Label: VARDENAFIL tablet, orally disintegrating

placebo: 433±109 and 426±105 seconds, respectively; 20 mg vardenafil vs. placebo: 414±114 and 411±124 seconds, respectively). The total time to angina was not altered by vardenafil when compared to placebo (10 mg vardenafil vs. placebo: 291±123 and 292±110 seconds; 20 mg vardenafil vs. placebo: 354±137 and 347±143 seconds, respectively).

Side Effects

The total time to 1 mm or greater ST-segment depression was similar to placebo in both the 10 mg and the 20 mg vardenafil groups (10 mg vardenafil vs. placebo: 380±108 and 334±108 seconds; 20 mg vardenafil vs. placebo: 364±101 and 366±105 seconds, respectively).Effects on EyeSingle oral doses of phosphodiesterase inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green) using the Farnsworth-Munsell 100-hue (FM-100) test and reductions in electroretinogram (ERG) b-wave amplitudes, with peak effects near the time of peak plasma levels. These findings are consistent with the inhibition of PDE6 in rods and cones, which is involved in phototransduction in the retina. The findings were most evident one hour after administration, diminishing but still present 6 hours after administration. In a single dose study in 25 normal males, vardenafil (film-coated tablets) 40 mg, twice the maximum daily recommended dose, did not alter visual acuity, intraocular pressure, fundoscopic and slit lamp findings.In another double-blind, placebo-controlled clinical trial, at least 15 doses of 20 mg vardenafil were administered over 8 weeks versus placebo to 52 males.

Thirty-two (32) males (62% of the patients) completed the trial. Retinal function was measured by ERG and FM-100 test 2, 6 and 24 hours after dosing. The trial was designed to detect changes in retinal function that might occur in more than 10% of patients.

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Vardenafil hydrochloride orally disintegrating tablets can be taken with or without food.Effect of water: When vardenafil hydrochloride orally disintegrating tablets were swallowed with water, the AUC of vardenafil was reduced by 29% and median Tmax was shortened by 60 minutes while Cmax was not affected. In clinical trials, dosing was done without water. 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.

Vardenafil Side Effects

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 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 erectile dysfunction tablets uk 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. Vardenafil did not produce clinically significant ERG or FM-100 effects in healthy men compared to placebo. Two patients on vardenafil in the trial reported episodes of transient cyanopsia (objects appear blue).Effects on Sperm Motility MorphologyThere was no effect on sperm motility or morphology after single 20 mg oral doses of vardenafil film-coated tablets in healthy volunteers.12.3 PharmacokineticsThe pharmacokinetics of vardenafil and its M1 metabolite from vardenafil hydrochloride orally disintegrating tablets have been evaluated in healthy male volunteers (18 to 50 years) and in young (18 to 45 years) and elderly (≥ 65 years) erectile dysfunction patients. Studies have shown that vardenafil hydrochloride orally disintegrating tablets provides higher systemic exposure of vardenafil compared to vardenafil 10 mg film-coated tablets.AbsorptionMean vardenafil plasma concentrations measured after the administration of a single oral dose vardenafil hydrochloride orally disintegrating tablets to patients with erectile dysfunction (18 to 45 years) are depicted in Figure 8.Figure 8: Vardenafil Plasma Concentration (Mean ± SD) Profile for Vardenafil Hydrochloride Orally Disintegrating Tablets in men age 18to 45 years with erectile dysfunctionThe median time to reach Cmax (Tmax) in patients receiving vardenafil hydrochloride orally disintegrating tablets in the fasted state was 1.5 h [range: 0.75 to 2.5 h].

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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. 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).

Drug Interactions

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. After administration of vardenafil hydrochloride orally disintegrating tablets to elderly (≥ 65 years) and young (18 to 45 years) patients with erectile dysfunction, mean vardenafil AUC was increased by 21 to 29%, respectively while mean Cmax was lower by 19% and 8%, respectively, in comparison to 10 mg vardenafil (film-coated tablets).

In a study of healthy male volunteers (18 to 50 years), the mean Cmax and AUC of vardenafil from vardenafil hydrochloride orally disintegrating tablets were higher by 15% and 44%, respectively compared to 10 mg vardenafil film-coated tablets.Vardenafil was not found to accumulate in plasma when vardenafil hydrochloride orally disintegrating tablets was dosed daily over ten days.Effect of food: A high fat meal had no effect on vardenafil AUC and Tmax from vardenafil hydrochloride orally disintegrating tablets in healthy volunteers and reduced Cmax by 35%. Clinical trials for vardenafil hydrochloride orally disintegrating tablets were conducted without regard to meals. Vardenafil hydrochloride orally disintegrating tablets can be taken with or without food.Effect of water: When vardenafil hydrochloride orally disintegrating tablets were swallowed with water, the AUC of vardenafil was reduced by 29% and median Tmax was shortened by 60 minutes while Cmax was not affected. In clinical trials, dosing was done without water. 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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In a single dose study in 25 normal males, vardenafil (film-coated tablets) 40 mg, twice the maximum daily recommended dose, did not alter visual acuity, intraocular pressure, fundoscopic and slit lamp findings.In another double-blind, placebo-controlled clinical trial, at least 15 doses of 20 mg vardenafil were administered over 8 weeks versus placebo to 52 males. Thirty-two (32) males (62% of the patients) completed the trial. Retinal function was measured by ERG and FM-100 test 2, 6 and 24 hours after dosing. The trial was designed to detect changes in retinal function that might occur in more than 10% of patients. Vardenafil did not produce clinically significant ERG or FM-100 effects in healthy men compared to placebo.

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Two patients on vardenafil in the trial reported episodes of transient cyanopsia (objects appear blue).Effects on Sperm Motility MorphologyThere was no effect on sperm motility or morphology after single 20 mg oral doses of vardenafil film-coated tablets in healthy volunteers.12.3 PharmacokineticsThe pharmacokinetics of vardenafil and its M1 metabolite from vardenafil hydrochloride orally disintegrating tablets have been evaluated in healthy male volunteers (18 to 50 years) and in young (18 to 45 years) and elderly (≥ 65 years) erectile dysfunction patients. Studies have shown that vardenafil hydrochloride orally disintegrating tablets provides higher systemic exposure of vardenafil compared to vardenafil 10 mg film-coated tablets.AbsorptionMean vardenafil plasma concentrations measured after the administration of a single oral dose vardenafil hydrochloride orally disintegrating tablets to patients with erectile dysfunction (18 to 45 years) are depicted in Figure 8.Figure 8: Vardenafil Plasma Concentration (Mean ± SD) Profile for Vardenafil Hydrochloride Orally Disintegrating Tablets in men age 18to 45 years with erectile dysfunctionThe median time to reach Cmax (Tmax) in patients receiving vardenafil hydrochloride orally disintegrating tablets in the fasted state was 1.5 h [range: 0.75 to 2.5 h]. After administration of vardenafil hydrochloride orally disintegrating tablets to elderly (≥ 65 years) and young (18 to 45 years) patients with erectile dysfunction, mean vardenafil AUC was increased by 21 to 29%, respectively while mean Cmax was lower by 19% and 8%, respectively, in comparison to 10 mg vardenafil (film-coated tablets). In a study of healthy male volunteers (18 to 50 years), the mean Cmax and AUC of vardenafil from vardenafil hydrochloride orally disintegrating tablets were higher by 15% and 44%, respectively compared to 10 mg vardenafil film-coated tablets.Vardenafil was not found to accumulate in plasma when vardenafil hydrochloride orally disintegrating tablets was dosed daily over ten days.Effect of food: A high fat meal had no effect on vardenafil AUC and Tmax from vardenafil hydrochloride orally disintegrating tablets in healthy volunteers and reduced Cmax by 35%. Clinical trials for vardenafil hydrochloride orally disintegrating tablets were conducted without regard to meals. 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.

• Vardenafil 10 mg should not be used with certain medications.
• Grapefruit or grapefruit juice may have interactions.
• Inform your doctor about all health conditions before use.
• The medication may cause vision changes or sensitivity.
• Do not use vardenafil if you have liver or kidney issues.
• The pill helps achieve and maintain an erection.
• Follow prescribed dosage to avoid complications.
• Not effective as an aphrodisiac without sexual stimulation.
• Avoid using recreational drugs along with vardenafil.
• Regular medical check-ups are recommended during use.

Therefore, M1 accounts for approximately 7% of total pharmacologic activity.ExcretionThe mean terminal half-life of vardenafil in patients receiving vardenafil erectile dysfunction tablets uk 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. 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.

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placebo: 433±109 and 426±105 seconds, respectively; 20 mg vardenafil vs. placebo: 414±114 and 411±124 seconds, respectively). The total time to angina was not altered by vardenafil when compared to placebo (10 mg vardenafil vs. placebo: 291±123 and 292±110 seconds; 20 mg vardenafil vs. placebo: 354±137 and 347±143 seconds, respectively).

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The total time to 1 mm or greater ST-segment depression was similar to placebo in both the 10 mg and the 20 mg vardenafil groups (10 mg vardenafil vs. placebo: 380±108 and 334±108 seconds; 20 mg vardenafil vs. placebo: 364±101 and 366±105 seconds, respectively).Effects on EyeSingle oral doses of phosphodiesterase inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green) using the Farnsworth-Munsell 100-hue (FM-100) test and reductions in electroretinogram (ERG) b-wave amplitudes, with peak effects near the time of peak plasma levels. These findings are consistent with the inhibition of PDE6 in rods and cones, which is involved in phototransduction in the retina. The findings were most evident one hour after administration, diminishing but still present 6 hours after administration. 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. 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 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. Vardenafil may add to the blood pressure lowering effects of antihypertensive agents [see Drug Interactions (7)].

7.3 Effects of Vardenafil on Other Drugs

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.

What should I know about vardenafil before taking it?

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. 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). 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)].

• Vardenafil 10 mg is a selective phosphodiesterase type 5 inhibitor.
• It can improve the ability to achieve an erection.
• Maintain open communication with your healthcare provider.
• Use with caution in elderly patients.
• Report any unusual side effects promptly.
• The medication should not be used recreationally.
• Not recommended for use with certain antihypertensives.
• Effectiveness depends on correct timing and dosage.
• Avoid taking if you have severe liver disease.
• Always read the patient information leaflet.

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.