Extra Super Tadarise (Tadalafil 40 mg + Dapoxetine 60 mg) EU

Product Overview

Extra Super Tadarise is an oral combination tablet containing Tadalafil 40 mg and Dapoxetine 60 mg, manufactured by Sunrise Remedies Pvt. Ltd., an Indian pharmaceutical company with a focus on men’s health and generic medicines. This fixed‑dose combination addresses two of the most common male sexual dysfunctions simultaneously: erectile dysfunction (ED) and premature ejaculation (PE). Tadalafil, a potent and long‑acting phosphodiesterase type 5 (PDE5) inhibitor, restores erectile function by enhancing the nitric oxide–cGMP pathway in the corpus cavernosum. Dapoxetine, a short‑acting selective serotonin reuptake inhibitor (SSRI) with rapid absorption and quick elimination, delays ejaculation by modulating central serotonergic neurotransmission.

The combination is particularly relevant for men in whom ED and PE co‑exist, a frequent clinical scenario. By increasing the reliability of erections and extending intravaginal ejaculatory latency time (IELT), Extra Super Tadarise aims to improve both sexual performance and satisfaction. The 40‑mg Tadalafil component is a dose typically reserved for patients who have responded inadequately to lower doses and require a stronger, sustained effect, while the 60‑mg Dapoxetine component is the standard on‑demand dose for PE.

It is important to note that while Dapoxetine is approved in many countries (including several European and Asian markets) for the on‑demand treatment of PE, fixed‑dose combinations of Tadalafil and Dapoxetine are not approved by the US FDA and are available primarily in markets where such combinations are permitted under local regulations or as “generic‑plus” formulations. Extra Super Tadarise should be used only under appropriate medical supervision.

Chemical Information

Tadalafil

• Chemical Name: (6R,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione
• Molecular Formula: C₂₂H₁₉N₃O₄
• Molecular Weight: 389.40 g/mol
• CAS Number: 171596-29-5
• Chemical Class: PDE5 inhibitor; pyrazinopyridoindole derivative
• Structural Characteristics: Tadalafil is a carboline‑based compound structurally distinct from sildenafil and vardenafil. It contains a tetrahydro‑β‑carboline core with a benzodioxole substituent and a piperazinedione ring. The molecule’s high lipophilicity contributes to its prolonged absorption and extended duration of action.

Dapoxetine

• Chemical Name: (S)-N,N-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine
• Molecular Formula: C₂₁H₂₃NO
• Molecular Weight: 305.41 g/mol (base); 341.46 g/mol (hydrochloride salt)
• CAS Number: 119356-77-3 (Dapoxetine hydrochloride)
• Chemical Class: Short-acting selective serotonin reuptake inhibitor (SSRI); naphthyloxy-amine derivative
• Structural Characteristics: Dapoxetine is structurally related to fluoxetine but possesses a shorter half‑life because of a branched‑chain amine that is rapidly metabolised. Its (S)‑enantiomer is the active form.

Tadalafil is a white crystalline powder practically insoluble in water; Dapoxetine hydrochloride is a white to off‑white powder, freely soluble in water. The combination tablet is formulated for rapid (Dapoxetine) and prolonged (Tadalafil) absorption.

Mechanism of Action

The two active components work through entirely distinct and complementary pharmacological pathways, with no significant pharmacokinetic or pharmacodynamic interaction reported at therapeutic doses.

Tadalafil – PDE5 Inhibition for Erectile Function

Tadalafil selectively inhibits phosphodiesterase type 5, the enzyme responsible for the hydrolysis of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum smooth muscle. Sexual stimulation triggers nitric oxide (NO) release from cavernosal nerves and endothelial cells, activating soluble guanylate cyclase and increasing cGMP synthesis. cGMP relaxes vascular smooth muscle, permitting increased arterial blood flow into the corpora cavernosa and penile erection.

By blocking PDE5, Tadalafil potentiates the NO‑cGMP pathway, enhancing erectile response only when sexual stimulation is present. The key distinguishing feature of Tadalafil among PDE5 inhibitors is its long half‑life (17.5 hours), which provides a therapeutic window of up to 36 hours — clinically termed a “weekend pill” — offering greater spontaneity compared with shorter‑acting agents.

Tadalafil is highly selective for PDE5 over other PDE isoenzymes, though it does exhibit some cross‑reactivity with PDE6 (retinal, causing visual disturbances) and PDE11 (skeletal muscle, causing back pain) at higher doses.

Dapoxetine – Serotonin Transporter Inhibition for Ejaculatory Delay

Dapoxetine is a potent SSRI that inhibits the serotonin transporter (SERT), blocking the reuptake of serotonin (5‑hydroxytryptamine, 5‑HT) into presynaptic neurons, thereby increasing synaptic 5‑HT concentrations. The central control of ejaculation is mediated primarily by serotonergic pathways in the brainstem and spinal cord. Increased 5‑HT tone in these pathways inhibits the ejaculatory reflex, delaying expulsion.

The unique clinical advantage of Dapoxetine is its pharmacokinetic profile: it is rapidly absorbed (Tmax ~1.3 hours) and rapidly eliminated (initial half‑life ~1.5 hours), making it suitable for on‑demand administration 1–3 hours before intercourse. This avoids the need for chronic daily dosing and the associated sexual side effects (e.g., anorgasmia) typical of conventional long‑acting SSRIs.

Synergy

There is no direct pharmacological synergy between Tadalafil and Dapoxetine; they act on entirely separate targets (peripheral vasculature and central nervous system, respectively). Their combination provides functional complementarity by simultaneously improving erectile reliability and ejaculatory control. This dual‑action approach addresses the frequent co‑occurrence of ED and PE, which can constitute a vicious cycle where performance anxiety from ED exacerbates PE, and vice versa.

Pharmacological Effects

In‑Vitro Findings

• Tadalafil inhibits PDE5 with an IC₅₀ of approximately 1–5 nM, demonstrating high selectivity over PDE1–4 and PDE6 (10‑ to 10,000‑fold).
• Dapoxetine inhibits the serotonin transporter with high affinity (Kᵢ ≈ 1 nM) and has minimal affinity for other neurotransmitter receptors, transporters, or ion channels.

Animal Findings

• In conscious rabbit and rat models of penile erection, Tadalafil potentiates erection induced by pelvic nerve stimulation, with effects persisting for hours after oral dosing.
• In male rats, Dapoxetine administered before mating increases the number of intromissions and delays ejaculation in a dose‑dependent manner, consistent with serotonergic modulation of the ejaculatory reflex.

Human Clinical Evidence

Tadalafil: Placebo‑controlled trials in men with ED of varying severity demonstrate that Tadalafil 20–40 mg significantly improves the ability to achieve and maintain erections, with successful intercourse rates of 65–75%. The effect is sustained for up to 36 hours after a single dose.

Dapoxetine: In men with lifelong or acquired PE, Dapoxetine 60 mg on‑demand increases the geometric mean IELT from approximately 0.9 minutes (baseline) to 3.3–3.8 minutes, with 30–40% of patients achieving an IELT ≥2 minutes. Patient‑reported control over ejaculation and sexual satisfaction improved significantly.

Combination: Although formal large‑scale randomised trials of the fixed‑dose combination are limited, observational studies and meta‑analyses of combination therapy in men with both ED and PE report improved erectile function scores (IIEF‑5), longer IELT, and greater overall sexual satisfaction compared with either agent alone or placebo. The combination is generally well tolerated, with adverse events consistent with the known profiles of each component.

Dosage

Extra Super Tadarise contains Tadalafil 40 mg and Dapoxetine 60 mg in a single tablet. It is intended for on‑demand, as‑needed use.Export

Parameter	Recommendation
Dose	One tablet (40 mg Tadalafil / 60 mg Dapoxetine)
Timing	Taken 1–3 hours before anticipated sexual activity
Maximum frequency	Once in 24 hours; not for daily use
Food interaction	Tadalafil absorption is not affected by food; Dapoxetine absorption may be slightly delayed by a heavy fatty meal but is not clinically significant.

Important cautions:

• The 40 mg Tadalafil dose is higher than the standard starting dose (10 mg) and is intended for patients who have not responded adequately to lower doses and who have been assessed for cardiovascular risk.
• Alcohol consumption should be minimised or avoided; Dapoxetine may potentiate sedation, and both alcohol and Tadalafil can cause vasodilation and hypotension.
• Grapefruit or grapefruit juice should be avoided as it may increase Tadalafil plasma concentrations and the risk of adverse effects.
• This product is not indicated for continuous daily use; Tadalafil daily dosing for ED (2.5–5 mg/day) is not replicated by intermittent high‑dose use.

Pharmacokinetics

Tadalafil

• Absorption: Rapidly absorbed after oral administration; Tmax 0.5–6 hours (median 2 hours). Absolute bioavailability has not been determined, but systemic exposure is dose‑proportional from 2.5–40 mg. Food does not affect absorption.
• Distribution: Volume of distribution ~63 L, indicating extensive tissue distribution. Approximately 94% bound to plasma proteins.
• Metabolism: Primarily hepatic, via CYP3A4 to an inactive catechol metabolite, which is further glucuronidated.
• Half‑life: 17.5 hours in healthy men — the longest among PDE5 inhibitors. Clearance: 2.5 L/h.
• Elimination: Excreted mainly as metabolites in faeces (~61%) and urine (~36%).

Dapoxetine

• Absorption: Rapidly absorbed; Tmax ~1.3 hours (fasting). High‑fat meal slightly delays Tmax and reduces Cmax by 10% but does not meaningfully alter AUC. Bioavailability ~42% because of first‑pass metabolism.
• Distribution: Volume of distribution ~2 L/kg. More than 99% protein‑bound.
• Metabolism: Extensively metabolised by CYP2D6, CYP3A4, and flavin‑containing monooxygenase 1 (FMO1) to inactive metabolites. Genetic CYP2D6 poor metabolisers may have 2‑ to 3‑fold higher plasma concentrations.
• Half‑life: Initial half‑life ~1.5 hours, terminal half‑life ~20 hours (minor). Rapid clearance allows on‑demand use without accumulation.
• Elimination: Metabolites excreted primarily in urine.

Absence of Significant Pharmacokinetic Interaction

Formal interaction studies have not shown clinically significant mutual effects when Tadalafil and Dapoxetine are co‑administered. Tadalafil does not meaningfully alter Dapoxetine’s CYP2D6 metabolism, and Dapoxetine does not affect Tadalafil’s CYP3A4 clearance at therapeutic concentrations.

Side Effects and Safety

The adverse effect profile of Extra Super Tadarise reflects the known profiles of each component.

Tadalafil‑Related

• Common: Headache (10–15%), dyspepsia, back pain, myalgia (typically 12–24 hours post‑dose, resolving within 48 hours), nasal congestion, facial flushing. Back pain and myalgia are more specific to Tadalafil and are related to PDE11 inhibition in skeletal muscle.
• Serious: Priapism (painful erection lasting >4 hours) is a medical emergency and requires immediate intervention. Sudden vision loss (non‑arteritic anterior ischaemic optic neuropathy, NAION) and sudden hearing loss have been reported rarely with PDE5 inhibitors; causality is uncertain but patients should be advised to discontinue and seek medical attention.

Dapoxetine‑Related

• Common: Nausea (10–15%, often mild and transient), dizziness, headache, diarrhoea, somnolence.
• Serious: Syncope and orthostatic hypotension (especially with concomitant alcohol or vasodilators); seizures (rare); serotonin syndrome (with concomitant serotonergic drugs). Mood changes, including suicidal ideation, have been reported with SSRIs; although Dapoxetine is short‑acting, patients with a history of psychiatric illness should be assessed.

Contraindications

• Concomitant use of nitrates in any form (e.g., nitroglycerin, isosorbide mononitrate) or nitric oxide donors (e.g., amyl nitrite “poppers”) is absolutely contraindicated with Tadalafil because of the risk of severe, potentially fatal hypotension.
• Concomitant use of monoamine oxidase inhibitors (MAOIs) or other serotonergic drugs (e.g., SSRIs, SNRIs, triptans, tramadol, St John’s Wort) with Dapoxetine increases the risk of serotonin syndrome.
• Severe hepatic impairment (Child‑Pugh C) or end‑stage renal disease requiring dialysis.
• Patients with significant cardiovascular disease for whom sexual activity is inadvisable (e.g., unstable angina, recent myocardial infarction, severe aortic stenosis, uncontrolled arrhythmias, severe hypotension or uncontrolled hypertension).
• Known hypersensitivity to any component.

Dependence, Tolerance and Withdrawal

Neither component has recognised abuse potential or dependence liability. Tolerance does not develop to the therapeutic effects of Tadalafil with intermittent use. Dapoxetine’s short acting nature and on‑demand mode of use minimise the risk of withdrawal phenomena; abrupt discontinuation after prolonged daily use (which is not the indication) could theoretically produce SSRI‑withdrawal symptoms, but this is not relevant for the intended intermittent use of this combination.

Harm Reduction and Safe Use

• Nitrates: Absolutely contraindicated. This must be communicated clearly to patients, including recreational use of amyl nitrite.
• Alcohol: Excessive alcohol consumption should be avoided; it can impair erectile function and may exacerbate Dapoxetine‑related dizziness and hypotension.
• Grapefruit: Avoid grapefruit juice, which can increase Tadalafil exposure.
• Priapism: Seek urgent medical attention for an erection lasting >4 hours.
• Driving and operating machinery: Dapoxetine may cause dizziness or somnolence. Patients should assess their response before driving.
• Drug interactions: Inform the prescriber of all medications, particularly nitrates, alpha‑blockers, antihypertensives, other PDE5 inhibitors, serotonergic drugs, and strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) which can increase Tadalafil levels.
• Labelling: Not for women or children. Store below 30°C, protected from moisture. Keep out of reach of children.
• Disposal: Follow local pharmaceutical disposal guidelines.

Legal and Regulatory Status

• India: Extra Super Tadarise is manufactured by Sunrise Remedies for markets where combination products for ED/PE are registered. In India, the legal pathway for such fixed‑dose combinations may require specific approval. Prescribers and patients should verify current regulatory status and ensure the product is obtained through legal, regulated supply chains. It is classified as a prescription (Schedule H) medication.
• Global: Neither the fixed‑dose combination nor Dapoxetine 60 mg with Tadalafil 40 mg as a combined tablet is approved by the US FDA or the European Medicines Agency at the time of writing, though individual components are approved separately in many jurisdictions. Availability abroad varies, often through online channels; patients should be cautious of unregulated sources.

Research Applications

• Sexual medicine: The combination continues to be studied for the optimal management of co‑occurring ED and PE, including dose‑ranging, long‑term safety, and quality‑of‑life outcomes.
• Pharmacology: Investigation of PDE5 inhibitor and SSRI combination effects on peripheral and central pathways regulating erection and ejaculation.
• PK/PD modelling: Studying the optimal time window and dose ratios for on‑demand dual‑mechanism therapy.

Conclusion

Extra Super Tadarise by Sunrise Remedies combines the long‑acting PDE5 inhibitor Tadalafil (40 mg) with the short‑acting SSRI Dapoxetine (60 mg) to provide an on‑demand, dual‑action treatment for men with co‑existing erectile dysfunction and premature ejaculation. Tadalafil enhances erectile response via the NO‑cGMP pathway for up to 36 hours; Dapoxetine rapidly increases central serotonin activity to delay ejaculation within 1–3 hours of ingestion. The combination addresses the frequent clinical overlap of ED and PE through complementary mechanisms. While the individual components are well‑established, the fixed‑dose combination per se lacks approval from major Western regulators, and its use should be supervised by a qualified physician, with strict avoidance of nitrates and careful cardiovascular and psychiatric assessment. It is a prescription product, not for daily use, and not intended for women or children.