Medication Combo for Sexual Health
A drug duo, commonly known as Vardenafil & Dapoxetine, serves as a potent remedy for male sexual health issues. Dapoxetine, alternatively named Priligy, acts to combat premature ejaculation (PE) by disrupting serotonin transmission and thus prolonging the time to ejaculation. On the other hand, Vardenafil is prescribed for erectile dysfunction (ED) by enhancing penile blood circulation during arousal, aiding in achieving and maintaining an erection. This dynamic combination tackles two common male sexual concerns effectively and efficiently.
The way it works:
Vardenafil blocks the activity of a specific enzyme called phosphodiesterase 5 (PDE5), which is involved in breaking down a molecule called cGMP in the erectile tissue surrounding the male reproductive organ. The process of achieving an erection during sexual arousal is linked to an enhanced blood flow to the penis due to the relaxation of blood vessels and muscle tissue in the erectile tissue. This relaxation is triggered by the release of nitric oxide (NO) from nerve endings and cells lining the blood vessels, leading to the production of cGMP in the muscle cells. The presence of cGMP causes the smooth muscle to function improperly and results in increased blood flow. By blocking the action of phosphodiesterase type 5 (PDE5), vardenafil improves erectile function by boosting the levels of cGMP.
Dapoxetine, a highly effective medication, acts by selectively inhibiting serotonin reuptake in the brain, demonstrating remarkable potency with an IC50 of 1.12 nm.
Medication Combo for Sexual Health
A drug duo, commonly known as Vardenafil & Dapoxetine, serves as a potent remedy for male sexual health issues. Dapoxetine, alternatively named Priligy, acts to combat premature ejaculation (PE) by disrupting serotonin transmission and thus prolonging the time to ejaculation. On the other hand, Vardenafil is prescribed for erectile dysfunction (ED) by enhancing penile blood circulation during arousal, aiding in achieving and maintaining an erection. This dynamic combination tackles two common male sexual concerns effectively and efficiently.
The way it works:
Vardenafil blocks the activity of a specific enzyme called phosphodiesterase 5 (PDE5), which is involved in breaking down a molecule called cGMP in the erectile tissue surrounding the male reproductive organ. The process of achieving an erection during sexual arousal is linked to an enhanced blood flow to the penis due to the relaxation of blood vessels and muscle tissue in the erectile tissue. This relaxation is triggered by the release of nitric oxide (NO) from nerve endings and cells lining the blood vessels, leading to the production of cGMP in the muscle cells. The presence of cGMP causes the smooth muscle to function improperly and results in increased blood flow. By blocking the action of phosphodiesterase type 5 (PDE5), vardenafil improves erectile function by boosting the levels of cGMP.
Dapoxetine, a highly effective medication, acts by selectively inhibiting serotonin reuptake in the brain, demonstrating remarkable potency with an IC50 of 1.12 nm.
Pharmacokinetics:
The absorption of vardenafil in tablet form is a rapid process, leading to peak plasma concentrations being observed within 15 minutes of oral intake in some individuals. However, in 90% of cases, peak plasma levels are reached between 30 to 120 minutes (typically around 60 minutes) after oral administration on an empty stomach. The average oral bioavailability of vardenafil is 15%. The oral dosage of vardenafil is adjusted in proportion to achieve the recommended dose range (5 – 20 mg) for AUC and Cmax.
If vardenafil tablets are consumed alongside a high-fat meal (with 57% fat content), the rate of absorption slows down, resulting in a delay of approximately 1 hour to reach peak levels and an average reduction of 20% in Cmax.
Vardenafil does not experience any changes in AUC levels. Even after consuming a meal high in fat content by 30%, the absorption rate and extent of vardenafil (including Tmax, Cimax, and AUC) remain consistent with those observed when taken on an empty stomach. With regards to distribution, the steady-state volume of distribution for Vardenfil is 208 L, indicating its wide distribution in various tissues. Both vardenafil and its primary circulating metabolite (M1) exhibit high levels of binding to plasma proteins, with approximately 95% of vardenafil or M1 being bound. The protein binding of vardenafil and M1 occurs independently of the total drug concentrations.
Quantifying vardenafil levels in the seminal fluid of healthy volunteers 1.5 hours post-administration revealed minimal presence of just 0.00012% of the initial dose. The primary route of vardenafil metabolism occurs in the liver, predominantly through cytochrome P450 (CYP) enzyme 3A4, with some involvement of CYP3A5 and CYP2C isoforms. Metabolism of vardenafil yields the major circulating metabolite M1 in humans, which undergoes further elimination with a plasma half-life of around 4 hours.
Certain segments of M1 are found as glucuronide in the bloodstream. M1's metabolite showcases a phosphodiesterase preference akin to vardenafil, demonstrating about 28% potency for phosphodiesterase type 5 compared to vodafil, thereby contributing to efficacy by roughly 7%.
Disposal: Vardenafil undergoes a total body clearance of 56 L/h, resulting in a half-life of roughly 4–5 hours. Following oral intake, vardenafil is primarily expelled through feces as metabolites (constituting around 91–95% of the administered dosage) and to a lesser extent through urine (approximately 2–6% of the administered dosage).
Mechanism of action of the drug:
Dapoxetine is a serotonin reuptake inhibitor. Dapoxetine is a short-acting SSRI drug that is currently being considered for approval by the Food and Drug Administration (FDA) for the treatment of premature ejaculation in men, which would be the first drug approved for such treatment. Although two clinical studies were completed in 2006, experts expect it to be approved by the FDA soon because SSRIs cause unwanted side effects after long-term use, such as mental problems, skin reactions, weight gain and decreased sex drive.
Nausea can bring about discomfort in the form of headaches, stomach issues, and fatigue, leading to the conclusion that the downsides of premature ejaculation don't match up to the advantages of the medication. In contrast to the extended time it takes for SSRIs designed for treating depression to become effective (typically 2 weeks or more), dapoxetine boasts a distinctive pharmacokinetic profile, characterized by a rapidly achieved peak serum concentration (approximately within 1 hour) and swift elimination (half-life of 1-2 hours).
Preventative Measures:
Vardenafil has the potential to trigger a heart rhythm disorder known as prolonged QT, which, albeit rarely, can result in severe (and even fatal) accelerated/irregular heart palpitations, along with other symptoms like intense dizziness and fainting that necessitate immediate medical intervention.
In case of existing medical conditions or potential long QT interval, the combination of various medications could elevate the risk of prolonged QT. Prior to vardenafil usage, it is crucial to disclose to your healthcare provider or pharmacist all the medications you are currently on and any of the following conditions: clear indications of heart issues (heart failure, bradycardia, EKG Prolonged QT), familial history of heart conditions (QT), long duration on EKG, sudden cardiac arrest. Insufficient levels of potassium or magnesium in your bloodstream may further raise the chances of prolonged QT. This risk might escalate if you are taking specific medications (like diuretics / “water pills”) or experiencing situations such as excessive sweating, diarrhea, or vomiting. Consult your doctor for a secure vardenafil usage.
Uncommonly, there may be instances of sudden hearing impairment or complete loss coupled with sensations of ringing and vertigo in the ears. Should these symptoms manifest, discontinue the usage of wardenfil without delay and promptly seek medical intervention. In the unlikely scenario of experiencing intense or protracted discomfort persisting for 4 hours or more, cease the administration of this medication immediately and seek urgent medical assistance to avert potential enduring complications. Should any grave adverse reactions arise, do not hesitate to seek immediate medical attention, including but not limited to: swift or irregular heartbeat, convulsions, transient amnesia. While exceedingly rare, a severe allergic response to this medication may occur. If indications of a severe allergic reaction become apparent, promptly seek medical assistance, encompassing symptoms such as: rash, pruritus, or edema (especially of the visage, tongue, or throat), severe vertigo, or breathlessness.
Dosage:
Usual Adult Dose for Erectile Dysfunction:
Patients on stable alpha-blocker therapy:
Overdose:
In a single-dose study, doses including 80 mg and vardenafil per day were tolerated without the occurrence of serious adverse reactions.
There have been cases of severe back pain with high doses of vardenafil and exceeding the recommended dosage regimen (40 mg tablets twice a day). It is not associated with any muscle or neurological toxicity.
If you happen to take too much of this medication, make sure to follow the standard supportive procedures as necessary. It's unlikely that kidney dialysis will speed up the removal process since vardenafil attaches strongly to blood proteins and doesn't get significantly flushed out through urine.
Cautions:
Certain medications might lead to undesirable or risky outcomes when combined with vardenafil. Inform your healthcare provider about all your prescribed and over-the-counter drugs, particularly Riociguat (adempas).
Avoid using vardenafil if you're already taking nitrate medications for heart conditions or chest pain, such as nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, and certain recreational substances like "poppers". Combining vardenafil with nitrate meds could result in a sudden and severe drop in blood pressure.
Interaction of medicinal substances:
The combination of Vardenafil and certain groups of pharmaceuticals should be strictly avoided for individuals who are prescribed nitrate-based drugs, as the joint intake of these compounds may result in a dangerous decrease in blood pressure that could potentially be life-threatening. Furthermore, the administration of Vardenafil has been known to significantly lengthen the QT interval. This implies that it should not be consumed alongside other medications that have an impact on the QT interval, such as amiodarone.
Adverse effects:
The side effects associated with Vardenafil are mainly in line with those of similar pharmaceuticals that are classified as PDE5 inhibitors. Some common negative reactions specific to Vardenafil may include symptoms like nausea, with other related adverse effects being abdominal discomfort, spinal discomfort, heightened sensitivity, unusual visual disturbances, ocular pain, swelling of facial tissues, low blood pressure, palpitations, rapid heart rate, joint pain, muscle pain, skin rash, itchiness, and delayed responses.
Potentially serious and uncommon adverse reactions linked to vardenafil include cardiac incidents. Additionally, in sporadic instances, the consumption of vardenafil could trigger priapism, an excruciating emergency situation that may result in erectile dysfunction when incapable. The US Food and Drug Administration (FDA) declared on 18 October 2007 that a notification concerning potential hearing loss would be integrated into the medication label of vardenafil and other PDE5 inhibitors.
Maternity:
No research has been conducted on the administration of this medication in expecting females.
Fertility:
Vardenafil is not intended for usage by females. There have been no examinations on vardenafil in expecting females. There is an absence of reproductive data accessible.