For the use only of a registered medical practitioner, Hospital or Laboratory
Dapoxetine and Tadalafil Tablets
Each film coated tablet contains:
Dapoxetine Hydrochloride IP equivalent to Dapoxetine 60 mg
Tadalafil 20 mg
Colours: Titanium Dioxide BP, Quinoline Yellow Aluminum Lake
Tadalafil: (6R-trans)-6-(1,3-benzodioxol-5-yl)- 2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino [1′, 2′:1,6] pyrido[3,4-b]indole-1,4-dione
Dapoxetine: (+)-(S)-N, N-dimethyl-(‹)-[2-(1-naphthalenyloxy) ethyl]- benzenemethanamine hydrochloride
Tadalafil: Selective phosphodiesterase type-5 (PDE5) inhibitor
Dapoxetine: Selective serotonin reuptake inhibitor (SSRI)
DESCRIPTION: EXILAR MAX contains Tadalafil 20 mg and Dapoxetine hydrochloride 60 mg.
Tadalafil: Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation.
Dapoxetine: 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 post-synaptic receptors. 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).
Tadalafil: The maximum plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). The rate and extent of absorption of tadalafil are not influenced by food.
At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins.
Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. The major circulating metabolite is the methylcatechol glucuronide.
The mean terminal half-life is 17.5 hours and excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
Dapoxetine: 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%). Ingestion of a high fat meal modestly reduced the Cmax (by 10%) and modestly increased the AUC (by 12%) of dapoxetine and slightly delayed the time for dapoxetine to reach peak concentrations; however, the extent of absorption was not affected by consumption of a high fat meal.
Greater than 99% of dapoxetine is bound in vitro to human proteins. The active metabolite desmethyldapoxetine is 98.5% protein bound.
Dapoxetine was extensively metabolized to multiple metabolites primarily through the following biotransformational pathways: N-oxidation, N-demethylation, naphthyl hydroxylation, glucuronidation and sulfation.
The terminal half-life is approximately 19 hours following oral administration.
EXILAR MAX is indicated for the treatment of Erectile Dysfunction (ED) and Premature Ejaculation (PE) in men.
DOSAGE AND ADMINISTRATION
Take 1 tablet of EXILAR MAX before 1-3 hours of sexual activity. The maximum recommended dosing frequency is once daily.
EXILAR MAX is contraindicated in patients with known hypersensitivity, moderate and severe hepatic impairment, significant pathological cardiac conditions (such as heart failure (NYHA class II-IV), conduction abnormalities (second- or third-degree AV block or sick sinus syndrome), ischemic heart disease or valvular disease.
WARNINGS AND PRECAUTIONS
EXILAR MAX is prescribed for adult males only (18 years and older).
EXILAR MAX is indicated in men with premature ejaculation (PE) and erectile dysfunction (ED).
EXILAR MAX must not be used by anyone taking nitrate medication or alcohol.
Use of EXILAR MAX is not recommended for people with a history of cardiovascular disease, eye problems, renal impairment, hepatic impairment and urological conditions.
Consult a medical professional immediately if you experience erections lasting longer than 4 hours and priapism (prolonged erections greater than 6 hours).
Patients should be advised not to use EXILAR MAX in combination with recreational drugs such as ketamine, methylenedioxy- methamphetamine (MDMA) and lysergic acid diethylamide (LSD) may lead to potentially serious reactions if combined with EXILAR MAX.
The occurrence of syncope and possibly prodromal symptoms appears dose dependent as demonstrated by higher incidence among patients treated with doses of Dapoxetine higher than 60 mg, the recommended maximum daily dose.
EXILAR MAX should be prescribed with caution in patients taking medicinal products with vasodilatation properties (such as alpha adrenergic receptor antagonists, nitrates, PDE5 inhibitors) due to possible reduced orthostatic tolerance.
EXILAR MAX 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.
EXILAR MAX should be discontinued in any patient who develops seizures and avoided in patients with unstable epilepsy. Patients with controlled epilepsy should be carefully monitored.
EXILAR MAX is contraindicated for concomitant treatment with monoamine oxidase inhibitors (MAOIs), thioridazine, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), L-tryptophan, triptans, tramadol, linezolid, lithium, St. John’s Wort (Hypericum perforatum), nitrates, alpha-blockers, antihypertensive (amlodipine, angiotensin II receptor blocker, bendrofluazide, enalapril, and metoprolol), antacids, H2 antagonists (nizatidine), cytochrome P450 inducers (rifampin), aspirin, P-glycoprotein (digoxin), theophylline, warfarin, midazolam and lovastatin.
EXILAR MAX is contraindicated for concomitant treatment with potent cytochrome P450 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, atazanavir, erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem, desmipramine and midazolam.
USE IN PREGNANCY AND LACTATION
EXILAR MAX is not safe for use during pregnancy and lactation.
According to reported studies, most common adverse drug reactions are headache, dizziness, nausea, diarrhea, insomnia, fatigue, dyspepsia, back pain, myalgia, nasal congestion, flushing, and pain in limb.
Other reported adverse reactions include increased blood pressure, tremor, paraesthesia, disturbance in attention, blurred vision, tinnitus, sinus congestion, yawning, abdominal pain, dry mouth, vomiting, , flatulence, hyperhidrosis, irritability, erectile dysfunction, anxiety, nervousness, decreased libido, depression, apathy and abnormal dreams.
In general, symptoms of overdose with SSRIs include serotonin-mediated adverse reactions such as somnolence, gastrointestinal disturbances such as nausea and vomiting, tachycardia, tremor, agitation and dizziness.
In cases of overdose, standard supportive measures should be adopted as required. Due to high protein binding and large volume of distribution, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.
PRESENTATION : Blister of 4 Tablets
STORAGE: Store in a cool and dry place below 30°C.
Protect from light and moisture.
Keep out of reach of children.
LAST UPDATE: October 2014.