Vardenafil hydrochloride orally disintegrating tablets should be taken without liquid.DistributionThe mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution.
7.3 Effects of Vardenafil on Other Drugs
Vardenafil hydrochloride orally disintegrating tablets should be taken without liquid.DistributionThe mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution. Vardenafil and its major circulating metabolite, M1, are highly bound to plasma proteins (about 95% for parent drug and M1). This protein binding is reversible and independent of total drug concentrations.Following a single oral dose of 20 mg vardenafil film-coated tablet in healthy volunteers, a mean of 0.00018% of the administered dose was obtained in semen 1.5 hours after dosing.MetabolismVardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulating metabolite, M1, results from desethylation at the piperazine moiety of vardenafil. The plasma concentration of M1 is approximately 26% that of the parent compound.
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This metabolite shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil. Therefore, M1 accounts for approximately 7% of total pharmacologic activity.ExcretionThe mean terminal half-life of vardenafil in patients receiving vardenafil hydrochloride orally disintegrating tablets varied between about 4 to 6 hours. The elimination half-life of the metabolite M1 is between 3 to 5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91 to 95% of administered oral dose) and to a lesser extent in the urine (approximately 2 to 6% of administered oral dose). Vardenafil is a high clearance drug with a plasma clearance of 56.4 L/h following intravenous administration.Pharmacokinetics in Specific PopulationsPediatricsVardenafil hydrochloride orally disintegrating tablets are not indicated for use in pediatric patients.
Drug Interactions
Vardenafil trials were not conducted in the pediatric population.GeriatricsVardenafil AUC and Cmax in elderly patients (65 years or older) taking vardenafil hydrochloride orally disintegrating tablets were increased by 39% and 21%, respectively, in comparison to patients aged 45 years and below [see Use in Specific Populations (8.5)].Hepatic ImpairmentIn volunteers with mild hepatic impairment (Child-Pugh A), the Cmax and AUC following a 10 mg vardenafil (film-coated tablets) dose were increased by 22% and 17%, respectively, compared to healthy control subjects. Vardenafil has not been evaluated in patients with severe (Child-Pugh C) hepatic impairment [see Dosage and Administration (2.3), Warnings and Precautions (5.8), and Use in Specific Populations (8.6). ]Renal ImpairmentIn volunteers with mild renal impairment (CLcr = 50 to 80 mL/min), the pharmacokinetics of vardenafil were similar to those observed in a control group with normal renal function. Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis [see Dosage and Administration (2.3), Warnings and Precautions (5.9), and Use in Specific Populations (8.7)]. Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. Vardenafil and its major circulating metabolite, M1, are highly bound to plasma proteins (about 95% for parent drug and M1).
- Some users may experience mild flickering vision episodes.
- The efficacy of vardenafil varies between individuals.
- The medication is available in various dosage forms.
- Always follow the specific instructions provided.
- Avoid taking vardenafil with high-fat meals to speed absorption.
- Do not take vardenafil if allergic to its ingredients.
- The drug may cause a temporary burning sensation.
- Use caution in patients with a history of priapism.
- Avoid combining vardenafil with certain herbal supplements.
- Consult your doctor about any ongoing health treatments.
This protein binding is reversible and independent of total drug concentrations.Following a single oral dose of 20 mg vardenafil film-coated tablet in healthy volunteers, a mean of 0.00018% of the administered dose was obtained in semen 1.5 hours after dosing.MetabolismVardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulating metabolite, M1, results from desethylation at the piperazine moiety of vardenafil. The plasma concentration of M1 is approximately 26% that of the parent compound.
- Side effects can include headache, flushing, or stomach upset.
- Serious side effects are rare but require immediate medical attention.
- Vardenafil may cause changes in color vision.
- Use caution if using other medication for blood pressure.
- The medication helps improve erectile function temporarily.
- Do not share tablets with others.
- Follow storage instructions to maintain efficacy.
- Report any allergic reactions promptly.
- The drug should be used only under medical supervision.
- Used responsibly, vardenafil can improve quality of life.
This metabolite shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil. Therefore, M1 accounts for approximately 7% of total pharmacologic activity.ExcretionThe mean terminal half-life of vardenafil in patients receiving vardenafil hydrochloride orally disintegrating tablets varied between about 4 to 6 hours.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Levitra Generic | 20mg | 120 + 10 Pills | 224.15€ 213.48€ | |
| Kamagra Oral Jelly | 100 mg | 21 Sachets | 95.92€ 91.35€ | |
| Kamagra | 100mg | 60 + 4 Pills | 201.34€ 191.75€ | |
| Levitra Generic | 40mg | 360 + 10 Pills | 704.99€ 671.42€ | |
| Levitra Generic | 40mg | 60 + 4 Pills | 162.37€ 154.64€ | |
| Cialis Black | 80mg | 30 + 2 Pills | 89.11€ 84.87€ | |
| Kamagra Gold | 50 mg | 20 Pills | 73.17€ 69.69€ | |
| Tadalista Super Active | 20mg | 90 + 10 Pills | 314.14€ 299.18€ | |
| Viagra Super Active | 100mg | 10 Pills | 28.76€ 27.39€ | |
| Cialis Super Active | 20mg | 120 + 16 Pills | 382.15€ 363.95€ | |
| Cialis Generic | 2.5mg | 180 + 10 Pills | 154.86€ 147.49€ | |
| Kamagra Gold | 50 mg | 84 + 6 Pills | 224.77€ 214.07€ | |
| Viagra Oral Jelly | 100mg | 10 Sachets | 46.36€ 44.15€ | |
| Cialis Black | 80mg | 120 + 8 Pills | 264.77€ 252.16€ |
The elimination half-life of the metabolite M1 is between 3 to 5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91 to 95% of administered oral dose) and to a lesser extent in the urine (approximately 2 to 6% of administered oral dose). Vardenafil is a high clearance drug with a plasma clearance of 56.4 L/h following intravenous administration.Pharmacokinetics in Specific PopulationsPediatricsVardenafil hydrochloride orally disintegrating tablets are not indicated for use in pediatric patients. Vardenafil trials were not conducted in the pediatric population.GeriatricsVardenafil AUC and Cmax in elderly patients (65 years or older) taking vardenafil hydrochloride orally disintegrating tablets were increased by 39% and 21%, respectively, in comparison to patients aged 45 years and below [see Use in Specific Populations (8.5)].Hepatic ImpairmentIn volunteers with mild hepatic impairment (Child-Pugh A), the Cmax and AUC following a 10 mg vardenafil (film-coated tablets) dose were increased by 22% and 17%, respectively, compared to healthy control subjects. Vardenafil has not been evaluated in patients with severe (Child-Pugh C) hepatic impairment [see Dosage and Administration (2.3), Warnings and Precautions (5.8), and Use in Specific Populations (8.6). ]Renal ImpairmentIn volunteers with mild renal impairment (CLcr = 50 to 80 mL/min), the pharmacokinetics of vardenafil were similar to those observed in a control group with normal renal function.
| Region | Average Price (per tablet) | Availability | Notes |
|---|---|---|---|
| North America | $2 - $5 | Widely available | Prescription required |
| Europe | €2 - €4 | Available at pharmacies | Generic options common |
| Asia | $1 - $3 | Readily available | Often lower cost |
| Africa | $2 - $4 | Varies by country | May require import or special order |
Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis [see Dosage and Administration (2.3), Warnings and Precautions (5.9), and Use in Specific Populations (8.7)]. Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles.
What can cause erectile dysfunction?
Treatment & Diagnosis
Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has no effect in the absence of sexual stimulation. In vitro studies have shown that vardenafil is a selective inhibitor of PDE5.
14.1 Other Vardenafil Clinical Trials Using Film-Coated Tablets
The inhibitory effect of vardenafil is more selective on PDE5 men enhancement pills than for other known phosphodiesterases (>15-fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1,000-fold relative to PDE2, 3, 4, 7, 8, 9, and 10). The pharmacodynamic studies described below were conducted using vardenafil film-coated tablets.
| Storage Condition | Recommended Temperature | Humidity | Additional Notes |
|---|---|---|---|
| Standard Storage | 15-30°C (59-86°F) | < 70% | Keep away from light |
| Protect from moisture | - | Keep in a dry place | Keep in original container |
| Keep out of reach of children | - | - | Safety measure |
In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg film-coated tablets caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute. Vardenafil may add to the blood pressure lowering effects of antihypertensive agents [see Drug Interactions (7)]. Effects on Blood Pressure and Heart Rate when Vardenafil is Combined with Nitrates A study was conducted in which the blood pressure and heart rate response to 0.4 mg nitroglycerin (NTG) sublingually was evaluated in 18 healthy subjects following pretreatment with vardenafil 20 mg film-coated tablets at various times before NTG administration. Additional blood pressure and heart rate changes were not detected when vardenafil 20 mg film-coated tablet was dosed 24 hours before NTG (see Figure 1).
- Vardenafil 10 mg enhances natural erectile response.
- The medication is prescription-only in most countries.
- Common brand names include Levitra and Staxyn.
- Do not crush or split the tablet unless instructed.
- Using more than the prescribed dose can increase risk.
- Vardenafil is a phosphodiesterase inhibitor.
- It is not intended for use by women.
- Possible side effects include nasal congestion and dizziness.
- Seek medical advice if you experience priapism.
- Keep out of reach of children.
Figure 1: Placebo-subtracted point estimates (with 90% CI) of mean maximal blood pressure and heart rate effects of pre-dosing with vardenafil 20 mg at 24, 8, 4, and 1 hour before 0.4 mg NTG sublingually Because the disease state of patients requiring nitrate therapy is anticipated to increase the likelihood of hypotension, the use of vardenafil by patients on nitrate therapy or on nitric oxide donors is contraindicated [see Contraindications (4.1)]. Blood Pressure Effects in Patients on Stable Alpha-Blocker Treatment Three clinical pharmacology studies were conducted in patients with benign prostatic hyperplasia (BPH) on stable-dose alpha-blocker treatment , consisting of alfuzosin, tamsulosin or terazosin. Study 1: This study was designed to evaluate the effect of 5 mg vardenafil film-coated tablets compared to placebo when administered to BPH patients on chronic alpha-blocker therapy in two separate cohorts: tamsulosin 0.4 mg daily (cohort 1, n=21) and terazosin 5 or 10 mg daily (cohort 2, n=21). Table 2: Mean (95% CI) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 5 mg in BPH patients on stable alpha-blocker therapy (study 1) Blood pressure effects (standing SBP) in normotensive men on stable dose tamsulosin 0.4 mg following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours are shown in Figure 2.
Key Takeaways
Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has no effect in the absence of sexual stimulation. In vitro studies have shown that vardenafil is a selective inhibitor of PDE5. The inhibitory effect of vardenafil is more selective on PDE5 men enhancement pills than for other known phosphodiesterases (>15-fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1,000-fold relative to PDE2, 3, 4, 7, 8, 9, and 10). The pharmacodynamic studies described below were conducted using vardenafil film-coated tablets. In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg film-coated tablets caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute.
What should I know about vardenafil before taking it?
Vardenafil may add to the blood pressure lowering effects of antihypertensive agents [see Drug Interactions (7)]. Effects on Blood Pressure and Heart Rate when Vardenafil is Combined with Nitrates A study was conducted in which the blood pressure and heart rate response to 0.4 mg nitroglycerin (NTG) sublingually was evaluated in 18 healthy subjects following pretreatment with vardenafil 20 mg film-coated tablets at various times before NTG administration. Additional blood pressure and heart rate changes were not detected when vardenafil 20 mg film-coated tablet was dosed 24 hours before NTG (see Figure 1). Figure 1: Placebo-subtracted point estimates (with 90% CI) of mean maximal blood pressure and heart rate effects of pre-dosing with vardenafil 20 mg at 24, 8, 4, and 1 hour before 0.4 mg NTG sublingually Because the disease state of patients requiring nitrate therapy is anticipated to increase the likelihood of hypotension, the use of vardenafil by patients on nitrate therapy or on nitric oxide donors is contraindicated [see Contraindications (4.1)]. Blood Pressure Effects in Patients on Stable Alpha-Blocker Treatment Three clinical pharmacology studies were conducted in patients with benign prostatic hyperplasia (BPH) on stable-dose alpha-blocker treatment , consisting of alfuzosin, tamsulosin or terazosin.
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Study 1: This study was designed to evaluate the effect of 5 mg vardenafil film-coated tablets compared to placebo when administered to BPH patients on chronic alpha-blocker therapy in two separate cohorts: tamsulosin 0.4 mg daily (cohort 1, n=21) and terazosin 5 or 10 mg daily (cohort 2, n=21). Table 2: Mean (95% CI) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 5 mg in BPH patients on stable alpha-blocker therapy (study 1) Blood pressure effects (standing SBP) in normotensive men on stable dose tamsulosin 0.4 mg following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours are shown in Figure 2. Blood pressure effects (standing SBP) in normotensive men on stable dose terazosin (5 or 10 mg) following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours, are shown in Figure 3. Figure 2: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (study 1) Figure 3: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose terazosin (5 or 10 mg) in normotensive BPH patients (study 1) Study 2: This study was designed to evaluate the effect of 10 mg vardenafil (film-coated tablets) (stage 1) and 20 mg vardenafil (film-coated tablets) (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=23) on stable therapy with tamsulosin 0.4 mg or 0.8 mg daily for at least four weeks. Table 3: Mean (95% CI) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 10 and 20 mg (film-coated tablets) in BPH patients on stable alpha-blocker therapy with tamsulosin 0.4 or 0.8 mg daily (study 2) Blood pressure effects (standing SBP) in normotensive men on stable dose of tamsulosin 0.4 mg following simultaneous administration of vardenafil 10 mg, vardenafil 20 mg or placebo are shown in Figure 4. Blood pressure effects (standing SBP) in normotensive men on stable dose terazosin (5 or 10 mg) following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours, are shown in Figure 3. Figure 2: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (study 1) Figure 3: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose terazosin (5 or 10 mg) in normotensive BPH patients (study 1) Study 2: This study was designed to evaluate the effect of 10 mg vardenafil (film-coated tablets) (stage 1) and 20 mg vardenafil (film-coated tablets) (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=23) on stable therapy with tamsulosin 0.4 mg or 0.8 mg daily for at least four weeks.
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Table 3: Mean (95% CI) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 10 and 20 mg (film-coated tablets) in BPH patients on stable alpha-blocker therapy with tamsulosin 0.4 or 0.8 mg daily (study 2) Blood pressure effects (standing SBP) in normotensive men on stable dose of tamsulosin 0.4 mg following simultaneous administration of vardenafil 10 mg, vardenafil 20 mg or placebo are shown in Figure 4. Figure 4: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous administration of vardenafil 10 mg film-coated tablet (stage 1), vardenafil 20 mg film-coated tablet (Stage 2), or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (study 2) Study 3: This study was designed to evaluate the effect of single doses of 5 mg vardenafil (stage 1) and 10 mg vardenafil (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=24) on stable therapy with alfuzosin 10 mg daily for at least four weeks.
What is the competitive landscape?
Figure 4: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous administration of vardenafil 10 mg film-coated tablet (stage 1), vardenafil 20 mg film-coated tablet (Stage 2), or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (study 2) Study 3: This study was designed to evaluate the effect of single doses of 5 mg vardenafil (stage 1) and 10 mg vardenafil (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=24) on stable therapy with alfuzosin 10 mg daily for at least four weeks. Table 4: Mean (95% C.I.) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 5 and 10 mg in BPH patients on stable alpha-blocker therapy with alfuzosin 10 mg daily (Study 3) One patient experienced decreases from baseline in standing systolic blood pressure >30 mm Hg after administration of vardenafil 5 mg film-coated tablets and vardenafil 10 mg film-coated tablets. Blood pressure effects (standing SBP) in normotensive men on a stable dose of alfuzosin 10 mg following administration of vardenafil 5 mg, vardenafil 10 mg, or placebo separated by 4 hours, are shown in Figure 5. Figure 5: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following 4 hr separation administration of vardenafil 5 mg (stage 1), vardenafil 10 mg (stage 2) or placebo with stable dose alfuzosin 10 mg in BPH patients (Study 3) Blood Pressure Effects in Normotensive Men After Forced Titration with Alpha-Blockers Two randomized, double blind, placebo-controlled clinical pharmacology studies with healthy normotensive volunteers (age range, 45 to 74 years) were performed after forced titration of the alpha-blocker terazosin to 10 mg daily over 14 days (n=29), and after initiation of tamsulosin 0.4 mg daily for five days (n=24). Instances of outlier blood pressure values (defined as standing SBP <85 mmHg and/or a decrease from baseline of standing SBP >30 mmHg) were observed in 9/24 subjects receiving tamsulosin and 19/29 receiving terazosin.
Less common
The incidence of subjects with standing SBP <85 mmHg given vardenafil and terazosin to achieve simultaneously the amount of time at the maximum concentration in serum (Tmax) led to early termination of that arm of the study.
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Table 4: Mean (95% C.I.) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 5 and 10 mg in BPH patients on stable alpha-blocker therapy with alfuzosin 10 mg daily (Study 3) One patient experienced decreases from baseline in standing systolic blood pressure >30 mm Hg after administration of vardenafil 5 mg film-coated tablets and vardenafil 10 mg film-coated tablets.
| Parameter | Result | Notes |
|---|---|---|
| Absorption Time | 30-60 minutes | Time to peak plasma concentration (Tmax) |
| Bioavailability | ~15% | Percentage of dose reaching systemic circulation |
| Half-life | 4-5 hours | Duration of effect |
| Metabolism | Liver (CYP3A4 enzyme) | Mainly via hepatic pathways |
| Excretion | Feces (~60%), Urine (~20%) | Primary routes |
Blood pressure effects (standing SBP) in normotensive men on a stable dose of alfuzosin 10 mg following administration of vardenafil 5 mg, vardenafil 10 mg, or placebo separated by 4 hours, are shown in Figure 5. Figure 5: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following 4 hr separation administration of vardenafil 5 mg (stage 1), vardenafil 10 mg (stage 2) or placebo with stable dose alfuzosin 10 mg in BPH patients (Study 3) Blood Pressure Effects in Normotensive Men After Forced Titration with Alpha-Blockers Two randomized, double blind, placebo-controlled clinical pharmacology studies with healthy normotensive volunteers (age range, 45 to 74 years) were performed after forced titration of the alpha-blocker terazosin to 10 mg daily over 14 days (n=29), and after initiation of tamsulosin 0.4 mg daily for five days (n=24). Instances of outlier blood pressure values (defined as standing SBP <85 mmHg and/or a decrease from baseline of standing SBP >30 mmHg) were observed in 9/24 subjects receiving tamsulosin and 19/29 receiving terazosin. The incidence of subjects with standing SBP <85 mmHg given vardenafil and terazosin to achieve simultaneously the amount of time at the maximum concentration in serum (Tmax) led to early termination of that arm of the study.