Label: SILDENAFIL CITRATE tablet

Blood pressure was measured after administration of sildenafil at the same times as those specified for the first doxazosin study. There were no severe adverse events potentially related to blood pressure and no episodes of syncope reported in this study. The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 100 mg sildenafil or matching placebo are shown in Figure 4.

• The pill’s active ingredient, sildenafil citrate, is classified as a PDE5 inhibitor.
• PDE5 inhibitors help relax blood vessels and improve blood flow.
• They are most effective when combined with sexual arousal.

Blood pressure was measured after administration of sildenafil at the same times as those specified for the previous doxazosin studies.

Proper Use

The patient addressed both questions at the final visit for the last 4 weeks of the study. The possible categorical responses to these questions were (0) no attempted intercourse, (1) never or almost never, (2) a few times, (3) sometimes, (4) most times, and (5) almost always or always. Also collected as part of the IIEF was information about other aspects of sexual function, including information on erectile function, orgasm, desire, satisfaction with intercourse, and overall sexual satisfaction. Sexual function data were also recorded by patients sildenafil 130mg in a daily diary. In addition, patients were asked a global efficacy question and an optional partner questionnaire was administered.Efficacy Results from Controlled Clinical StudiesThe effect on one of the major end points, maintenance of erections after penetration, is shown in Figure 6, for the pooled results of 5 fixed-dose, dose-response studies of greater than one month duration, showing response according to baseline function.

Marketing and sales

Results with all doses have been pooled, but scores showed greater improvement at the 50 and 100 mg doses than at 25 mg. The pattern of responses was similar for the other principal question, the ability to achieve an erection sufficient for intercourse. The titration studies, in which most patients received 100 mg, showed similar results. Figure 6 shows that regardless of the baseline levels of function, subsequent function in patients treated with sildenafil was better than that seen in patients treated with placebo. At the same time, on-treatment function was better in treated patients who were less impaired at baseline.Figure 6. There were no episodes of syncope reported in this study. In a double-blind study, 144 patients with erectile dysfunction and chronic stable angina limited by exercise, not receiving chronic oral nitrates, were randomized to a single dose of placebo or sildenafil 100 mg 1 hour prior to exercise testing. These results demonstrated that the effect of sildenafil on the primary endpoint was statistically non-inferior to placebo. Sildenafil is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (range 25-63%). Both sildenafil and the metabolite have terminal half lives of sildenafil 50 mg india about 4 hours. Absorption and Distribution: Sildenafil is rapidly absorbed. Protein binding is independent of total drug concentrations. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenesisSildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 20- and 38- times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg.

Product	Dosage	Quantity + Bonus	Price
Kamagra Oral Jelly	100mg	63 + 7 Sachets	224.18€ 213.50€	Buy
Viagra Generic	25mg	10 Pills	25.19€ 23.99€	Buy
Viagra Generic	200mg	20 Pills	61.69€ 58.75€	Buy
Kamagra	100mg	60 + 4 Pills	201.34€ 191.75€	Buy
Viagra Generic	50mg	10 Pills	26.87€ 25.59€	Buy
Viagra Generic	150mg	120 + 8 Pills	177.58€ 169.12€	Buy
Viagra Generic	200mg	60 + 4 Pills	125.19€ 119.23€	Buy
Viagra Generic	150mg	90 + 6 Pills	147.18€ 140.17€	Buy
Kamagra	100mg	120 + 6 Pills	330.74€ 314.99€	Buy
Kamagra Oral Jelly	100mg	110 + 9 Sachets	334.87€ 318.92€	Buy
Kamagra Oral Jelly	100mg	30 + 5 Sachets	136.20€ 129.71€	Buy
Kamagra Soft Tabs	100mg	60 + 4 Pills	180.59€ 171.99€	Buy

Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.4 times the MRHD on a mg/m 2basis in a 50 kg subject.MutagenesisSildenafil was negative in in vitrobacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitrohuman lymphocytes and in vivomouse micronucleus assays to detect clastogenicity.Impairment of FertilityThere was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC. 14 CLINICAL STUDIES In clinical studies, sildenafil was assessed for its effect on the ability of men with erectile dysfunction (ED) to engage in sexual activity and in many cases specifically on the ability to achieve and maintain an erection sufficient for satisfactory sexual activity. Sildenafil was evaluated primarily at doses of 25 mg, 50 mg and 100 mg in 21 randomized, double-blind, placebo-controlled trials of up to 6 months in duration, using a variety of study designs (fixed dose, titration, parallel, crossover).

5.8 Effects on Bleeding

As in the other titration studies, patients were started on 50 mg and allowed to adjust the dose up to 100 mg or down to 25 mg of sildenafil; all patients, however, were receiving 50 mg or 100 mg at the end of the study. There were highly statistically significant improvements on the two principal IIEF questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) on sildenafil compared to placebo. On a global improvement question, 57% of sildenafil patients reported improved erections versus 10% on placebo. Diary data indicated that on sildenafil, 48% of intercourse attempts were successful versus 12% on placebo.One randomized, double-blind, placebo-controlled, crossover, flexible-dose (up to 100 mg) study of patients with erectile dysfunction resulting from spinal cord injury (n=178) was conducted. The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of sildenafil.

Your questions answered

On a global improvement question, 83% of patients reported improved erections on sildenafil versus 12% on placebo. Diary data indicated that on sildenafil, 59% of attempts at sexual intercourse were successful compared to 13% on placebo.Across all trials, sildenafil improved the erections of 43% of radical prostatectomy patients compared to 15% on placebo.Subgroup analyses of responses to a global improvement question in patients with psychogenic etiology in two fixed-dose studies (total n=179) and two titration studies (total n=149) showed 84% of sildenafil patients reported improvement in erections compared with 26% of placebo. Sildenafil was administered to more than 3,000 patients aged 19 to 87 years, with ED of various etiologies (organic, psychogenic, mixed) with a mean duration of 5 years. Sildenafil demonstrated statistically significant improvement compared to placebo in all 21 studies. The studies that established benefit demonstrated improvements in success rates for sexual intercourse compared with placebo.Efficacy Endpoints in Controlled Clinical StudiesThe effectiveness of sildenafil was evaluated in most studies using several assessment instruments. The primary measure in the principal studies was a sexual function questionnaire (the International Index of Erectile Function-IIEF) administered during a 4-week treatment-free run-in period, at baseline, at follow-up visits, and at the end of double-blind, placebo-controlled, at-home treatment. Two of the questions from the IIEF served as primary study endpoints; categorical responses were elicited to questions about (1) the ability to achieve erections sufficient for sexual intercourse and (2) the maintenance of erections after penetration.

Drug Class	Interaction Effect
Nitrates	Severe hypotension
Alpha-blockers	Increased risk of hypotension
CYP3A4 inhibitors	Increased sildenafil levels, risk of side effects
Other PDE5 inhibitors	Increased risk of adverse effects

The patient addressed both questions at the final visit for the last 4 weeks of the study. The possible categorical responses to these questions were (0) no attempted intercourse, (1) never or almost never, (2) a few times, (3) sometimes, (4) most times, and (5) almost always or always. Also collected as part of the IIEF was information about other aspects of sexual function, including information on erectile function, orgasm, desire, satisfaction with intercourse, and overall sexual satisfaction.

• Sildenafil is often used off-label for pulmonary hypertension under medical supervision.
• The dosage for pulmonary use may differ from the 100mg standard.
• Always follow healthcare provider instructions for different conditions.

Sexual function data were also recorded by patients sildenafil 130mg in a daily diary. In addition, patients were asked a global efficacy question and an optional partner questionnaire was administered.Efficacy Results from Controlled Clinical StudiesThe effect on one of the major end points, maintenance of erections after penetration, is shown in Figure 6, for the pooled results of 5 fixed-dose, dose-response studies of greater than one month duration, showing response according to baseline function. Results with all doses have been pooled, but scores showed greater improvement at the 50 and 100 mg doses than at 25 mg. The pattern of responses was similar for the other principal question, the ability to achieve an erection sufficient for intercourse. The titration studies, in which most patients received 100 mg, showed similar results. Figure 6 shows that regardless of the baseline levels of function, subsequent function in patients treated with sildenafil was better than that seen in patients treated with placebo. At the same time, on-treatment function was better in treated patients who were less impaired at baseline.Figure 6. Effect of sildenafil and Placebo on Maintenance of Erection by Baseline Score.The frequency of patients reporting improvement of erections in response to a global question in four of the randomized, double-blind, parallel, placebo-controlled fixed dose studies (1797 patients) of 12 to 24 weeks duration is shown in Figure 7.

• The blue sildenafil pill is not intended for use by women or children.
• It does not cure erectile dysfunction but helps manage symptoms temporarily.
• Lifestyle factors, such as exercise and diet, can also influence erectile health.

These patients had erectile dysfunction at baseline that was characterized by median categorical scores of 2 (a few times) on principal IIEF questions.

Overdose/Missed Dose

Effect of sildenafil and Placebo on Maintenance of Erection by Baseline Score.The frequency of patients reporting improvement of erections in response to a global question in four of the randomized, double-blind, parallel, placebo-controlled fixed dose studies (1797 patients) of 12 to 24 weeks duration is shown in Figure 7. These patients had erectile dysfunction at baseline that was characterized by median categorical scores of 2 (a few times) on principal IIEF questions. Erectile dysfunction was attributed to organic (58%; generally not characterized, but including diabetes and excluding spinal cord injury), psychogenic (17%), or mixed (24%) etiologies. Sixty-three percent, 74%, and 82% of the patients on 25 mg, 50 mg and 100 mg of sildenafil, respectively, reported an improvement in their erections, compared to 24% on placebo. In the titration studies (n=644) (with most patients eventually receiving 100 mg), results were similar.Overall treatment p<0.0001Figure 7.

Erectile dysfunction

Percentage of Patients Reporting an Improvement in Erections.The patients in studies had varying degrees of ED. One-third to one-half of the subjects in sildenafil 100g these studies reported successful intercourse at least once during a 4-week, treatment-free run-in period.In many of the studies, of both fixed dose and titration designs, daily diaries were kept by patients. In these studies, involving about 1600 patients, analyses of patient diaries showed no effect of sildenafil on rates of attempted intercourse (about 2 per week), but there was clear treatment-related improvement in sexual function: per patient weekly success rates averaged 1.3 on 50-100 mg of sildenafil vs 0.4 on placebo; similarly, group mean success rates (total successes divided by total attempts) were about 66% on sildenafil vs about 20% on placebo.During 3 to 6 months of double-blind treatment or longer-term (1 year), open-label studies, few patients withdrew from active treatment for any reason, including lack of effectiveness. At the end of the long-term study, 88% of patients reported that sildenafil improved their erections.Men with untreated ED had relatively low baseline scores for all aspects of sexual function measured (again using a 5-point scale) in the IIEF. Sildenafil improved these aspects of sexual function: frequency, firmness and maintenance of erections; frequency of orgasm; frequency and level of desire; frequency, satisfaction and enjoyment of intercourse; and overall relationship satisfaction.One randomized, double-blind, flexible-dose, placebo-controlled study included only patients with erectile dysfunction attributed to complications of diabetes mellitus (n=268). Erectile dysfunction was attributed to organic (58%; generally not characterized, but including diabetes and excluding spinal cord injury), psychogenic (17%), or mixed (24%) etiologies. Sixty-three percent, 74%, and 82% of the patients on 25 mg, 50 mg and 100 mg of sildenafil, respectively, reported an improvement in their erections, compared to 24% on placebo.

Condition	Explanation
Nitrate Use	Avoid due to risk of severe hypotension
Heart Conditions	Caution in unstable angina or recent MI
Retinal Disorders	Caution, especially in hereditary degenerations
Allergies	Do not use if allergic to sildenafil or related drugs

In the titration studies (n=644) (with most patients eventually receiving 100 mg), results were similar.Overall treatment p<0.0001Figure 7. Percentage of Patients Reporting an Improvement in Erections.The patients in studies had varying degrees of ED. One-third to one-half of the subjects in sildenafil 100g these studies reported successful intercourse at least once during a 4-week, treatment-free run-in period.In many of the studies, of both fixed dose and titration designs, daily diaries were kept by patients.

7.4 Ritonavir and other CYP3A4 inhibitors

In these studies, involving about 1600 patients, analyses of patient diaries showed no effect of sildenafil on rates of attempted intercourse (about 2 per week), but there was clear treatment-related improvement in sexual function: per patient weekly success rates averaged 1.3 on 50-100 mg of sildenafil vs 0.4 on placebo; similarly, group mean success rates (total successes divided by total attempts) were about 66% on sildenafil vs about 20% on placebo.During 3 to 6 months of double-blind treatment or longer-term (1 year), open-label studies, few patients withdrew from active treatment for any reason, including lack of effectiveness. At the end of the long-term study, 88% of patients reported that sildenafil improved their erections.Men with untreated ED had relatively low baseline scores for all aspects of sexual function measured (again using a 5-point scale) in the IIEF. Sildenafil improved these aspects of sexual function: frequency, firmness and maintenance of erections; frequency of orgasm; frequency and level of desire; frequency, satisfaction and enjoyment of intercourse; and overall relationship satisfaction.One randomized, double-blind, flexible-dose, placebo-controlled study included only patients with erectile dysfunction attributed to complications of diabetes mellitus (n=268). As in the other titration studies, patients were started on 50 mg and allowed to adjust the dose up to 100 mg or down to 25 mg of sildenafil; all patients, however, were receiving 50 mg or 100 mg at the end of the study.

5.3 Effects on the Eye

Protein binding is independent of total drug concentrations. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenesisSildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 20- and 38- times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg. Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.4 times the MRHD on a mg/m 2basis in a 50 kg subject.MutagenesisSildenafil was negative in in vitrobacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitrohuman lymphocytes and in vivomouse micronucleus assays to detect clastogenicity.Impairment of FertilityThere was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC. 14 CLINICAL STUDIES In clinical studies, sildenafil was assessed for its effect on the ability of men with erectile dysfunction (ED) to engage in sexual activity and in many cases specifically on the ability to achieve and maintain an erection sufficient for satisfactory sexual activity. Sildenafil was evaluated primarily at doses of 25 mg, 50 mg and 100 mg in 21 randomized, double-blind, placebo-controlled trials of up to 6 months in duration, using a variety of study designs (fixed dose, titration, parallel, crossover).

How should I store sildenafil?

Sildenafil was administered to more than 3,000 patients aged 19 to 87 years, with ED of various etiologies (organic, psychogenic, mixed) with a mean duration of 5 years. Sildenafil demonstrated statistically significant improvement compared to placebo in all 21 studies. The studies that established benefit demonstrated improvements in success rates for sexual intercourse compared with placebo.Efficacy Endpoints in Controlled Clinical StudiesThe effectiveness of sildenafil was evaluated in most studies using several assessment instruments. The primary measure in the principal studies was a sexual function questionnaire (the International Index of Erectile Function-IIEF) administered during a 4-week treatment-free run-in period, at baseline, at follow-up visits, and at the end of double-blind, placebo-controlled, at-home treatment. Two of the questions from the IIEF served as primary study endpoints; categorical responses were elicited to questions about (1) the ability to achieve erections sufficient for sexual intercourse and (2) the maintenance of erections after penetration. There were highly statistically significant improvements on the two principal IIEF questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) on sildenafil compared to placebo. On a global improvement question, 57% of sildenafil patients reported improved erections versus 10% on placebo. Diary data indicated that on sildenafil, 48% of intercourse attempts were successful versus 12% on placebo.One randomized, double-blind, placebo-controlled, crossover, flexible-dose (up to 100 mg) study of patients with erectile dysfunction resulting from spinal cord injury (n=178) was conducted. The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of sildenafil.

5.4 Hearing Loss

On a global improvement question, 83% of patients reported improved erections on sildenafil versus 12% on placebo.

8.4 Pediatric Use

Blood pressure was measured after administration of sildenafil at the same times as those specified for the first doxazosin study. There were no severe adverse events potentially related to blood pressure and no episodes of syncope reported in this study. The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 100 mg sildenafil or matching placebo are shown in Figure 4. Blood pressure was measured after administration of sildenafil at the same times as those specified for the previous doxazosin studies. There were no episodes of syncope reported in this study.

Who should not take sildenafil?

In a double-blind study, 144 patients with erectile dysfunction and chronic stable angina limited by exercise, not receiving chronic oral nitrates, were randomized to a single dose of placebo or sildenafil 100 mg 1 hour prior to exercise testing. These results demonstrated that the effect of sildenafil on the primary endpoint was statistically non-inferior to placebo. Sildenafil is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (range 25-63%). Both sildenafil and the metabolite have terminal half lives of sildenafil 50 mg india about 4 hours. Absorption and Distribution: Sildenafil is rapidly absorbed. Diary data indicated that on sildenafil, 59% of attempts at sexual intercourse were successful compared to 13% on placebo.Across all trials, sildenafil improved the erections of 43% of radical prostatectomy patients compared to 15% on placebo.Subgroup analyses of responses to a global improvement question in patients with psychogenic etiology in two fixed-dose studies (total n=179) and two titration studies (total n=149) showed 84% of sildenafil patients reported improvement in erections compared with 26% of placebo.