Clinical Benefits of Low-Dose Vardenafil Treatment

LEVITRA is formulated as orange, round, film-coated tablets with “BAYER” cross debossed on one side and “2.5”, “5”, “10”, and “20” on the other side corresponding to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively. Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMP-specific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP. 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 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 pharmacokinetics of vardenafil are approximately dose proportional over the recommended dose range. Vardenafil is eliminated predominantly by hepatic metabolism, mainly by CYP3A4 and to a minor extent, CYP2C isoforms. Concomitant use with potent CYP3A4 inhibitors such as ritonavir, indinavir, ketoconazole, as well as moderate CYP3A inhibitors such as erythromycin results in significant increases of plasma levels of vardenafil (see PRECAUTIONS, WARNINGS and DOSAGE AND ADMINISTRATION).

• Vardenafil 5 mg may be less effective if taken with high-fat meals.
• Side effects like indigestion or muscle aches are possible.
• Inform your doctor about any allergic reactions experienced.
• Be cautious if you have low blood pressure or heart disease.
• It is recommended to avoid taking other ED medications concurrently.
• Regular check-ups help assess medication effectiveness.
• Discontinue use and seek help if adverse reactions occur.
• The medication can improve intimacy confidence and quality.
• Use the lowest effective dose to minimize side effects.
• Vardenafil 5 mg is generally safe when used responsibly.
• Keep out of reach of children and pets.
• Consult your healthcare provider for personalized advice.

Mean vardenafil plasma concentrations measured after the administration of a single oral dose of 20 mg to healthy male volunteers are depicted in Figure 1. Figure 1: Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg LEVITRA Dose Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. Maximum observed plasma concentrations after a single 20 mg dose in healthy volunteers are usually reached between 30 minutes and 2 hours (median 60 minutes) after oral dosing in the fasted state. Two food-effect studies were conducted which showed that high-fat meals caused a reduction in Cmax by 18%-50%. The mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution.

Shipping & Delivery

Following a single oral dose of 20 mg vardenafil in healthy volunteers, a mean of 0.00018% of the administered dose was obtained in semen 1.5 hours after dosing. Vardenafil 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. This metabolite shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for super p force uk PDE5 28% of that of vardenafil.

Can vardenafil and tadalafil be taken together?

Therefore, M1 accounts for approximately 7% of total pharmacologic activity. The total body clearance of vardenafil is 56 L/h, and the terminal half-life of vardenafil and its primary metabolite (M1) is approximately 4-5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose). Pediatrics: Vardenafil trials were not conducted in the pediatric population. Geriatrics: In a healthy volunteer study of elderly males (≥65 years) and younger males (18–45 years), mean Cmax and AUC were 34% and 52% higher, respectively, in the elderly males (see PRECAUTIONS, Geriatric Use and DOSAGE AND ADMINISTRATION). 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.

• Vardenafil 5 mg is not suitable for individuals taking certain heart medications.
• The medication may cause dizziness or lightheadedness in some users.
• Proper storage extends shelf life and maintains potency.
• Lifestyle factors like stress can impact treatment success.
• Avoid heavy meals before taking Vardenafil 5 mg to speed absorption.
• The medication does not work without sexual stimulation.
• Be aware of potential interactions with other prescribed drugs.
• Patients should avoid driving if feeling dizzy after taking it.
• Consult your doctor if you experience prolonged or painful erections.
• Vardenafil 5 mg has a rapid onset but variable duration.
• It is important to review medical history before starting therapy.
• Combination therapy with other ED treatments should only be under medical supervision.

Following a single oral dose of 20 mg vardenafil in healthy volunteers, a mean of 0.00018% of the administered dose was obtained in semen 1.5 hours after dosing. Vardenafil 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. This metabolite shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for super p force uk PDE5 28% of that of vardenafil. Therefore, M1 accounts for approximately 7% of total pharmacologic activity. The total body clearance of vardenafil is 56 L/h, and the terminal half-life of vardenafil and its primary metabolite (M1) is approximately 4-5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose).

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Pediatrics: Vardenafil trials were not conducted in the pediatric population.

More about vardenafil

The pharmacokinetics of vardenafil are approximately dose proportional over the recommended dose range. Vardenafil is eliminated predominantly by hepatic metabolism, mainly by CYP3A4 and to a minor extent, CYP2C isoforms. Concomitant use with potent CYP3A4 inhibitors such as ritonavir, indinavir, ketoconazole, as well as moderate CYP3A inhibitors such as erythromycin results in significant increases of plasma levels of vardenafil (see PRECAUTIONS, WARNINGS and DOSAGE AND ADMINISTRATION). Mean vardenafil plasma concentrations measured after the administration of a single oral dose of 20 mg to healthy male volunteers are depicted in Figure 1. Figure 1: Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg LEVITRA Dose Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%.

Other Interactions

Maximum observed plasma concentrations after a single 20 mg dose in healthy volunteers are usually reached between 30 minutes and 2 hours (median 60 minutes) after oral dosing in the fasted state. Two food-effect studies were conducted which showed that high-fat meals caused a reduction in Cmax by 18%-50%. The 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. Geriatrics: In a healthy volunteer study of elderly males (≥65 years) and younger males (18–45 years), mean Cmax and AUC were 34% and 52% higher, respectively, in the elderly males (see PRECAUTIONS, Geriatric Use and DOSAGE AND ADMINISTRATION). Consequently, a lower starting dose of LEVITRA (5 mg) in patients ≥65 years of age should be considered.

Patients & methods

The 80 mg dose of LEVITRA (four times the highest recommended dose) was chosen because this dose yields plasma concentrations covering those observed upon co-administration of a low-dose of LEVITRA (5 mg) and 600 mg BID of ritonavir. Of the CYP3A4 inhibitors that have been studied, ritonavir causes the most significant drug-drug interaction with vardenafil. Table 1 summarizes the effect on mean uncorrected QT and mean corrected QT interval (QTc) with different methods of correction (Fridericia and a linear individual correction method) at one hour post-dose. No single correction method is known to be more valid than the other. In this study, the mean increase in heart rate associated with a 10 mg dose of LEVITRA compared to placebo was 5 beats/minute and with an 80 mg dose of LEVITRA the mean increase was 6 beats/minute.

Synonym (SY): Vardenafil 5 mg (vardenafil hydrochloride 5.926 mg) Oral Tablet (Atom ID: 3274158)

Therapeutic and supratherapeutic doses of vardenafil and the active control moxifloxacin produced similar increases in QTc interval. This study, however, was not designed to make direct statistical comparisons between the drug or the dose levels. The clinical impact of these QTc changes is unknown (see PRECAUTIONS). In a separate postmarketing study of 44 healthy volunteers, single doses of 10 mg LEVITRA resulted in a placebo-subtracted mean change from baseline of QTcF (Fridericia correction) of 5 msec (90% CI: 2,8). Single doses of gatifloxacin 400mg resulted in a placebo-subtracted mean change from baseline QTcF of 4 msec (90% CI: 1,7). Renal Insufficiency: In volunteers with mild renal impairment (CLcr = 50-80 ml/min), the pharmacokinetics of vardenafil were similar to those observed in a control group with normal renal function.

Advancing Effective Research Policy

Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1. Vardenafil may add to the blood pressure lowering effects of antihypertensive agents (see PRECAUTIONS, Drug Interactions). 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 LEVITRA 20 mg at various times before NTG administration. LEVITRA 20 mg caused an additional time-related reduction in blood pressure and increase in heart rate in association with NTG administration. The blood pressure effects were observed when LEVITRA 20 mg was dosed 1 or 4 hours before NTG and the heart rate effects were observed when 20 mg was dosed 1, 4, or 8 hours before NTG.

Are vardenafil and tadalafil available over the counter?

Additional blood pressure and heart rate changes were not detected when LEVITRA 20 mg was dosed 24 hours before NTG. Figure 2: Placebo-subtracted point estimates (with 90% CI) of mean maximal blood pressure and heart rate effects of pre-dosing with LEVITRA 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 cenforce 100mg tablet is contraindicated (see CONTRAINDICATIONS). The effect of 10 mg and 80 mg vardenafil on QT interval was evaluated in a single-dose, double-blind, randomized, placebo- and active-controlled (moxifloxacin 400 mg) crossover study in 59 healthy males (81% White, 12% Black, 7% Hispanic) aged 45-60 years. The QT interval was measured at one hour post dose because this time point approximates the average time of peak vardenafil concentration. In the moderate (CLcr = 30-50 ml/min) or severe (CLcr<30 ml/min) renal impairment groups, the AUC of vardenafil was 20–30% higher compared to that observed in a control group with normal renal function (CLcr>80 ml/min). Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis (see PRECAUTIONS, Renal Insufficiency, and DOSAGE AND ADMINISTRATION). Hepatic Insufficiency: In volunteers with mild hepatic impairment (Child-Pugh A), the Cmax and AUC following a 10 mg vardenafil dose were increased by 22% and 17%, respectively, compared to healthy control subjects.

• Vardenafil 5 mg is used to treat erectile dysfunction in men.
• It works by increasing blood flow to the penis.
• Vardenafil 5 mg usually starts working within 30-60 minutes.
• The typical dosage for Vardenafil 5 mg is once daily.
• It is available by prescription only.
• Vardenafil 5 mg may cause side effects like headache or flushing.
• It is more effective when taken on an empty stomach.
• Alcohol can increase the risk of side effects with Vardenafil.
• Do not take Vardenafil 5 mg with nitrates or certain medications.
• Store Vardenafil 5 mg in a cool, dry place away from children.
• Consult your doctor before starting Vardenafil 5 mg.
• Report any persistent or severe side effects to your doctor.

In volunteers with moderate hepatic impairment (Child-Pugh B), the Cmax and AUC following a 10 mg vardenafil dose were increased by 130% and 160%, respectively, compared to healthy control subjects. Consequently, a starting dose of 5 mg is recommended for patients with moderate hepatic impairment, and the maximum dose should not exceed 10 mg (see PRECAUTIONS and DOSAGE AND ADMINISTRATION). Vardenafil has not been evaluated in patients with severe (Child-Pugh C) hepatic impairment. In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg 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. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1. Vardenafil may add to the blood pressure lowering effects of antihypertensive agents (see PRECAUTIONS, Drug Interactions). 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 LEVITRA 20 mg at various times before NTG administration. LEVITRA 20 mg caused an additional time-related reduction in blood pressure and increase in heart rate in association with NTG administration.

Related/similar drugs

When LEVITRA 10mg and gatifloxacin 400 mg were co-administered, the mean QTcF change from baseline was additive when compared to either drug alone and produced a mean QTcF change of 9 msec from baseline (90% CI: 6,11). The clinical impact of these QT changes is unknown (see PRECAUTIONS, Congenital or Acquired QT Prolongation). In two independent trials that assessed 10 mg (n=41) and 20 mg (n=39) vardenafil, respectively, vardenafil did not alter the total treadmill exercise time compared to placebo. The patient population included men aged 40-80 years with stable exercise-induced angina documented by at least one of the following: 1) prior history of MI, CABG, PTCA, or stenting (not within 6 months); 2) positive coronary angiogram showing at least 60% narrowing of the diameter of at least one major coronary artery; or 3) a positive stress echocardiogram or stress nuclear perfusion study. The blood pressure effects were observed when LEVITRA 20 mg was dosed 1 or 4 hours before NTG and the heart rate effects were observed when 20 mg was dosed 1, 4, or 8 hours before NTG.

Step	Description	Tips
Taking the medication	Take orally with a glass of water	Can be taken with or without food
Timing before sexual activity	30-60 minutes prior	Avoid heavy fatty meal initially
Duration of effect	Up to 4-5 hours, depending on individual	Be aware of your response
Do not exceed prescribed dose	Usually 5 mg per dose, once per day	Overdose risks and side effects

Additional blood pressure and heart rate changes were not detected when LEVITRA 20 mg was dosed 24 hours before NTG.

• Vardenafil 5 mg may require dose adjustment based on response.
• The medication can be combined with lifestyle changes for better results.
• Commonly prescribed for men aged 40-70 years.
• It is safe when used as directed under medical supervision.
• Avoid grapefruit juice while taking Vardenafil 5 mg.
• It can interact with certain antibiotics and antifungals.
• Female partners should also be aware of medication effects.
• The medication’s effectiveness depends on sexual stimulation.
• Do not use Vardenafil 5 mg if you have a recent heart attack.
• Be aware of possible visual disturbances as a side effect.
• Emergency medical attention is needed if an erection lasts over 4 hours.
• Proper hydration can help minimize side effects.

Figure 2: Placebo-subtracted point estimates (with 90% CI) of mean maximal blood pressure and heart rate effects of pre-dosing with LEVITRA 20 mg at 24, 8, 4, and 1 hour before 0.4 mg NTG sublingually.

Dosing & Uses

LEVITRA is formulated as orange, round, film-coated tablets with “BAYER” cross debossed on one side and “2.5”, “5”, “10”, and “20” on the other side corresponding to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively. Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection.

Does vardenafil interact with other medicines (drug interactions)?

The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMP-specific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP. 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 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). 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 cenforce 100mg tablet is contraindicated (see CONTRAINDICATIONS). The effect of 10 mg and 80 mg vardenafil on QT interval was evaluated in a single-dose, double-blind, randomized, placebo- and active-controlled (moxifloxacin 400 mg) crossover study in 59 healthy males (81% White, 12% Black, 7% Hispanic) aged 45-60 years. The QT interval was measured at one hour post dose because this time point approximates the average time of peak vardenafil concentration. The 80 mg dose of LEVITRA (four times the highest recommended dose) was chosen because this dose yields plasma concentrations covering those observed upon co-administration of a low-dose of LEVITRA (5 mg) and 600 mg BID of ritonavir. Of the CYP3A4 inhibitors that have been studied, ritonavir causes the most significant drug-drug interaction with vardenafil. Table 1 summarizes the effect on mean uncorrected QT and mean corrected QT interval (QTc) with different methods of correction (Fridericia and a linear individual correction method) at one hour post-dose. No single correction method is known to be more valid than the other. In this study, the mean increase in heart rate associated with a 10 mg dose of LEVITRA compared to placebo was 5 beats/minute and with an 80 mg dose of LEVITRA the mean increase was 6 beats/minute. Therapeutic and supratherapeutic doses of vardenafil and the active control moxifloxacin produced similar increases in QTc interval. This study, however, was not designed to make direct statistical comparisons between the drug or the dose levels. The clinical impact of these QTc changes is unknown (see PRECAUTIONS). In a separate postmarketing study of 44 healthy volunteers, single doses of 10 mg LEVITRA resulted in a placebo-subtracted mean change from baseline of QTcF (Fridericia correction) of 5 msec (90% CI: 2,8).

Aspect	Description	Typical Dosage	Onset Time	Duration of Action
Vardenafil 5 mg	A medication used to treat erectile dysfunction	5 mg	30-60 min	Up to 4-5 hours
Pharmacological Class	Phosphodiesterase type 5 inhibitor	N/A	N/A	N/A
Brand Names	Levitra, Staxyn (dissolvable film)	N/A	N/A	N/A

Single doses of gatifloxacin 400mg resulted in a placebo-subtracted mean change from baseline QTcF of 4 msec (90% CI: 1,7). When LEVITRA 10mg and gatifloxacin 400 mg were co-administered, the mean QTcF change from baseline was additive when compared to either drug alone and produced a mean QTcF change of 9 msec from baseline (90% CI: 6,11). The clinical impact of these QT changes is unknown (see PRECAUTIONS, Congenital or Acquired QT Prolongation). In two independent trials that assessed 10 mg (n=41) and 20 mg (n=39) vardenafil, respectively, vardenafil did not alter the total treadmill exercise time compared to placebo.

What is vardenafil?

Consequently, a lower starting dose of LEVITRA (5 mg) in patients ≥65 years of age should be considered. Renal Insufficiency: In volunteers with mild renal impairment (CLcr = 50-80 ml/min), the pharmacokinetics of vardenafil were similar to those observed in a control group with normal renal function. In the moderate (CLcr = 30-50 ml/min) or severe (CLcr<30 ml/min) renal impairment groups, the AUC of vardenafil was 20–30% higher compared to that observed in a control group with normal renal function (CLcr>80 ml/min). Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis (see PRECAUTIONS, Renal Insufficiency, and DOSAGE AND ADMINISTRATION). Hepatic Insufficiency: In volunteers with mild hepatic impairment (Child-Pugh A), the Cmax and AUC following a 10 mg vardenafil dose were increased by 22% and 17%, respectively, compared to healthy control subjects.

Medications & Supplements

In volunteers with moderate hepatic impairment (Child-Pugh B), the Cmax and AUC following a 10 mg vardenafil dose were increased by 130% and 160%, respectively, compared to healthy control subjects. Consequently, a starting dose of 5 mg is recommended for patients with moderate hepatic impairment, and the maximum dose should not exceed 10 mg (see PRECAUTIONS and DOSAGE AND ADMINISTRATION). Vardenafil has not been evaluated in patients with severe (Child-Pugh C) hepatic impairment. In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg 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. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. The patient population included men aged 40-80 years with stable exercise-induced angina documented by at least one of the following: 1) prior history of MI, CABG, PTCA, or stenting (not within 6 months); 2) positive coronary angiogram showing at least 60% narrowing of the diameter of at least one major coronary artery; or 3) a positive stress echocardiogram or stress nuclear perfusion study.