Vardenafil
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Phosphodiesterase-5 (PDE5) inhibitors, Therapy Class:
Impotence agents, Approved Countries
The United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Spain, Japan, India, Brazil and Mexico.
Vardenafil is an impotence agent belonging to the pharmacological class of Phosphodiesterase-5 Enzyme Inhibitors (PDE5).
The FDA approves Vardenafil for treating erectile dysfunction (the inability to keep an erection firm enough for sexual activity) in men.
Vardenafil has a 15% bioavailability and peaks in 0.5-2 hours, although high-fat meals inhibit this rapid absorption. The drug circulates widely, is metabolized by the liver, and is mainly excreted in urine and faeces.
The most common side effects of Vardenafil include flushing, headache, dizziness, blurred vision, muscle pain, stomach upset, nasal congestion, and rash.
Vardenafil is available in the form of oral tablets.
The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Spain, Japan, India, Brazil and Mexico.
Vardenafil is an impotence agent belonging to the pharmacological class of Phosphodiesterase-5 Enzyme Inhibitors (PDE5).
When cyclic guanosine monophosphate (GMP) is found in the corpus cavernosum, which is the area surrounding the penis, phosphodiesterase type 5 (PDE5), which is specialized for cyclic GMP, is inhibited by Vardenafil. The increased penile blood flow that results from the relaxing of the corpus cavernosal smooth muscle and penile arteries during sexual stimulation is what causes a penile erection. Nerve terminals and endothelial cells emit nitric oxide (NO), which triggers smooth muscle cells to produce cyclic GMP. NO mediates this reaction. In the corpus cavernosum, cyclic GMP results in relaxed, smooth muscles and enhanced blood flow. PDE5 is the most prevalent PDE in the human corpus cavernosum. PDE5 regulates the tissue concentration of cyclic GMP by controlling the synthesis and degradation rates. PDEs break down cyclic GMP. Thus, by raising the level of cyclic GMP, Vardenafil's inhibition of PDE5 improves erectile function.
The data duration of Vardenafil action is about four to six hours after administration.
The onset of Vardenafil action typically occurs within approximately 30 to 60 minutes.
The Data of Cmax of Vardenafil occurs at approximately one hour post-administration.
The data of Tmax of Vardenafil ranges between 30 minutes and 2 hours after oral administration.
Vardenafil is available in the form of oral tablets.
Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.
As the physician recommends, take the medication orally once daily; it can be taken with or without food as directed.
Vardenafil can be used for the following health conditions:
- Erectile Dysfunction: Treats and manages erectile dysfunction in adult males.
- Off-label Use: Occasionally employed for pulmonary hypertension and potential management of premature ejaculation (lacking official approval for this use)
In Erectile dysfunction
Vardenafil efficiently treats erectile dysfunction only when used in response to sexual excitement by prolonging erections by suppressing specific natural body chemicals. Vardenafil helps to achieve an erection by relaxing the blood vessels in the penis, which allows for higher blood flow during sexual stimulation. Giving it at least 30 minutes before engaging in sexual activity is necessary for its effectiveness. It is not recommended to consume it with nitrates, so proceed with caution.
Vardenafil is commonly indicated for the treatment of erectile dysfunction in adult males. It also helps to improve overall sexual satisfaction, enhance sexual function, and help achieve and sustain erections that are sufficient for satisfying sexual performance.
Orally: Vardenafil is typically taken orally as a single-dose tablet, and it is advised to be taken once daily, which is the maximum dosing frequency with or without food. The recommended starting dose is usually 10 milligrams, taken orally about 30-60 minutes before anticipated sexual activity. For the disintegrating tablet, place it on the tongue where it dissolves; do not swallow and take without liquid.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Tablet (film coated): 2.5mg, 5mg, 10mg, 20mg.
Vardenafil is available in the form of oral tablets.
Dose Adjustment in Adult Patients:
Erectile Dysfunction
10 mg PO approximately 1 hour before sexual activity; based on effectiveness and tolerance, this dose may be increased upto 20 mg or decreased to 5 mg; no more than one dose per day.
Dosage Modifications
Nitrates and guanylate cyclase (GC) stimulators given concurrently: Not recommended.
When co-administering CYP3A4 inhibitors
Tablet
200 mg of ketoconazole or 200 mg of itraconazole each day: The maximum daily dosage of Vardenafil is 5 mg.
Vardenafil dosage: recommended not to exceed 2.5 mg/day when used with indinavir, saquinavir, clarithromycin, ketoconazole 400 mg/day, atazanavir, or itraconazole 400 mg/day.
Cobicistat or ritonavir (600 mg every 12 hours): a dose of Vardenafil not to exceed 2.5 mg every 72 hours
500 mg of erythromycin every eight hours: 5 mg of Vardenafil daily.
Oral disintegrating tablet (ODT)
Strong or mild inhibitors of CYP3A4: Do not use (cannot adjust the dosage of Vardenafil).
Alpha blocker coadministration
Start Vardenafil only after stabilizing with an alpha-blocker.
Stabilized on alpha-blocker medication (such as alfuzosin, terazosin, or tamsulosin): 5 mg PO daily at first
stabilised on beta-blocker medicines and started on a moderate-to-strong CYP3A4 inhibitor (2.5 mg PO day).
When using Vardenafil concurrently with alpha-blocker medication, consider the interval between doses.
Limit grapefruit juice intake while using Vardenafil due to potential interactions. Avoid excessive alcohol consumption as it can worsen side effects. Exercise caution with nitrates, which may lead to possible hypotension—maintaining a healthy weight, balanced diet, and regular exercise support managing erectile dysfunction. Avoiding alcohol helps prevent exacerbating erectile difficulties while refraining from tobacco usage aids in mitigating its impact.
The dietary restriction should be individualized as per patient requirements.
Vardenafil may be contraindicated in the following conditions:-
- Anyone who has previously experienced hypersensitivity to any of the product's constituents.
- Soluble guanylate cyclase (sGC) stimulators (e.g., riociguat or vericiguat); concomitant use can cause hypotension.
- It enhances nitrate-induced hypotensive effects and is contraindicated when used alongside any form of organic nitrates.
- Use cautiously in patients with bleeding disorders, active peptic ulcer disease, liver disease, cardiovascular disease, left ventricular outflow obstruction, renal impairment, multidrug antihypertensive regimens, retinitis pigmentosa, concurrent use of CYP3A4 inhibitors, anatomical deformation of the penis (such as cavernosal fibrosis, angulation, or Peyronie's disease), patients with sickle cell anaemia, multiple myeloma, or leukaemia)
- Rare reports of painful erections lasting longer than six hours, or priapism, have been made for this class of drugs, which includes Vardenafil. Suppose an erection lasts longer than four hours. In that case, the patient should seek medical attention promptly because if priapism is not treated immediately, permanent loss of potency and penile tissue damage may occur.
- Physician needs to take their patients' cardiovascular health into account. Sexual activity carries a certain amount of danger for heart problems; thus, treating erectile dysfunction in men whose underlying cardiovascular condition prevents them from engaging in sexual activity is not advised.
- Drugs do not protect against sexually transmitted illnesses; instead, patients should be instructed on the precautions that need to be taken to prevent them, such as the Human Immunodeficiency Virus (HIV).
- When vision loss occurs suddenly in one or both eyes, it may indicate non-arteritic anterior ischemic optic neuropathy (NAION). Patients who have previously experienced NAION are more likely to experience recurrences. Use of this medication is not advised in patients with known degenerative retinal disorders.
- It may raise the chance of an uncommon, abrupt vision loss linked to nonarteritic ischemic optic neuropathy; if vision issues develop, stop using and speak with a physician.
- Individuals with congenital QT prolongation or those on Class 1A (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic drugs ought to abstain from using the drug.
- It is not advised to utilize medications that have not been thoroughly evaluated for their safety and effectiveness when combined with other treatments for erectile dysfunction.
- It is advised not to be taken with other phosphodiesterase (PDE)-5 inhibitors, such as tadalafil or sildenafil.
- Vasodilators, such as PDE5 inhibitors, can harm patients who have left ventricular outflow blockage, such as aortic stenosis and idiopathic hypertrophic subaortic stenosis.
- Use is not advised in cases of unstable angina, hypotension (resting systolic blood pressure of less than 90 mmHg), uncontrolled hypertension (less than 170/110 mmHg), recent history of stroke, life-threatening arrhythmia, or myocardial infarction (within the last six months), or severe cardiac failure until more information is available.
- The medication's systemic vasodilatory effects caused temporary drops in supine blood pressure in the healthy volunteers (mean maximum decreases of 7 mmHg systolic and eight mmHg diastolic). However, most patients would likely not be affected significantly by these vasodilatory effects, and doctors should carefully consider whether such effects may negatively impact their patients with underlying cardiovascular disease.
- PDE5 inhibitors, including Vardenafil, have been linked to sudden decreases in hearing and loss of consciousness. It is impossible to determine whether these events are caused by the use of PDE5 inhibitors or by other factors. Therefore, physicians should advise patients to stop taking all PDE5 inhibitors and to seek medical care immediately if they experience any of these symptoms.
Alcohol Warning
It is unsafe to consume Vardenafil with alcohol.
Breast Feeding Warning
It is not recommended for use during breastfeeding.
Pregnancy Warning
It is not recommended for use during pregnancy.
Food Warning
Limit grapefruit alcohol and take caution with nitrates.
The adverse reactions related to Vardenafil can be categorized as
Common Adverse Effects: Headache and flushing
Less Common Adverse Effects: Rhinitis, dyspepsia, flulike syndrome, sinusitis, back pain, dizziness, increased creatine phosphokinase, and nausea
Rare Adverse Effects: Anaphylaxis, angina, insomnia, myocardial infarction (MI), postural hypotension, priapism, pruritus, and rash.
The clinically relevant drug interactions of Vardenafil are briefly summarized here.
- Drug Interactions: When combined with anti-angina medications (nitroglycerin, amyl nitrite, butyl nitrate), a vasodilator (riociguat), an antiarrhythmic (quinidine, procainamide, amiodarone, sotalol), an alpha-blocker (tamsulosin, terazosin, alfuzosin), an anti-HIV medication (ritonavir, indinavir), and a calcium channel blocker (nifedipine), these medications may interact with denafil. If any herbal supplement called St. John's wort is utilized, notify the physician.
- Drug-Food Interactions: Grapefruit juice and Vardenafil may interact. As a result, avoid consuming grapefruit juice while taking Vardenafil, as this could raise Vardenafil concentrations and have higher adverse effects.
- Drug-Disease Interactions: Avoid taking Vardenafil in case of heart problems or liver problems, kidney dialysis, recently had a heart attack or stroke, low blood pressure, degenerative eye diseases, or non-arteritic ischemic optic neuropathy (loss of vision due to damage to optic nerve).
The common side effects of Vardenafil include:-
Flushing (sensation of warmth in the neck, trunk, ears, and face)
Headache
Blurred vision
Nausea
Indigestion
Dizziness
Muscle pain
Upset stomach
Rash
Stuffy nose caused by nasal congestion
Backaches
- Pregnancy
Pregnancy Category B (FDA): Could be acceptable. Either no danger has been shown by animal research, but human studies have not been conducted, or some risk has been shown by animal studies but not by human studies.
It is not indicated for women. The use of Vardenafil in pregnant women has not been studied.
Animal data
Rats and rabbits that were given Vardenafil at doses of up to 18 mg/kg/day throughout organogenesis showed no signs of particular risk for teratogenicity, embryotoxicity, or fetotoxicity. Based on the maximum recommended human dose (MRHD) of 20 mg, this dose is about 100 times (for rats) and 29 times (for rabbits) higher than the AUC values for unbound Vardenafil and its primary metabolite in humans.
- Nursing Mothers
The use of Vardenafil in females is not recommended. If Vardenafil is eliminated from human breast milk, this is unknown.
Animal data
Lactating rats released Vardenafil at amounts around ten times higher in their milk than in their plasma. Within 24 hours of a single oral dose of 3 mg/kg, 3.3% of the dose was eliminated into the milk.
- Pediatric Use
As per the FDA, safety and effectiveness in the pediatric population have not been established.
- Geriatric Use
Geriatric patients generally demonstrated safety and efficacy similar to younger adults with Vardenafil. However, caution is necessary due to potential age-related impacts on drug metabolism and cardiovascular health, requiring possible dose adjustments based on individual health status.
Data
Vardenafil plasma concentrations are more significant in elderly males 65 years of age and beyond than in younger guys (18 to 45); the mean Cmax and AUC were 34% and 52% higher, respectively. More than 834 older patients participated in phase 3 clinical studies; when Vardenafil HCl 5, 10, or 20 mg was given to these patients instead of younger ones, no differences in safety or efficacy were seen. However, individuals 65 or older should start with 5 mg of vardenafil hydrochloride due to increasing vardenafil concentrations in older people.
Dose Adjustment in Kidney Impairment Patients:
Mild-to-severe: No dosage adjustment is necessary.
Hemodialysis: Not recommended.
Dose Adjustment in Hepatic Impairment Patients:
Mild hepatic impairment: No dose adjustment is needed.
Moderate impairment: Start 5mg PO approximately 1 hr before sexual activity and not exceed 10 mg once daily.
Severe hepatic impairment: Not recommended.
Signs and Symptoms
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Vardenafil.
Overconsumption of Vardenafil could lead to prolonged erections, severe hypotension, dizziness, visual disturbances, and potential cardiac complications.
Management
There is no specific antidote or treatment for excessive Vardenafil intake, so treatment typically involves symptomatic and supportive measures. If ingestion is recent, promptly induce vomiting or perform gastric lavage. Manage symptoms such as hypotension or prolonged erections with appropriate interventions. Standard methods for treating prolonged erections include applying ice packs and relieving associated discomfort. Use intravenous fluids and vasopressors cautiously for severe hypotension. Continuous monitoring of cardiac function and vital signs is essential due to potential cardiovascular effects.
Consider activated charcoal to reduce further absorption within the appropriate timeframe. In severe cases, particularly with cardiovascular compromise, consider vasopressor support or specific antidotes if available and beneficial. Continuous observation and appropriate medical interventions are recommended to address particular symptoms or complications.
Pharmacodynamics:
Vardenafil is a potent and specific phosphodiesterase type 5 (PDE5) inhibitor, an enzyme that breaks down cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. Smooth muscle relaxation, an increase in blood flow, and an erection are caused by the presence of cGMP in the corpus cavernosum. Consequently, typical sexual excitement will raise cGMP levels in the corpus cavernosum of vardenafil-treated erectile dysfunction patients. Vardenafil shouldn't produce cGMP or generate an erection in the absence of sexual stimulation.
Men with underlying cardiovascular conditions for whom sexual activity is contraindicated shouldn't take Vardenafil. Additionally, priapism and persistent erections lasting longer than four hours are possible side effects. Patients are advised to stop using Vardenafil if they suddenly lose vision in one or both eyes—individuals using PDE5 inhibitors, including Vardenafil, risk experiencing a prolonged QT interval and unexpected hearing loss.
Pharmacokinetics:
Absorption
Vardenafil quickly absorbs from the gastrointestinal tract. The intake of food, especially high-fat meals, reduces absorption speed. Its bioavailability stands at around 15%. Peak plasma concentration occurs within 0.5-2 hours.
Distribution
Vardenafil extensively spreads across tissues, exhibiting a volume of distribution of 208 L. It appears in semen and binds to plasma proteins at around 95% for both the parent drug and metabolite.
Metabolism
The liver primarily metabolizes it through CYP3A4, CYP3A5, and CYP2C, transforming it via desethylation into an active metabolite.
Metabolites: M1 (active; plasma concentration 26% of the parent compound)
Elimination
It is eliminated primarily through faeces, accounting for around 91-95% as metabolites, and via urine, comprising approximately 2-6%. Its terminal half-life spans about 4-6 hours.
Total body clearance: 56 L/hr
Excretion: Feces (95%), urine (5%)
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Published on: 28 Nov 2023 5:14 AM GMT
