Label: VARDENAFIL HYDROCHLORIDE tablet

In a single dose study in 25 normal males, vardenafil hydrochloride 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. Two patients on vardenafil in the trial reported episodes of transient cyanopsia (objects appear blue). The pharmacokinetics of vardenafil are approximately dose proportional over the recommended dose range.

Mean vardenafil plasma concentrations measured after the administration of a single oral dose of 20 mg to healthy male volunteers are depicted in Figure 8. Figure 8: Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg Vardenafil Hydrochloride Tablets Dose Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. Two food-effect studies were conducted which showed that high- fat meals caused a reduction in C max by 18%-50%. The mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution. This protein binding is reversible and independent of total drug concentrations.

Before Using

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. 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 best erection pills feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose). Vardenafil trials were not conducted in the pediatric population. In a healthy volunteer study of elderly males (≥65 years) and younger males (18–45 years), mean C max and AUC were 34% and 52% higher, respectively, in the elderly males [see Use in Specific Populations (8.5)].

In volunteers with mild hepatic impairment (Child-Pugh A), the C max and AUC following a 10 mg vardenafil dose were increased by 22% and 17%, respectively, compared to healthy control subjects. [See Dosage and Administration (2.3), Warnings and Precautions (5.8), and Use in Specific Populations (8.6).] In male volunteers with CLcr = 50–80 mL/min, the pharmacokinetics of vardenafil were similar to those observed in a control group with CLcr >80 mL/min.

4.2 Guanylate Cyclase (GC) Stimulators

In a healthy volunteer study of elderly males (≥65 years) and younger males (18–45 years), mean C max and AUC were 34% and 52% higher, respectively, in the elderly males [see Use in Specific Populations (8.5)]. In volunteers with mild hepatic impairment (Child-Pugh A), the C max and AUC following a 10 mg vardenafil dose were increased by 22% and 17%, respectively, compared to healthy control subjects. [See Dosage and Administration (2.3), Warnings and Precautions (5.8), and Use in Specific Populations (8.6).] In male volunteers with CLcr = 50–80 mL/min, the pharmacokinetics of vardenafil were similar to those observed in a control group with CLcr >80 mL/min. [See Dosage and Administration (2.3), Warnings and Precautions (5.9), and Use in Specific Populations (8.7).] 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenesisVardenafil was not carcinogenic in rats and mice when administered daily for 24 months. In these studies systemic drug exposures (AUCs) for unbound (free) vardenafil and its major metabolite were approximately 400- and 170-fold for male and female rats, respectively, and 21- and 37-fold for male and female mice, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 20 mg.MutagenesisVardenafil was not mutagenic as assessed in either the in vitro bacterial Ames assay or the forward mutation assay in Chinese hamster V 79 cells.

Professional resources

Vardenafil was not clastogenic as assessed in either the in vitro chromosomal aberration test or the in vivo mouse micronucleus test.Impairment of FertilityVardenafil did not impair fertility in male and female rats administered doses up to 100 mg/kg/day for 28 days prior to mating in male, and for 14 days prior to mating and through day 7 of gestation in females. In a corresponding 1-month rat toxicity study, this dose produced an AUC value for unbound vardenafil 200 fold greater than AUC in humans at the MRHD of 20 mg. Vardenafil was not carcinogenic in rats and mice when administered daily for 24 months. In these studies systemic drug exposures (AUCs) for unbound (free) vardenafil and its super p force pill major metabolite were approximately 400- and 170-fold for male and female rats, respectively, and 21- and 37-fold for male and female mice, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 20 mg. Vardenafil was not mutagenic as assessed in either the in vitro bacterial Ames assay or the forward mutation assay in Chinese hamster V 79 cells.

Patient resources

Vardenafil did not impair fertility in male and female rats administered doses up to 100 mg/kg/day for 28 days prior to mating in male, and for 14 days prior to mating and through day 7 of gestation in females. 14 CLINICAL STUDIES Vardenafil hydrochloride tablets were evaluated in four major double-blind, randomized, placebo-controlled, fixed-dose, parallel design, multicenter trials in 2431 men aged 20-83 (mean age 57 years; 78% White, 7% Black, 2% Asian, 3% Hispanic and 10% Other/Unknown). The doses of vardenafil hydrochloride tablets in these studies were 5 mg, 10 mg, and 20 mg. Two of these trials were conducted in the general erectile dysfunction (ED) population and two in special ED populations (one in patients with diabetes mellitus and one in post-prostatectomy patients). Vardenafil hydrochloride tablets were dosed without regard to meals on an as needed basis in men with ED, many of whom had multiple other medical conditions. [See Dosage and Administration (2.3), Warnings and Precautions (5.9), and Use in Specific Populations (8.7).] 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenesisVardenafil was not carcinogenic in rats and mice when administered daily for 24 months. In these studies systemic drug exposures (AUCs) for unbound (free) vardenafil and its major metabolite were approximately 400- and 170-fold for male and female rats, respectively, and 21- and 37-fold for male and female mice, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 20 mg.MutagenesisVardenafil was not mutagenic as assessed in either the in vitro bacterial Ames assay or the forward mutation assay in Chinese hamster V 79 cells. Vardenafil was not clastogenic as assessed in either the in vitro chromosomal aberration test or the in vivo mouse micronucleus test.Impairment of FertilityVardenafil did not impair fertility in male and female rats administered doses up to 100 mg/kg/day for 28 days prior to mating in male, and for 14 days prior to mating and through day 7 of gestation in females. In a corresponding 1-month rat toxicity study, this dose produced an AUC value for unbound vardenafil 200 fold greater than AUC in humans at the MRHD of 20 mg.

• Vardenafil interacts with certain blood pressure medicines, affecting efficacy.
• The medication can be used by men of most adult age groups.
• Women who are pregnant or breastfeeding should not use vardenafil.
• It’s advisable to avoid grapefruit or grapefruit juice when on vardenafil.
• Always complete your prescribed course even if symptoms improve.
• Seek medical attention if you notice symptoms of allergic reaction.
• Vardenafil is not intended for use by individuals with recent stroke or heart attack.
• Sexual activity may be dangerous for some men with cardiovascular issues.
• The medication is not approved for use in women or children.
• Use caution when combining vardenafil with other erectile dysfunction drugs.

Vardenafil was not carcinogenic in rats and mice when administered daily for 24 months. In these studies systemic drug exposures (AUCs) for unbound (free) vardenafil and its super p force pill major metabolite were approximately 400- and 170-fold for male and female rats, respectively, and 21- and 37-fold for male and female mice, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 20 mg.

6.2 Postmarketing Experience

The primary endpoints were assessed at 3 months.Primary efficacy assessment in all four major trials was by means of the Erectile Function (EF) Domain score of the validated International Index of Erectile Function (IIEF) Questionnaire and two questions from the Sexual Encounter Profile (SEP) dealing with the ability to achieve vaginal penetration (SEP2), and the ability to maintain an erection long enough for successful intercourse (SEP3).In all four fixed-dose efficacy trials, vardenafil hydrochloride tablets showed clinically meaningful and statistically significant improvement in the EF Domain, SEP2, and SEP3 scores compared to placebo. The mean baseline EF Domain score in these trials was 11.8 (scores range from 0-30 where lower scores represent more severe disease). Vardenafil hydrochloride tablets (5 mg, 10 mg, and 20 mg) were effective in all age categories (<45, 45 to <65, and ≥65 years) and was also effective regardless of race (White, Black, Other).14.1 Trials in a General Erectile Dysfunction PopulationIn the major North American fixed-dose trial, 762 patients (mean age 57, range 20-83 years; 79% White, 13% Black, 4% Hispanic, 2% Asian and 2% Other) were evaluated. The mean baseline EF Domain scores were 13, 13, 13, 14 for the vardenafil hydrochloride tablets 5 mg, 10 mg, 20 mg and placebo groups, respectively. There was significant improvement (p <0.0001) at 3 months with vardenafil hydrochloride tablets (EF Domain scores of 18, 21, 21, for the 5 mg, 10 mg, and 20 mg dose groups, respectively) compared to the placebo group (EF Domain score of 15).

SMILES string

The European trial (total N=803) confirmed these results. The improvement in mean score was maintained at all doses at 6 months in the North American trial.In the North American trial, vardenafil hydrochloride tablets significantly improved the rates of achieving an erection sufficient for penetration (SEP2) at doses of 5 mg, 10 mg, and 20 mg compared to placebo (65%, 75%, and 80%, respectively, compared to a 52% response in the placebo group at 3 months; p <0.0001). The European trial confirmed these results.Vardenafil hydrochloride tablets demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (51% on 5 mg, 64% on 10 mg, and 65% on 20 mg, respectively, compared to 32% on placebo; p <0.0001) at 3 months in the North American trial. This improvement in mean score was maintained at all doses at 6 months in the North American trial.14.2 Trial in Patients with ED and Diabetes MellitusVardenafil hydrochloride tablets demonstrated clinically meaningful and statistically significant improvement in erectile function in a prospective, fixed-dose (10 and 20 mg vardenafil hydrochloride tablets), double-blind, placebo-controlled trial of patients with diabetes mellitus (n=439; mean age 57 years, range 33-81; 80% White, 9% Black, 8% Hispanic, and 3% Other).Significant improvements in the EF Domain were shown in this study (EF Domain scores of 17 on 10 mg vardenafil hydrochloride tablets and 19 on 20 mg vardenafil hydrochloride tablets compared to 13 on placebo; p <0.0001).Vardenafil hydrochloride tablets significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (61% on 10 mg and 64% on 20 mg vardenafil hydrochloride tablets compared to 36% on placebo; p <0.0001).Vardenafil hydrochloride tablets demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (49% on 10 mg, 54% on 20 mg vardenafil hydrochloride tablets compared to 23% on placebo; p <0.0001).14.3 Trial in Patients with ED after Radical ProstatectomyVardenafil hydrochloride tablets demonstrated clinically meaningful and statistically significant improvement in erectile function in a prospective, fixed-dose (10 and 20 mg vardenafil hydrochloride tablets), double-blind, placebo-controlled trial in post-prostatectomy patients (n=427, mean age 60, range 44-77 years; 93% White, 5% Black, 2% Other).Significant improvements in the EF Domain were shown in this study (EF Domain scores of 15 on 10 mg vardenafil hydrochloride tablets and 15 on 20 mg vardenafil hydrochloride tablets compared to 9 on placebo; p <0.0001).Vardenafil hydrochloride tablets significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (47% on 10 mg and 48% on 20 mg vardenafil hydrochloride tablets compared to 22% on placebo; p <0.0001).Vardenafil hydrochloride tablets demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (37% on 10 mg, 34% on 20 mg vardenafil hydrochloride tablets compared to 10% on placebo; p <0.0001).

Incidence not known

Vardenafil was not mutagenic as assessed in either the in vitro bacterial Ames assay or the forward mutation assay in Chinese hamster V 79 cells.

Common side effects of vardenafil

Vardenafil did not impair fertility in male and female rats administered doses up to 100 mg/kg/day for 28 days prior to mating in male, and for 14 days prior to mating and through day 7 of gestation in females. 14 CLINICAL STUDIES Vardenafil hydrochloride tablets were evaluated in four major double-blind, randomized, placebo-controlled, fixed-dose, parallel design, multicenter trials in 2431 men aged 20-83 (mean age 57 years; 78% White, 7% Black, 2% Asian, 3% Hispanic and 10% Other/Unknown). The doses of vardenafil hydrochloride tablets in these studies were 5 mg, 10 mg, and 20 mg.

5.5 Sudden Hearing Loss

In a single dose study in 25 normal males, vardenafil hydrochloride 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. Two patients on vardenafil in the trial reported episodes of transient cyanopsia (objects appear blue). The pharmacokinetics of vardenafil are approximately dose proportional over the recommended dose range. Mean vardenafil plasma concentrations measured after the administration of a single oral dose of 20 mg to healthy male volunteers are depicted in Figure 8.

Biochem/physiol Actions

Figure 8: Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg Vardenafil Hydrochloride Tablets Dose Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. Two food-effect studies were conducted which showed that high- fat meals caused a reduction in C max by 18%-50%. The mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution. This protein binding is reversible and independent of total drug concentrations. 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.

What should I do if I accidentally take too much vardenafil?

Vardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. 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 best erection pills feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose). Vardenafil trials were not conducted in the pediatric population. Two of these trials were conducted in the general erectile dysfunction (ED) population and two in special ED populations (one in patients with diabetes mellitus and one in post-prostatectomy patients).

• Vardenafil HCl 10mg can be effective in treating erectile dysfunction symptoms.
• It’s important to avoid unprescribed or counterfeit versions of the drug.
• Consult a healthcare provider for proper diagnosis before starting treatment.
• Discontinue medication and seek medical help if serious side effects occur.
• The medication’s effects depend on proper timing and dosage adherence.
• It’s safe for most men but always needs individual health assessment.
• Mild side effects may diminish over time or with dose adjustment.
• Use caution with other medications that affect blood pressure or blood flow.
• Do not use vardenafil if you are allergic to similar medications like sildenafil.
• Always inform your doctor of any other medications you are taking.

Vardenafil hydrochloride tablets were dosed without regard to meals on an as needed basis in men with ED, many of whom had multiple other medical conditions. The primary endpoints were assessed at 3 months.Primary efficacy assessment in all four major trials was by means of the Erectile Function (EF) Domain score of the validated International Index of Erectile Function (IIEF) Questionnaire and two questions from the Sexual Encounter Profile (SEP) dealing with the ability to achieve vaginal penetration (SEP2), and the ability to maintain an erection long enough for successful intercourse (SEP3).In all four fixed-dose efficacy trials, vardenafil hydrochloride tablets showed clinically meaningful and statistically significant improvement in the EF Domain, SEP2, and SEP3 scores compared to placebo. The mean baseline EF Domain score in these trials was 11.8 (scores range from 0-30 where lower scores represent more severe disease). Vardenafil hydrochloride tablets (5 mg, 10 mg, and 20 mg) were effective in all age categories (<45, 45 to <65, and ≥65 years) and was also effective regardless of race (White, Black, Other).14.1 Trials in a General Erectile Dysfunction PopulationIn the major North American fixed-dose trial, 762 patients (mean age 57, range 20-83 years; 79% White, 13% Black, 4% Hispanic, 2% Asian and 2% Other) were evaluated.

• Vardenafil 10mg should be used only under medical supervision.
• Overdose may cause serious side effects like priapism or sudden vision loss.
• The medication is available by prescription and not for recreational use.
• Male patients with heart issues should consult a doctor before use.
• Vardenafil may interact with other medications like antibiotics or antifungals.
• Alcohol consumption can increase the risk of side effects when taking vardenafil.
• It’s important to follow the prescribed dosage strictly for safety.
• Use caution if you have liver or kidney problems while taking vardenafil.
• Women and children should avoid using vardenafil, as it's designed for men.
• Discuss all health conditions and medications with your healthcare provider first.

The mean baseline EF Domain scores were 13, 13, 13, 14 for the vardenafil hydrochloride tablets 5 mg, 10 mg, 20 mg and placebo groups, respectively. There was significant improvement (p <0.0001) at 3 months with vardenafil hydrochloride tablets (EF Domain scores of 18, 21, 21, for the 5 mg, 10 mg, and 20 mg dose groups, respectively) compared to the placebo group (EF Domain score of 15). The European trial (total N=803) confirmed these results. The improvement in mean score was maintained at all doses at 6 months in the North American trial.In the North American trial, vardenafil hydrochloride tablets significantly improved the rates of achieving an erection sufficient for penetration (SEP2) at doses of 5 mg, 10 mg, and 20 mg compared to placebo (65%, 75%, and 80%, respectively, compared to a 52% response in the placebo group at 3 months; p <0.0001). The European trial confirmed these results.Vardenafil hydrochloride tablets demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (51% on 5 mg, 64% on 10 mg, and 65% on 20 mg, respectively, compared to 32% on placebo; p <0.0001) at 3 months in the North American trial.

• Vardenafil HCl 10mg can be an effective treatment when used responsibly.
• Always follow the prescribed dosing schedule for safety and efficacy.
• The medication may need to be adjusted based on individual response.
• Use with caution if you have a history of cardiovascular disease.
• Discuss all current medications with your doctor to avoid interactions.
• Vardenafil is not recommended for use by women or children.
• Be aware of possible side effects and seek medical help when needed.
• Alcohol and fatty foods can interfere with the drug’s performance.
• Proper sexual stimulation is required for the drug to work effectively.
• Regular follow-up with your healthcare provider is encouraged.

This improvement in mean score was maintained at all doses at 6 months in the North American trial.14.2 Trial in Patients with ED and Diabetes MellitusVardenafil hydrochloride tablets demonstrated clinically meaningful and statistically significant improvement in erectile function in a prospective, fixed-dose (10 and 20 mg vardenafil hydrochloride tablets), double-blind, placebo-controlled trial of patients with diabetes mellitus (n=439; mean age 57 years, range 33-81; 80% White, 9% Black, 8% Hispanic, and 3% Other).Significant improvements in the EF Domain were shown in this study (EF Domain scores of 17 on 10 mg vardenafil hydrochloride tablets and 19 on 20 mg vardenafil hydrochloride tablets compared to 13 on placebo; p <0.0001).Vardenafil hydrochloride tablets significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (61% on 10 mg and 64% on 20 mg vardenafil hydrochloride tablets compared to 36% on placebo; p <0.0001).Vardenafil hydrochloride tablets demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (49% on 10 mg, 54% on 20 mg vardenafil hydrochloride tablets compared to 23% on placebo; p <0.0001).14.3 Trial in Patients with ED after Radical ProstatectomyVardenafil hydrochloride tablets demonstrated clinically meaningful and statistically significant improvement in erectile function in a prospective, fixed-dose (10 and 20 mg vardenafil hydrochloride tablets), double-blind, placebo-controlled trial in post-prostatectomy patients (n=427, mean age 60, range 44-77 years; 93% White, 5% Black, 2% Other).Significant improvements in the EF Domain were shown in this study (EF Domain scores of 15 on 10 mg vardenafil hydrochloride tablets and 15 on 20 mg vardenafil hydrochloride tablets compared to 9 on placebo; p <0.0001).Vardenafil hydrochloride tablets significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (47% on 10 mg and 48% on 20 mg vardenafil hydrochloride tablets compared to 22% on placebo; p <0.0001).Vardenafil hydrochloride tablets demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (37% on 10 mg, 34% on 20 mg vardenafil hydrochloride tablets compared to 10% on placebo; p <0.0001).

Unser Haus