lie down so that his head is below the level of the body, or sit down and lower his head between his knees. It is necessary to remain in this position until the symptoms disappear.

Cases of orthostatic hypotension in men taking Primaxetin have been described. The physician should inform the patient about possible prodromal symptoms of postural hypotension (for example, a feeling of lightness in the head immediately after standing up). In such a case, the man should also take a lying or sitting position as described above and remain in it until the symptoms disappear. In this case, it is recommended to avoid getting up suddenly after prolonged lying / sitting. Patients receiving vasodilators (for example, nitrates, alpha-blockers or PDE5 inhibitors) have reduced tolerance to the orthostatic effect of dapoxetine, so they need to take Primaxetine with caution.

With the development of fainting or any other reactions from the central nervous system, potentially traumatic situations should be avoided, including driving a car and working with complex mechanisms.

Primaxetine may increase the neuro-cardiogenic side effects of ethanol (including syncope) and its effects on the central nervous system, thereby increasing the risk of injury. In this regard, during the period of taking the drug, it is strongly recommended to refrain from drinking alcoholic beverages.

Do not take Primaxetin at the same time as drugs. With the combined use of drugs with serotonergic activity [for example, ketamine, d-lysergic acid diethylamide, methylenedioxymethamphetamine (ecstasy)], potentially serious reactions may develop, including hyperthermia, arrhythmia, serotonin syndrome. Concomitant use of sedatives (such as benzodiazepines or opiates) can increase dizziness and drowsiness.

In clinical studies of the efficacy and safety of dapoxetine, patients with diseases of the cardiovascular system did not participate. Patients with organic vascular and heart diseases have an increased risk of undesirable consequences of fainting. However, to date, it has not been reliably established whether this risk applies to vasovagal syncope.

If symptoms of mania / hypomania or bipolar disorder develop, Primaxetin should be withdrawn immediately.

SSRIs can lower the seizure threshold, so the drug is not recommended for patients with unstable epilepsy. Controlled epilepsy requires careful monitoring. If seizures develop, dapoxetine should be discontinued.

Primaxetin is not intended for the treatment of mental disorders (such as depression, schizophrenia, etc.). If a man has signs of depression, an examination should be made before taking the drug to rule out the presence of an undiagnosed depressive disorder. Dapoxetine should not be taken in combination with antidepressants. At the same time, patients are highly discouraged from discontinuing therapy for anxiety or depression in order to start taking Primaxetin.

If during the treatment period any thoughts or sensations that cause anxiety, or signs of depression appear, the drug should be discontinued and the doctor should be immediately informed of your condition.

Influence on the ability to drive vehicles and complex mechanisms

Primaxetin may cause dizziness, blurred vision, drowsiness, impaired attention, fainting. In this regard, patients are advised to refrain from performing potentially hazardous activities.

Application during pregnancy and lactation

Primaxetin is not intended for use in women.

The limited results of clinical trials do not suggest a possible negative effect of dapoxetine taken by a man on a partner's pregnancy.

Pediatric use

Primaxetin is contraindicated in children and adolescents under 18 years of age.

With impaired renal function

mild and moderate disturbances: dose adjustment of Primaxetin is not required, but therapy should be carried out with caution;
severe disorders: the drug is contraindicated.

The pharmacokinetics of dapoxetine in patients requiring hemodialysis have not been studied.

For violations of liver function

mild violations: dose adjustment is not required;
moderate to severe impairment (Child-Pugh classes B and C): Primaxetin is contraindicated.

Use in the elderly

Primaxetin is used in patients up to 64 years old inclusive.

Drug interactions

MAO inhibitors: it is possible to change the mental state (including strong agitation, progressing to delirium and coma), the development of serious and even fatal interaction reactions (such as myoclonus, rigidity, hyperthermia, instability of the autonomic system);
thioridazine: there is an inhibition of its metabolism and an increase in concentration, as a result of which it is possible to increase the lengthening of the QTc interval;
drugs with serotonergic action: the frequency of serotonergic side effects increases;
drugs acting on the central nervous system: interactions with Primaxetin have not been studied, caution should be exercised when using them together;
inhibitors of CYP2D6, CYP3A4 and flavin-containing monooxygenase: may decrease the clearance of dapoxetine;
active inhibitors of CYP3A4 (ketoconazole, telithromycin, nelfinavir, atazanavir, nefazodone, saquinavir, ritonavir, itraconazole): a high risk of a significant increase in the systemic effect of dapoxetine, especially in patients who do not have a functionally active enzyme CYP2D6;
moderately active inhibitors of CYP3A4 (amprenavir, clarithromycin, verapamil, diltiazem, fluconazole, erythromycin, aprepitant, fosamprenavir): a significant increase in the level of systemic action of dapoxetine is possible, especially in patients with low CYP2D6 activity;
active inhibitors of CYP2D6 (for example, fluoxetine): the Cmax and AUC of dapoxetine increase, especially in patients with low CYP2D6 activity, which may lead to an increase in the frequency and severity of side effects that are dose-dependent (caution should be exercised when increasing the dose of Primaxetine to 60 mg);
alpha-blockers, PDE5 inhibitors (tadalafil, sildenafil): patients' tolerance to orthostatic hypotension may decrease;
drugs metabolized by CYP2D6 (for example, desipramine): their maximum concentration in blood plasma increases, the clinical significance of this phenomenon is probably low;
warfarin: the studies did not reveal significant changes in the pharmacological parameters of warfarin and dapoxetine, however, caution is advised when using them simultaneously;
Ethanol: Increases the frequency and severity of side effects such as drowsiness, dizziness, changes in judgment and slow reflexes, as well as neuro-cardiogenic adverse reactions such as fainting.

Analogs

An analogue of Primaxetin is Priligy.

Terms and conditions of storage

Store at temperatures up to 25 ° C out of reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Primaksetin

According to reviews, Primaxetin is effective when used according to indications. Patients note a significant increase in the duration of intercourse (2–3 times) and good tolerance to the drug, despite the large list of possible side effects in the instructions.

Price for Primaxetin in pharmacies

The cost of Primaxetin, coated 30 mg tablets, is 547–597 rubles. per pack of 6 pcs.

Primaksetin: prices in online pharmacies

Drug name

Price

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Primaxetin 30 mg film-coated tablets 6 pcs.

490 rbl.

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Primaxetin tablets p.p. 30mg 6 pcs.

527 r

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Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!