Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil’s pharmacologic effects. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).

Brand Name	Manufacturer	Country of Origin	Description
Viagra	Pfizer	USA	Most well-known brand
Revatio	Pfizer	USA	Used for pulmonary hypertension
Sildenafil ZYDUS	Zydus Cadila	India	Generic alternative
Sildenafil Mylan	Mylan Pharmaceuticals	USA	Generic options

Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach. Geriatrics:Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18 to 45 years).

Full Prescribing Information

A tablet sildenafil 50 mg starting oral dose of 25 mg should be considered in those patients [ see Dosage and Administration (2.5)]. Effects of Other Drugs on Sildenafil citrate Sildenafil metabolism is principally mediated by CYP3A4 (major route) and CYP2C9 (minor route). Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil citrate (50 mg) to healthy volunteers. When a single 100 mg dose of sildenafil citrate was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 160% increase in sildenafil C maxand a 182% increase in sildenafil AUC. Population pharmacokinetic data from patients in clinical trials also indicated a reduction in sildenafil clearance when it was co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) [ see Dosage and Administration (2.4)and Drug Interactions (7.4)].

Phosphodiesterase-5 inhibitors

In another study in healthy male volunteers, co-administration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with sildenafil citrate (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil C maxand a 1000% (11-fold) increase in sildenafil plasma AUC. Sildenafil citrate had no effect on ritonavir pharmacokinetics [ see Dosage and Administration (2.4)and Drug Interactions (7.4)]. Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels. In a study of healthy male volunteers, co-administration of sildenafil at steady state (80 mg t.i.d.) with endothelin receptor antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) at steady state (125 mg b.i.d.) resulted in a 63% decrease of sildenafil AUC and a 55% decrease in sildenafil C max. Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma levels of sildenafil. Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [ see Dosage and Administration (2.5), and Use in Specific Populations (8.5)] Renal Impairment:In volunteers with mild (CLcr=50 to 80 mL/min) and moderate (CLcr=30 to 49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil citrate (50 mg) were not altered.

Product	Dosage	Quantity + Bonus	Price
Kamagra Polo	100mg	20 Pills	83.56€ 79.58€	Buy
Kamagra Soft Tabs	100mg	180 + 8 Pills	425.45€ 405.19€	Buy
Viagra Generic	100mg	90 + 6 Pills	129.02€ 122.88€	Buy
Viagra Generic	50mg	90 + 6 Pills	107.37€ 102.26€	Buy
Kamagra Soft Tabs	100mg	20 Pills	79.79€ 75.99€	Buy
Viagra Generic	25mg	10 Pills	25.19€ 23.99€	Buy
Kamagra Polo	100mg	180 + 8 Pills	446.52€ 425.26€	Buy
Viagra Generic	50mg	10 Pills	26.87€ 25.59€	Buy
Viagra Generic	50mg	360 + 10 Pills	225.33€ 214.60€	Buy
Kamagra Polo	100mg	272 + 12 Pills	622.94€ 593.28€	Buy
Kamagra Oral Jelly	100mg	220 + 18 Sachets	662.24€ 630.70€	Buy
Viagra Generic	150mg	270 + 10 Pills	326.61€ 311.06€	Buy
Viagra Generic	25mg	90 + 6 Pills	105.03€ 100.03€	Buy

In volunteers with severe (CLcr <30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC and C maxcompared to age-matched volunteers with no renal impairment [ see Dosage and Administration (2.5), and Use in Specific Populations (8.6)]. In addition, N-desmethyl metabolite AUC and C maxvalues significantly increased by 200% and 79%, respectively in subjects with severe renal impairment compared to subjects with normal renal function. Hepatic Impairment:In volunteers with hepatic impairment (Child-Pugh Class A and B), sildenafil clearance was reduced, resulting in increases in AUC (85%) and C max(47%) compared to age-matched volunteers with no hepatic impairment. The pharmacokinetics of sildenafil in patients with severely impaired hepatic function (Child-Pugh Class C) have not been studied [ see Dosage and Administration (2.5), and Use in Specific Populations (8.7)]. Therefore, age >65, hepatic impairment and severe renal impairment are associated with increased plasma levels of sildenafil.

Related Products

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 to 21 months sildenafil tablets lp 100 mg at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.4 times the MRHD on a mg/m2 basis in a 50 kg subject. Sildenafil 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 to 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/m2 basis in a 50 kg subject. 14 CLINICAL STUDIES In clinical studies, sildenafil citrate 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.

How is sildenafil supplied (dosage forms)?

Sildenafil citrate 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). Sildenafil citrate 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 citrate 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 citrate 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. A tablet sildenafil 50 mg starting oral dose of 25 mg should be considered in those patients [ see Dosage and Administration (2.5)]. Effects of Other Drugs on Sildenafil citrate Sildenafil metabolism is principally mediated by CYP3A4 (major route) and CYP2C9 (minor route). Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil citrate (50 mg) to healthy volunteers. When a single 100 mg dose of sildenafil citrate was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 160% increase in sildenafil C maxand a 182% increase in sildenafil AUC. Population pharmacokinetic data from patients in clinical trials also indicated a reduction in sildenafil clearance when it was co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) [ see Dosage and Administration (2.4)and Drug Interactions (7.4)].

• Sildenafil tablets are classified as phosphodiesterase inhibitors.
• They are quick-acting but effects vary by individual.
• Avoid taking with other erectile dysfunction medications.
• Liver or kidney impairment may require dose adjustments.
• Do not use sildenafil during sexual activity if unadvised.
• Safe sexual activity involves knowing your health status.
• Window for maximum effectiveness is around 1 hour before.
• Avoid excessive physical exertion after taking sildenafil.

In another study in healthy male volunteers, co-administration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with sildenafil citrate (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil C maxand a 1000% (11-fold) increase in sildenafil plasma AUC. Sildenafil citrate had no effect on ritonavir pharmacokinetics [ see Dosage and Administration (2.4)and Drug Interactions (7.4)]. Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels. In a study of healthy male volunteers, co-administration of sildenafil at steady state (80 mg t.i.d.) with endothelin receptor antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) at steady state (125 mg b.i.d.) resulted in a 63% decrease of sildenafil AUC and a 55% decrease in sildenafil C max. Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma levels of sildenafil. Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil citrate.

Step	Description	Notes
Consult a healthcare provider	Discuss suitability and health conditions	Important before use
Dose administration	Take with a glass of water, 30-60 min before activity	Avoid heavy or fatty meals
Frequency	Do not exceed once per day	Follow prescribed instructions
Food interactions	Fatty meals may delay absorption	Better taken on an empty stomach or light meal

In healthy male volunteers, there was no evidence of a clinically significant effect of azithromycin (500 mg daily for 3 days) on the systemic exposure of sildenafil or its major circulating metabolite. Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. These effects on the metabolite are not expected to be of clinical consequence.

• For best results, take sildenafil on an empty stomach.
• Eating fatty foods may delay its onset.
• The medication should be taken approximately 30 minutes before activity.
• Do not double dose to compensate for missed doses.
• Keep regular medical appointments during treatment.
• Report any worsening of symptoms to your doctor.
• Never use sildenafil if experiencing chest pain without medical guidance.
• Always follow the prescribed health regimen.

Effects of Sildenafil citrate on Other Drugs Sildenafil is a weak inhibitor of the CYP isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 µM). Given sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that sildenafil citrate will alter the clearance of substrates of these isoenzymes. No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), sildenafil oral solution both of which are metabolized by CYP2C9. In a study of healthy male volunteers, sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.

Region	Average Cost per Pack	Pack Quantity	Notes
USA	$30 - $50	30 tablets	Generic versions available
UK	£15 - £25	30 tablets	Prescribed or OTC in some areas
India	₹150 - ₹300	10-30 tablets	Widely available, generic options
Australia	AUD 40 - AUD 70	30 tablets	Prescription required

Sildenafil citrate (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg). Sildenafil at steady state, at a dose not approved for the treatment of erectile dysfunction (80 mg t.i.d.) resulted in a 50% increase in AUC and a 42% increase in C maxof bosentan (125 mg b.i.d.).

2.3 Dosage Adjustments in Specific Situations

Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil citrate. In healthy male volunteers, there was no evidence of a clinically significant effect of azithromycin (500 mg daily for 3 days) on the systemic exposure of sildenafil or its major circulating metabolite. Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. These effects on the metabolite are not expected to be of clinical consequence. Effects of Sildenafil citrate on Other Drugs Sildenafil is a weak inhibitor of the CYP isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 µM).

Dosage for erectile dysfunction (ED)

Given sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that sildenafil citrate will alter the clearance of substrates of these isoenzymes. No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), sildenafil oral solution both of which are metabolized by CYP2C9. In a study of healthy male volunteers, sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates. Sildenafil citrate (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg). Sildenafil at steady state, at a dose not approved for the treatment of erectile dysfunction (80 mg t.i.d.) resulted in a 50% increase in AUC and a 42% increase in C maxof bosentan (125 mg b.i.d.). 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 to 21 months sildenafil tablets lp 100 mg at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.4 times the MRHD on a mg/m2 basis in a 50 kg subject.

5.6 Combination with other PDE-5 Inhibitors

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. 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 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.

8.2 Lactation

Sildenafil 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 to 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/m2 basis in a 50 kg subject. 14 CLINICAL STUDIES In clinical studies, sildenafil citrate 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 citrate 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).

5.5 Hypotension when Co-administered with Alpha-blockers or Anti-hypertensives

Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil’s pharmacologic effects. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach. Geriatrics:Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18 to 45 years). Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [ see Dosage and Administration (2.5), and Use in Specific Populations (8.5)] Renal Impairment:In volunteers with mild (CLcr=50 to 80 mL/min) and moderate (CLcr=30 to 49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil citrate (50 mg) were not altered.

Does sildenafil interact with foods or drinks?

In volunteers with severe (CLcr <30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC and C maxcompared to age-matched volunteers with no renal impairment [ see Dosage and Administration (2.5), and Use in Specific Populations (8.6)]. In addition, N-desmethyl metabolite AUC and C maxvalues significantly increased by 200% and 79%, respectively in subjects with severe renal impairment compared to subjects with normal renal function. Hepatic Impairment:In volunteers with hepatic impairment (Child-Pugh Class A and B), sildenafil clearance was reduced, resulting in increases in AUC (85%) and C max(47%) compared to age-matched volunteers with no hepatic impairment. The pharmacokinetics of sildenafil in patients with severely impaired hepatic function (Child-Pugh Class C) have not been studied [ see Dosage and Administration (2.5), and Use in Specific Populations (8.7)]. Therefore, age >65, hepatic impairment and severe renal impairment are associated with increased plasma levels of sildenafil. Sildenafil citrate 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 citrate 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 citrate 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. 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.

• Sildenafil tablets 125 mg are often prescribed for pulmonary hypertension.
• The dosage can vary depending on the condition.
• It’s important to maintain open communication with your doctor.
• Alcohol consumption can impair sildenafil’s effectiveness.
• Avoid driving if you experience dizziness or vision problems.
• Use sildenafil exactly as prescribed to avoid complications.
• Do not share medication with others.
• Regular medical check-ups are recommended during use.

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 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.