Maynmar Product

Wonder Tablets

Wonder Tablets

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:

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; and
 Persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the patient wishes; and
 Marked personal distress or interpersonal difficulty as a consequence of PE; and
 Poor control over ejaculation; and
 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.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:

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.

UNDESIRABLE EFFECTS
Tabulated list of adverse reactions

Table 1: Frequency of Adverse Reactions (MedDRA)

System Organ Class

Very common
(> 1/10)

Common
(≥ 1/100 to < 1/10)

Uncommon
(≥ 1/1000 to < 1/100)

Rare
(≥ 1/10000 to < 1/1000)

Psychiatric disorders

 

Anxiety, Agitation, Restlessness, Insomnia, Abnormal dreams, Libido decreased

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

Dizziness, Headache

Somnolence, Disturbance in attention, Tremor, Paraesthesia

Syncope, Syncope vasovagal, Dizziness postural, Akathisia, Dysgeusia, Hypersomnia, Lethargy, Sedation, Depressed level of consciousness

Dizziness exertional, Sudden onset of sleep

Eye disorders

 

Vision blurred

Mydriasis, Eye pain, Visual disturbance

 

Ear and labyrinth disorders

 

Tinnitus

Vertigo

 

Cardiac disorders

 

 

Sinus arrest, Sinus bradycardia, Tachycardia

 

Vascular disorders

 

Flushing

Hypotension, Systolic hypertension, Hot flush

 

Respiratory, thoracic and mediastinal disorders

 

Sinus congestion, Yawning

 

 

Gastrointestinal disorders

Nausea

Diarrhoea, Vomiting, Constipation, Abdominal pain, Abdominal pain upper, Dyspepsia, Flatulence, Stomach discomfort, Abdominal distension, Dry mouth

Abdominal discomfort, Epigastric discomfort

 

 

Defaecation urgency

Skin and subcutaneous tissue disorders

 

Hyperhidrosis

Pruritis, Cold sweat

 

Reproductive system and breast disorders

 

Erectile dysfunction

Ejaculation failure, Male orgasmic disorder, Paraesthesia of genital male

 

General disorders and administration site conditions

 

Fatigue, Irritability

Asthenia, Feeling hot, Feeling jittery, Feeling abnormal, Feeling drunk

 

Investigations

 

Blood pressure increased

Heart rate increased, Blood pressure diastolic increased, Blood pressure orthostatic increased

 


3. What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

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.

What to do if you accidentally take too much (overdose) of the medicine?

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.

Is it safe in pregnancy and breast-feeding?

Wonder tablet is not indicated for use by women.

Storage Conditions:

Store below 30°C.
Keep all medicines out of reach of children.

Drug Description

Drug description

General physico-chemical properties
Grey coloured, round, biconvex film coated tablets plain on both sides.

Composition
Each Film coated tablet contains 
Dapoxetine hydrochloride equivalent to Dapoxetine………………. 30 mg/ 60 mg

Excipients:Lactose Monohydrate, Microcrystalline Cellulose, Croscarmellose Sodium, Hydroxypropyl Methylcellulose, Magnesium Stearate, Opadry Grey 03K575000 and Purified Water.

Indications and dosage.

INDICATIONS:
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; and
 Persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the patient wishes; and
 Marked personal distress or interpersonal difficulty as a consequence of PE; and
 Poor control over ejaculation; and
 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 AND METHOD OF ADMINISTRATION
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 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 section “Special warnings and precautions” regarding orthostatic hypotension.

Side effects and drug interactions.

  Adverse reactions:
Tabulated list of adverse reactions

Table 1: Frequency of Adverse Reactions (MedDRA)

System Organ Class

Very common
(> 1/10)

Common
(≥ 1/100 to < 1/10)

Uncommon
(≥ 1/1000 to < 1/100)

Rare
(≥ 1/10000 to < 1/1000)

Psychiatric disorders

 

Anxiety, Agitation, Restlessness, Insomnia, Abnormal dreams, Libido decreased

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

Dizziness, Headache

Somnolence, Disturbance in attention, Tremor, Paraesthesia

Syncope, Syncope vasovagal, Dizziness postural, Akathisia, Dysgeusia, Hypersomnia, Lethargy, Sedation, Depressed level of consciousness

Dizziness exertional, Sudden onset of sleep

Eye disorders

 

Vision blurred

Mydriasis, Eye pain, Visual disturbance

 

Ear and labyrinth disorders

 

Tinnitus

Vertigo

 

Cardiac disorders

 

 

Sinus arrest, Sinus bradycardia, Tachycardia

 

Vascular disorders

 

Flushing

Hypotension, Systolic hypertension, Hot flush

 

Respiratory, thoracic and mediastinal disorders

 

Sinus congestion, Yawning

 

 

Gastrointestinal disorders

Nausea

Diarrhoea, Vomiting, Constipation, Abdominal pain, Abdominal pain upper, Dyspepsia, Flatulence, Stomach discomfort, Abdominal distension, Dry mouth

Abdominal discomfort, Epigastric discomfort

 

 

Defaecation urgency

Skin and subcutaneous tissue disorders

 

Hyperhidrosis

Pruritis, Cold sweat

 

Reproductive system and breast disorders

 

Erectile dysfunction

Ejaculation failure, Male orgasmic disorder, Paraesthesia of genital male

 

General disorders and administration site conditions

 

Fatigue, Irritability

Asthenia, Feeling hot, Feeling jittery, Feeling abnormal, Feeling drunk

 

Investigations

 

Blood pressure increased

Heart rate increased, Blood pressure diastolic 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 an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, an 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.

Warnings and precautions

General recommendations
Wonder tablet is only indicated in men with Premature Ejaculation who meet all the criteria listed in sections of therapeutic indications and pharmacodynamics. 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. An orthostatic test should be performed before initiating therapy (blood pressure and pulse rate, supine and standing). 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 Algorhythm 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.
Possibly 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 heart 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 vasodilatation 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 patient 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 patients 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.


Overdosage and Contraindications

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 above.
  • 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 an MAOI. Similarly, an 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, nefazadone, nelfinavir, atazanavir, etc.
  • Moderate and severe hepatic impairment.
  • Clinical pharmacology.

    PHARMACOLOGIC PROPERTIES
    Pharmacodynamic Properties

    Pharmacotherapeutic Group: Other Urologicals

    ATC code: G04BX14

    Mechanism of action
    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. The terminal half−life of DED is approximately 19 hours.

    STORAGE CONDITION
    Store below 30°C.
    Keep all medicines out of reach of children.

    DOSAGE FORM AND PACKING AVAILABLE
    Alu/Alu blister of 1 or 4 tablets, each blister in a carton.

    NAME AND ADDRESS OF MANUFACTURER
    Kusum Healthcare Pvt. Ltd.
    SP 289 (A), RIICO, Indl. Area,
    Chopanki, Bhiwadi (Rajasthan), India

    CERTIFICATES

    KEEP IN TOUCH

    Kusum Healthcare
    D-158A, OKHLA,INDUSTRIAL AREA,
    PHASE-I, NEW DELHI,
    Pin 110020
    INDIA
    Tel: 011-41005147, 011-40514919
    Fax: +91-11-40527575