Generic Dapoxetine Hydrochloride Tablets are mainly used for men with premature ejaculation and erectile dysfunction (prolonged sexual intercourse), and are also effective for patients with bipolar disorder.
Indications】
必利勁 is indicated for the treatment of men aged 18 to 64 years with premature ejaculation (PE) who meet all of the following conditions.
1, persistent or repeated ejaculation before, during or shortly after vaginal penetration, and before sexual satisfaction due to minimal sexual stimulation;
2. Significant personal distress or interpersonal difficulties due to premature ejaculation (PE);
3. Poor ejaculatory control.
Dosage
Take orally. Pills should be swallowed intact. Patients are advised to take the medication with at least one full glass of water. Patients should try to avoid injuries caused by prodromal symptoms such as syncope or dizziness.
Adult males (18 to 64 years of age)
The recommended initial dose for all patients is 30 mg, which needs to be taken approximately 1 to 3 hours prior to sexual intercourse. The recommended maximum dosing frequency is once every 24 hours.
Pitocin can be taken before or after a meal
If a physician chooses to treat premature ejaculation with Pirenz, the risks and patient-reported benefits should be evaluated during the first 4 weeks of treatment with the drug or after 6 therapeutic doses to assess the patient’s risk-benefit balance and decide whether to continue treatment with Pirenz.
Older adults (65 years and older)
The safety and efficacy of Bilevelin in patients 65 years of age and older have not been evaluated, primarily because of the limited data available on the use of this product in this population (see Pharmacokinetics section).
Children and Adolescents
Brigantine is not intended for use in persons under 18 years of age.
Patients with renal impairment
No dose adjustment is required for the administration of Pirenzin in patients with mild or moderate renal impairment, but it should be taken with caution. Pirenzin is not recommended for use in patients with severe kidney injury (see Pharmacokinetics section).
Patients with liver injury
No dose adjustment is required for the use of Pirenzin in patients with mild hepatic injury; Pirenzin is contraindicated in patients with moderate and severe hepatic injury (Child-Pugh Class C).
Adverse Reactions
Syncope (characterized by loss of consciousness) has been reported in clinical trials, and the event is considered drug-related. Most cases occurred within 3 hours of dosing, after the first dose, or during study-related operations (e.g., blood draws, upright movements, and blood pressure measurements) performed in the clinic. Syncope is often preceded by prodromal symptoms. Upright hypotension has been reported in clinical trials.
The most common (≥5%) adverse drug reactions in clinical trials included headache, dizziness, nausea, diarrhea, insomnia, and fatigue. The most common events leading to discontinuation included nausea and vertigo.
[Contraindications].
1.Bilirubicin is contraindicated in patients with known hypersensitivity to dapoxetine hydrochloride or any excipients.
2. Piritin is contraindicated in patients with significant cardiac pathology [e.g., heart failure (NYHA class II-IV), conduction abnormalities not treated with a permanent pacemaker (grade 2 or 3 atrioventricular block or sick sinus syndrome), significant myocardial ischemia and valvular disease].
3. Bilirubicin should neither be used with monoamine oxidase inhibitors (MAOIs) nor within 14 days after discontinuation of monoamine oxidase inhibitor therapy. Likewise, monoamine oxidase inhibitors should not be used within 7 days after discontinuation of Pirenz (see Drug Interactions section).
4. Pirenzin should neither be used with thioridazine nor within 14 days after discontinuation of thioridazine therapy. Likewise, thioridazine should not be taken within 7 days after discontinuation of Bilitrin (see Drug Interactions section).
5. Pirenzin should not be used with selective 5-hydroxytryptamine reuptake inhibitors [selective 5-hydroxytryptamine reuptake inhibitors (SSRI), 5-hydroxytryptamine-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA)] or other drugs/herbs that have a 5-hydroxytryptamine effect [e.g., L-tryptophan, traprotan, tramadol, linezolid, lithium, onychomycin extract (Hypericum perforatum)], nor within 14 days of discontinuation of these drugs/herbs. Likewise, these drugs/herbs should not be taken within 7 days of discontinuation of 必利勁 (see Drug Interactions section).
6. Birelin is contraindicated in patients taking concomitant strong cytochrome P450 3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nafenavir, and atazanavir.
7.Bilirubicin is prohibited for use in patients with moderate and severe liver injury.
Precautions
1. General Precautions
Pirenzin should only be used in male patients with premature ejaculation. The safety of Pirenzin in men without premature ejaculation is not known, and there are no data on the delayed ejaculation effect of Pirenzin in this population.
Patients are advised not to take Pirenz with “recreational drugs” because of the unknown effects and the potential for serious adverse events.
2. Use of psychotropic controlled substances
Patients are advised not to take Pirenz with psychotropic controlled substances that have a stimulant effect. Psychotropic controlled substances with 5-hydroxytryptaminergic activity, such as ketamine, methamphetamine and lysergic acid diethylamide, may cause serious adverse reactions if taken concurrently with Pirenz.
These adverse reactions include, but are not limited to, cardiac arrhythmias, hyperthermia, and 5-hydroxytryptamine syndrome. Concurrent use of psychotropic controlled substances with sedative effects, such as narcotics and benzodiazepines, may aggravate drowsiness and dizziness.
3. Alcohol
The concomitant use of alcohol with 必利勁 may aggravate alcohol-related neurological recognition effects and may also aggravate neurocardiovascular adverse effects (e.g., syncope), thus also increasing the risk of accidental injury; therefore, patients are advised to avoid taking alcohol while taking 必利勁.
4.Syncope
The use of Pitocin may cause syncope or dizziness. Possible prodromal symptoms such as nausea, dizziness, lightheadedness, palpitations, weakness, confusion, and sweating generally occur within 3 hours of drug administration and often precede syncope. If a patient experiences possible prodromal symptoms, he or she should lie down immediately so that the head is lower than the rest of the body, or sit down and place the head between the knees until the symptoms disappear, and should be warned to avoid situations that could cause injury if syncope or other central nervous system (CNS) effects occur, including driving or operating dangerous machinery. The concomitant administration of alcohol with 必利勁 can increase the risk of unintentional injury by increasing the risk of neurocardiovascular adverse events (e.g., syncope). Therefore, patients are advised not to take alcohol while taking PILIPIN.
5. Patients with cardiovascular risk factors
Subjects with underlying cardiovascular disease were not enrolled in phase III clinical trials. Patients with underlying organic cardiovascular disease (e.g., documented outflow tract obstruction, valvular heart disease, carotid stenosis, and coronary artery disease) have an increased risk of adverse cardiovascular reactions resulting from syncope (cardiogenic syncope and other causes of syncope). There are insufficient data to demonstrate whether this increased risk can progress to the risk of vasovagal syncope in patients with underlying disease.
6. Upright hypotension
Upright hypotension has been reported in bed trials. The prescriber should inform the patient in advance that if there are possible prodromal symptoms (e.g., dizziness shortly after standing up), he or she should immediately lie down so that the head is lower than the rest of the body or sit down and place the head between the knees until the symptoms disappear. Prescribers should also advise patients that they should not stand up quickly after prolonged lying or sitting down.
In addition, caution should be exercised when prescribing Bilevel for patients taking medications with vasodilating effects (e.g., alpha-adrenergic receptor antagonists, nitrates, phosphodiesterase type 5 (PDE5 inhibitors)) because of the potential for decreased standing tolerance.
7. Moderate cytochrome P450 3A4 inhibitors
Concurrent administration of moderate cytochrome P450 3A4 inhibitors, such as erythromycin, clarithromycin, fluconazole, amiprenavir, furosemide, aripitant, verapamil, and diltiazem, is limited to 30 mg and is recommended with caution.
8.Strong cytochrome P450 2D6 inhibitors
Caution should be exercised when increasing the dose to 60 mg in patients taking concomitant strong cytochrome P450 2D6 inhibitors or known weak metabolizers of cytochrome P450 2D6, as this may result in increased exposure and may ultimately lead to a higher incidence and severity of dose-dependent adverse reactions.
9. Suicide/suicidal thinking
Short-term studies in children and adolescents with major depression and other psychiatric disorders have found that antidepressants (including selective 5-hydroxytryptamine reuptake inhibitors) can increase the risk of suicidal thinking and suicidal behavior compared to placebo.
Short-term studies did not confirm that antidepressants increased the risk of suicidal behavior compared with placebo in adults over 24 years of age. In clinical trials of Bilevel for premature ejaculation, there were no clear suicidal behaviors in first aid treatment.
10. Mania
Pirenz should not be used in patients with a history of mania/hypomania or bipolar disorder, and Pirenz should be discontinued in any patient with symptoms of these disorders.
11.Epilepsy
Because selective 5-hydroxytryptamine reuptake inhibitors may lower the threshold for seizures, 必利劲 should be discontinued in any patient with seizures and should be avoided in patients with unstable epilepsy. Patients whose epilepsy has been controlled should be monitored closely.
12. Use in children and adolescents under 18 years of age
Pirenz should not be used in people under 18 years of age.
13. Combined depression and psychiatric disorders
Men with signs and symptoms of depression should be evaluated to rule out undiagnosed depressive disorders prior to the administration of 必利勁. Concomitant use of antidepressants, including selective 5-hydroxytryptamine reuptake inhibitors and selective norepinephrine reuptake inhibitors, is prohibited. Interrupting treatment for depression and anxiety to take PILIGIN for premature ejaculation is not recommended. Pirenz is not indicated for psychiatric disorders and should not be used in men with psychiatric disorders (e.g., schizophrenia) or in patients with psychiatric disorders combined with depression because exacerbation of depression-related symptoms cannot be ruled out. This may be the result of an underlying psychiatric disorder or may be the result of pharmacological treatment. If the signs and symptoms of depression worsen, the use of BILIPA should be discontinued.
14. Bleeding
Abnormal bleeding has been reported during treatment with selective 5-hydroxytryptamine reuptake inhibitors. Caution should be exercised when patients are taking PILIPIN, especially those taking concomitant medications known to affect platelet function (e.g., atypical antipsychotics and phenothiazines, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs [NSAIDs], antiplatelet agents) or anticoagulants (e.g., warfarin), and patients with a history of bleeding or clotting disorders.
15. Renal injury
Bilevelin is not recommended for patients with severe renal impairment and should be used with caution in patients with mild or moderate renal impairment.
16. Discontinuation effects
Abrupt discontinuation of long-term treatment with selective 5-hydroxytryptamine reuptake inhibitors for chronic depression has been reported to cause the following symptoms: anxiety, irritability, euphoria, dizziness, sensory abnormalities (i.e., sensory confusion, such as electroconvulsive perception), anxiety, confusion, headache, drowsiness, mood swings, insomnia, and hypomania.
17.Ocular disorders
As with other selective 5-hydroxytryptamine reuptake inhibitors, there is an association between the use of PILIPIN and some ocular reactions, such as pupil dilation and eye pain. Patients with elevated intraocular pressure or at risk of closed-angle glaucoma should use Piritin with caution.
18. Keep out of the reach of children.
For Pregnant and Lactating Women
Women are not suitable for the use of Pirenzin.
Pregnancy.
No evidence of teratogenicity, embryotoxicity, or fetal toxicity was found in rats or rabbits receiving up to 100 mg/kg (rats) or 75 mg/kg (rabbits) of pirenzine. Based on the limited observational data currently available from the clinical trials database, there is no evidence of maternal pregnancy effects associated with dapoxetine administration. A sufficient number of well-controlled studies in pregnant women have not been conducted.
Lactation.
It is not clear whether dapoxetine or its metabolites can be secreted in human breast milk.
Pediatric Use: Bilevelin should not be used in people under 18 years of age.
Geriatric Use]
The safety and efficacy of Bilirubicin in patients 65 years of age and older have not been evaluated, primarily because of the extremely limited data on the use of this product in this population.
Analysis of a single dose clinical pharmacology study using 60 mg of dapoxetine hydrochloride showed no significant differences in pharmacokinetic parameters (Cmax, AUCinf, Tmax) between healthy elderly men and healthy young men.
Drug Interactions]
1. The possibility of interaction with monoamine oxidase inhibitors
Severe (sometimes fatal) reactions have been reported in patients taking a selective 5-hydroxytryptamine reuptake inhibitor plus a monoamine oxidase inhibitor (MAOI), including hyperthermia, tonicity, myoclonus, autonomic instability with possible rapid fluctuations in vital signs and altered mental status, including extreme euphoria that progresses to delirium and coma. These reactions have also been reported in patients who have recently discontinued a selective 5-hydroxytryptamine reuptake inhibitor and started treatment with a monoamine oxidase inhibitor. Some cases exhibit features similar to those of the malignant syndrome of nerve blockers. Data from the combined use of selective 5-hydroxytryptamine reuptake inhibitors and monoamine oxidase inhibitors in animal models suggest that these drugs may have synergistic effects in elevating blood pressure and inducing behavioral arousal. Therefore, 必利勁 should not be used in combination with monoamine oxidase inhibitors or within 14 days after discontinuation of monoamine oxidase inhibitor therapy. Similarly, monoamine oxidase inhibitors should not be used within 7 days after discontinuation of Pirenzine (see contraindications section).
2. Potential for interaction with thioridazine
Thioridazine alone can prolong the QTc interval, which is associated with severe ventricular arrhythmias. Some drugs that inhibit cytochrome P450 2D6 isoenzymes, such as pirenz, can inhibit the metabolism of thioridazine, leading to an increase in thioridazine concentration, which increases the prolongation of the QTc interval. Pirenzin should not be used in combination with thioridazine or within 14 days of stopping thioridazine therapy. Likewise, thioridazine should not be used within 7 days after discontinuation of pirenz (see contraindication section).
3. Drugs/herbs with 5-hydroxytryptamine effects
As with other selective 5-hydroxytryptamine reuptake inhibitors, the combination of pirenzine with drugs/herbs with 5-hydroxytryptamine effects (including monoamine oxidase inhibitors, L-tryptophan, traprotan, tramadol, linezolid, selective 5-hydroxytryptamine reuptake inhibitors, 5-hydroxytryptamine-norepinephrine reuptake inhibitors, lithium, and onychomycin extract (Hypericum perforatum)) may result in the development of 5- serotonin effects. Pirenz should not be used in combination with other selective 5-hydroxytryptamine reuptake inhibitors, monoamine oxidase inhibitors, or other drugs/herbs with 5-hydroxytryptamine-related effects, nor should it be taken within 14 days of discontinuation of these drugs/herbs. Likewise, these drugs/herbs should not be taken within 7 days of discontinuation of Bilevel (see contraindications section).
4. Central nervous system active drugs
The combination of pirenz and CNS-active drugs has not been systematically evaluated in patients with premature ejaculation. Therefore, patients should be treated with caution if the concomitant use of Pirenz with such drugs is required.
5. Effects of drug combinations on dapoxetine hydrochloride
In vitro studies in human liver, kidney and intestinal microsomes have shown that dapoxetine is mainly metabolized by cytochrome P450 2D6, cytochrome P450 3A4 and flavin-containing monooxygenase 1 (FMO1). Therefore, inhibitors of these enzymes may reduce the clearance of dapoxetine.
6.Potent cytochrome P450 3A4 inhibitors
Ketoconazole (200 mg twice daily for 7 days) was able to increase the Cmax and AUCinf of dapoxetine (60 mg single dose) by 35% and 99%, respectively. Considering the effects of free dapoxetine and desmethyl dapoxetine, the maximum blood concentration of the active fraction (the sum of free dapoxetine and desmethyl dapoxetine) may be increased by approximately 25% and the AUC may be doubled if a strong inhibitor of cytochrome P450 3A4 is administered. Such an increase may be significant in certain patients, including primarily those lacking the cytochrome P450 2D6 functional enzyme, i.e., weak metabolizers of cytochrome P450 2D6, or those coadministered with strong inhibitors of cytochrome P450 2D6. Therefore, Bilevel is contraindicated in patients taking concomitant ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nafenavir, atazanavir, etc.
7.Moderate cytochrome P450 3A4 inhibitor
Concomitant administration of moderate cytochrome P450 3A4 inhibitors, like erythromycin, clarithromycin, fluconazole, amiprenavir, furosemivir, aripitant, verapamil, and diltiazem, may also significantly increase exposure to dapoxetine and desmethyl dapoxetine, especially in weak metabolizers of cytochrome P450 2D6. Therefore, if combined with any of these drugs the maximum dose of Bilirubicin taken is limited to 30 mg and caution is advised.
8.Potent inhibitors of cytochrome P450 2D6
When fluoxetine (60mg/day for 7 days) was combined with dapoxetine (60mg single dose), the Cmax and AUCinf of the latter increased by 50% and 88%, respectively. Considering the effects of free dapoxetine and desmethyl dapoxetine, the maximum blood concentration of the active fraction (the sum of free dapoxetine and desmethyl dapoxetine) may be increased by approximately 50% and the AUC may be doubled if a strong inhibitor of cytochrome P450 2D6 is administered.
This elevation in the maximum blood concentration and AUC of the active fraction is similar to that expected in cytochrome P450 2D6 weak metabolizers and may increase the incidence and severity of dose-dependent adverse events. Therefore, careful consideration should be given to increasing the dose to 60 mg in patients taking potent inhibitors of cytochrome P450 2D6 and known weak metabolizers of cytochrome P450 2D6.
9. Type 5 phosphodiesterase inhibitors
A single-dose crossover study evaluated the pharmacokinetics of dapoxetine (60 mg) when combined with tadalafil (20 mg) and sildenafil (100 mg). Tadalafil did not affect the pharmacokinetics of dapoxetine. Sildenafil can mildly alter the pharmacokinetics of dapoxetine (22% increase in AUCinf and 4% increase in Cmax), but this effect is not clinically significant. However, due to the potential for decreased standstill tolerance, bilirubicin should be used with caution in patients who are using a type 5 phosphodiesterase inhibitor.