Wonder

Wonder

dapoxetine

Manufacturer:

Kusum

Distributor:

JDS
Full Prescribing Info
Contents
Dapoxetine.
Description
Each film coated tablet contains: Dapoxetine hydrochloride equivalent to Dapoxetine 30 or 60 mg.
Excipients/Inactive Ingredients: Lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl methylcellulose, magnesium stearate, opadry grey 03K575000 and purified water.
Action
Pharmacotherapeutic group: Other urologicals. ATC code: G04BX14.
Pharmacology: Pharmacodynamics: Dapoxetine is a potent selective serotonin reuptake Inhibitor (SSRI) with an IC50 of 1.12 nM, while its major human metabolites, desmethyldapoxetine (IC50 <1.0 nM) and didesmethyldapoxetine (IC50=2.0 nM) are equivalent or less potent (Dapoxetine-N-oxide (IC50=282 nM)).
Human ejaculation is primarily mediated by the sympathetic nervous system. The ejaculatory pathway originates from a spinal reflex centre, mediated by the brain stem, which is influenced initially by a number of nuclei in the brain (medial preoptic and paraventricular nuclei).
The mechanism of action of Dapoxetine in premature ejaculation is presumed to be linked to the inhibition of neuronal reuptake of serotonin and the subsequent potentiation of the neurotransmitter's action at pre and postsynaptic receptors.
Pharmacokinetics: Absorption: Dapoxetine is rapidly absorbed with maximum plasma concentrations (Cmax) occurring approximately 1-2 hours after tablet intake. The absolute bioavailability is 42% (range 15-76%), and dose proportional increases in exposure (AUC and Cmax) are observed between the 30 and 60 mg dose strengths.
Distribution: More than 99% of Dapoxetine is bound in vitro to human serum proteins. The active metabolite desmethyldapoxetine (DED) is 98.5% protein bound. Dapoxetine has a mean steady state volume of distribution of 162 L.
Elimination: The metabolites of Dapoxetine were primarily eliminated in the urine as conjugates. Unchanged active substance was not detected in the urine. Following oral administration, Dapoxetine has an initial (disposition) half-life of approximately 1.5 hours, with plasma levels less than 5% of peak concentrations by 24 hours post-dose, and a terminal half-life of approximately 19 hours.
Indications/Uses
Wonder tablets are indicated for the treatment of premature ejaculation (PE) in adult men aged 18 to 64 years.
Wonder tablets should only be prescribed to patients who meet all the following criteria: An intravaginal ejaculatory latency time (IELT) of less than two minutes; persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the patient's wish; marked personal distress or interpersonal difficulty as a consequence of PE; poor control over ejaculation; a history of premature ejaculation in the majority of intercourse attempts over the prior 6 months.
Wonder tablets should be administered only as on-demand treatment before anticipated sexual activity. It should not be prescribed to delay ejaculation in men who have not been diagnosed with PE.
Dosage/Direction for Use
Adult men (aged 18 to 64 years): The recommended starting dose for all patients is 30 mg, taken as needed approximately 1 to 3 hours prior to sexual activity. Treatment with Wonder should not be initiated with the 60 mg dose.
Wonder tablet is not intended for continuous daily use. It should be taken only when sexual activity is anticipated and must not be taken more frequently than once every 24 hours.
If the individual response to 30 mg is insufficient and the patient has not experienced moderate or severe adverse reactions or prodromal symptoms suggestive of syncope, the dose may be increased to a maximum recommended dose of 60 mg taken as needed approximately 1 to 3 hours prior to sexual activity. The incidence and severity of adverse events is higher with the 60 mg dose.
If the patient experienced orthostatic reactions on the starting dose, no dose escalation to 60 mg should be performed.
Elderly (age 65 years and over): The efficacy and safety of Wonder tablets have not been established in patient's age 65 years and over.
Paediatric population: There is no relevant use of Wonder tablets in this population in the indication of premature ejaculation.
Patients with renal impairment: Caution is advised in patients with mild or moderate renal impairment. Wonder tablet is not recommended for use in patients with severe renal impairment.
Patients with hepatic impairment: Wonder tablet is contraindicated in patients with moderate and severe hepatic impairment (Child-Pugh Class B and C).
METHOD OF ADMINISTRATION: For oral use; Wonder tablet should be swallowed whole to avoid the bitter taste. It is recommended that tablets to be taken with at least one full glass of water and may be taken with or without food.
Precautions to be taken before handling or administering the medicinal product: Before treatment is initiated, see Precautions regarding orthostatic hypotension.
Overdosage
No case of overdose has been reported. In cases of overdose, standard supportive measures should be adopted as required. Due to high protein binding and large volume of distribution of Dapoxetine hydrochloride, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for Wonder tablets are known.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in Excipients/Inactive Ingredients under Description.
Significant pathological cardiac conditions such as: heart failure (NYHA class II-IV); conduction abnormalities such as AV block or sick sinus syndrome; significant ischemic heart disease; significant valvular disease; a history of syncope.
A history of mania or severe depression.
Concomitant treatment with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing treatment with a MAOI. Similarly, a MAOI should not be administered within 7 days after Wonder has been discontinued.
Concomitant treatment with thioridazine or within 14 days of discontinuing treatment with thioridazine. Similarly, thioridazine should not be administered within 7 days after Wonder has been discontinued.
Concomitant treatment with serotonin reuptake inhibitors [selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs)] or other medicinal/herbal products with serotonergic effects [e.g., L-tryptophan, triptans, tramadol, linezolid, lithium, St. John's Wort (Hypericum perforatum)] or within 14 days of discontinuing treatment with these medicinal/herbal products. Similarly, these medicinal/herbal products should not be administered within 7 days after Wonder has been discontinued.
Concomitant treatment of potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, atazanavir etc.
Moderate and severe hepatic impairment.
Special Precautions
General recommendations: Wonder tablet is only indicated in men with premature ejaculation who meet all the criteria listed under Indications, and Pharmacology: Pharmacodynamics under Actions. Wonder tablet should not be prescribed to men who have not been diagnosed with premature ejaculation. Safety has not been established and there are no data on the ejaculation-delaying effects in men without premature ejaculation.
Other forms of sexual dysfunction: Before treatment, subjects with other forms of sexual dysfunction, including erectile dysfunction, should be carefully investigated by physicians. Wonder tablet should not be used in men with erectile dysfunction (ED)who are using PDE5 inhibitors.
Orthostatic hypotension: Before treatment initiation, a careful medical examination including history of orthostatic events should be performed by the physician. In case of a history of documented or suspected orthostatic reaction, treatment with Wonder should be avoided.
The prescriber should also inform the patient not to rise quickly after prolonged lying or sitting.
Suicide/suicidal thoughts: In clinical trials with Dapoxetine for the treatment of premature ejaculation, there was no clear indication of treatment-emergent suicidality in evaluation of possibly suicide-related adverse events evaluated by the Columbia Classification Algorithm of Suicide Assessment (C-CASA), Montgomery-Asberg Depression Rating Scale, or Beck Depression Inventory-II.
Syncope: Patients should be cautioned to avoid situations where injury could result, including driving or operating hazardous machinery, should syncope or its prodromal symptoms such as dizziness or lightheadedness occur.
Possible prodromal symptoms such as nausea, dizziness/lightheadedness, and diaphoresis were reported more frequently among patients treated with Dapoxetine compared to placebo.
Patients with cardiovascular risk factors: Subjects with underlying cardiovascular disease were excluded from Phase 3 clinical trials. The risk of adverse cardiovascular outcomes from syncope (cardiac syncope and syncope from other causes) is increased in patients with underlying structural cardiovascular disease (e.g., documented outflow obstruction, valvular head disease, carotid stenosis and coronary artery disease). There are insufficient data to determine whether this increased risk extends to vasovagal syncope in patients with underlying cardiovascular disease.
Use with recreational drugs: Patients should be advised not to use Wonder tablet in combination with recreational drugs.
Ethanol: Patients should be advised not to use Wonder tablet in combination with alcohol.
Medicinal products with vasodilation properties: Wonder tablet should be prescribed with caution in patients taking medicinal products with vasodilatation properties (such as alpha adrenergic receptor antagonists and nitrates) due to possible reduced orthostatic tolerance.
Moderate CYP3A4 inhibitors: Caution is advised in patients taking moderate CYP3A4 inhibitors and the dose is restricted to 30 mg.
Potent CYP2D6 inhibitors: Caution is advised if increasing the dose to 60 mg in patients taking potent CYP2D6 inhibitors or if increasing the dose to 60 mg in patients known to be of CYP2D6 poor metabolizer genotype, as this may increase exposure levels, which may result in a higher incidence and severity of dose dependent adverse events.
Mania: Wonder tablet should not be used in patients with a history of mania/hypomania or bipolar disorder and should be discontinued in any patient who develops symptoms of these disorders.
Seizure: Due to the potential of SSRIs to lower the seizure threshold, Wonder tablet should be discontinued in any patent who develops seizures and avoided in patients with unstable epilepsy. Patients with controlled epilepsy should be carefully monitored.
Paediatric population: Wonder tablet should not be used in individuals below 18 years of age.
Renal impairment: Wonder tablet is not recommended for use in patents with severe renal impairment and caution is advised in patients with mild or moderate renal impairment.
Withdrawal effects: Abrupt discontinuation of chronically administered SSRIs used to treat chronic depressive disorders has been reported to result in the following symptoms: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia and hypomania.
Effects on ability to drive and use machines: Wonder tablet has minor or moderate influence on the ability to drive and use machines. Dizziness, disturbance in attention, syncope, blurred vision and somnolence has been reported in subjects receiving Wonder tablet in clinical trials. Therefore, patients should be warned to avoid situations where injury could result, including driving or operating hazardous machinery.
Use In Pregnancy & Lactation
Wonder tablet is not indicated for use by women.
Animal studies do not indicate direct or indirect harmful effects with respect to fertility, pregnancy or embryonal/foetal development.
It is not known if either Wonder tablet or its metabolites are excreted in human milk.
Adverse Reactions
The frequencies of adverse reactions are as follows: Very common (>1/10), Common (≥1/100 to < 1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10000 to <1/1000): Psychiatric disorders: Common: Anxiety, agitation, restlessness, insomnia, abnormal dreams, libido decreased.
Uncommon: Depression, depressed mood, euphoric mood, mood altered, nervousness, indifference, apathy, confusional state, disorientation, thinking abnormal, hypervigilance, sleep disorder, initial insomnia, middle insomnia, nightmare, bruxism, loss of libido, anorgasmia.
Nervous system disorders: Very common: Dizziness, headache.
Common: Somnolence, disturbance in attention, tremor, paraesthesia.
Uncommon: Syncope, syncope vasovagal, dizziness postural, akathisia, dysgeusia, hypersomnia, lethargy, sedation, depressed level of consciousness.
Rare: Dizziness exertional, sudden onset of sleep.
Eye disorders: Common: Vision blurred.
Uncommon: Mydriasis, eye pain, visual disturbance.
Ear and labyrinth disorders: Common: Tinnitus.
Uncommon: Vertigo.
Cardiac disorders: Uncommon: Sinus arrest, sinus bradycardia, tachycardia.
Vascular disorders: Common: Flushing.
Uncommon: Hypotension, systolic hypertension, hot flush.
Respiratory, thoracic and mediastinal disorders: Common: Sinus congestion, yawning.
Gastrointestinal disorders: Very common: Nausea.
Common: Diarrhoea, vomiting, constipation, abdominal pain, abdominal pain upper, dyspepsia, flatulence, stomach discomfort, abdominal distension, dry mouth.
Uncommon: Abdominal discomfort, epigastric discomfort.
Rare: Defaecation urgency.
Skin and subcutaneous tissue disorders: Common: Hyperhidrosis.
Uncommon: Pruritis, cold sweat.
Reproductive system and breast disorders: Common: Erectile dysfunction.
Uncommon: Ejaculation failure, male orgasmic disorder, paraesthesia of male genital.
General disorders and administration site conditions: Common: Fatigue, irritability.
Uncommon: Asthenia, feeling hot, feeling jittery, feeling abnormal, feeling drunk.
Investigations: Common: Blood pressure increased. Uncommon: heart rate increased, diastolic blood pressure increased, blood pressure orthostatic increased.
Drug Interactions
Pharmacodynamic Interactions: Potential for interaction with monoamine oxidase inhibitors: Wonder tablet should not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI. Similarly, a MAOI should not be administered within 7 days after Wonder tablet has been discontinued.
Potential for interaction with thioridazine: Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias. Medicinal products such as Wonder tablet that inhibit the CYP2D6 isoenzyme appear to inhibit the metabolism of thioridazine and the resulting elevated levels of thioridazine are expected to augment the prolongation of the QTc interval. Wonder tablet should not be used in combination with thioridazine or within 14 days of discontinuing treatment with thioridazine. Similarly, thioridazine should not be administered within 7 days after Wonder tablet has been discontinued.
Medicinal/herbal products with serotonergic effects: As with other SSRIs, co-administration with serotonergic medicinal/herbal products (including MAOIs, L-tryptophan, triptans, tramadol, linezolid, SSRIs, SNRIs, lithium and St. John's Wort (Hypericum perforatum) preparations) may lead to an incidence of serotonin associated effects. Wonder tablet should not be used in combination with other SSRIs, MAOIs or other serotonergic medicinal/herbal products or within 14 days of discontinuing treatment with these medicinal/herbal products. Similarly, these medicinal/herbal products should not be administered within 7 days after Wonder tablet has been discontinued.
CNS active medicinal products: The use of Wonder tablet in combination with CNS active medicinal products (e.g., antiepileptics, antidepressants, antipsychotics, anxiolytics, and sedative hypnotics) has not been systematically evaluated in patients with premature ejaculation. Consequently, caution is advised if the concomitant administration of Wonder tablet and such medicinal products is required.
Pharmacokinetic Interactions: Effects of co-administered medicinal products on the pharmacokinetics of Wonder tablets: In vitro studies in human liver, kidney and intestinal microsomes indicate Wonder tablet is metabolized primarily by CYP2D6, CYP3A4 and flavin monooxygenase 1 (FMO1). Therefore, inhibitors of these enzymes may reduce Dapoxetine clearance.
CYP3A4 inhibitors: Concomitant use of Wonder tablet and potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir and atazanavir, is contraindicated.
Potent CYP2D6 inhibitors: The Cmax and AUCinf of Wonder tablet (60 mg single dose) increased by 50% and 88%, respectively in the presence of fluoxetine (60 mg/day for 7 days). Considering the contribution of both unbound Dapoxetine and desmethyldapoxetine, the Cmax of the active fraction may be increased by approximately 50% and the AUC of the active fraction may be doubled if taken with potent CYP2D6 inhibitors. These increases in the Cmax and AUC of the active fraction are similar to those expected for CYP2D6 poor metabolizers and may result in a higher incidence and severity of dose dependent adverse events.
PDE5 inhibitors: Wonder tablet should not be used in patients using PDE5 inhibitors due to possible reduced orthostatic tolerance.
Effects of Wonder tablet on the pharmacokinetics of co-administered medicinal products Tamsulosin: The addition of Wonder tablet to tamsulosin did not result in a change in the orthostatic profile and there were no differences in orthostatic effects between tamsulosin combined with either 30 or 60 mg Wonder tablet and tamsulosin alone; however, Wonder tablet should be prescribed with caution in patients who use alpha adrenergic receptor antagonists due to possible reduced orthostatic tolerance.
Warfarin and medicinal products that are known to affect coagulation and/or platelet function: There have been reports of bleeding abnormalities with SSRIs.
Ethanol: Combining alcohol with Wonder tablet may increase alcohol-related effects and may also enhance neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury; therefore, patients should be advised to avoid alcohol while taking Wonder tablet.
Storage
Store below 30°C.
Shelf-Life: 24 months.
ATC Classification
G04BX14 - dapoxetine ; Belongs to the class of other urologicals.
Presentation/Packing
FC tab (grey coloured, round, biconvex, plain on both sides) 30 mg x 1's, 4's. 60 mg x 4's.
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